Dose-effect relationships for fife shortening, tumorigenesis, and systemic injuries in mice irradiated with fission neutron or 60Co gamma radiation

International Nuclear Information System (INIS)

Ainsworth, E.J.; Fry, R.J.M.; Williamson, F.S.; Brennan, P.C.; Stearner, S.P.; Yang, V.V.; Crouse, D.A.; Rust, J.H.; Borak, T.B.

1977-01-01

The objective of this research is to provide additional data on life shortening, neoplastic and non-neoplastic diseases, and other systematic injuries necessary for the determination of dose-response relationships. The data are used to test existing predictive models and formulate new models which may assist with radiation risk assessment. Late somatic effects of fission neutrons from the JANUS reactor or from cobalt-60 gamma radiation are evaluated in young adult B6CF 1 mice that receive either a range of single doses or protracted doses at low dose rates; the protracted irradiation is administered over a 6-month period. After single doses of gamma radiation the relationship between radiation dose and percent life shortening appears linear whereas after single doses of fission spectrum neutrons a non-linear dose response is observed. These results suggest that estimates of radiation risk for fission spectrum neutrons should take into account the following: the curvilinearity of the neutron dose-response curve for life shortening, and the increased life shortening produced by neutron dose fractionation

Estimation of radiation risks at low dose

International Nuclear Information System (INIS)

1990-04-01

The report presents a review of the effects caused by radiation in low doses, or at low dose rates. For the inheritable (or ''genetic''), as well as for the cancer producing effects of radiation, present evidence is consistent with: (a) a non-linear relationship between the frequency of at least some forms of these effects, with comparing frequencies caused by doses many times those received annually from natural sources, with those caused by lower doses; (b) a probably linear relationship, however, between dose and frequency of effects for dose rates in the region of that received from natural sources, or at several times this rate; (c) no evidence to indicate the existence of a threshold dose below which such effects are not produced, and a strong inference from the mode of action of radiation on cells at low dose rates that no such thresholds are likely to apply to the detrimental, cancer-producing or inheritable, effects resulting from unrepaired damage to single cells. 19 refs

The Dose Response Relationship for Radiation Carcinogenesis

Science.gov (United States)

Hall, Eric

2008-03-01

Recent surveys show that the collective population radiation dose from medical procedures in the U.S. has increased by 750% in the past two decades. It would be impossible to imagine the practice of medicine today without diagnostic and therapeutic radiology, but nevertheless the widespread and rapidly increasing use of a modality which is a known human carcinogen is a cause for concern. To assess the magnitude of the problem it is necessary to establish the shape of the dose response relationship for radiation carcinogenesis. Information on radiation carcinogenesis comes from the A-bomb survivors, from occupationally exposed individuals and from radiotherapy patients. The A-bomb survivor data indicates a linear relationship between dose and the risk of solid cancers up to a dose of about 2.5 Sv. The lowest dose at which there is a significant excess cancer risk is debatable, but it would appear to be between 40 and 100 mSv. Data from the occupation exposure of nuclear workers shows an excess cancer risk at an average dose of 19.4 mSv. At the other end of the dose scale, data on second cancers in radiotherapy patients indicates that cancer risk does not continue to rise as a linear function of dose, but tends towards a plateau of 40 to 60 Gy, delivered in a fractionated regime. These data can be used to estimate the impact of diagnostic radiology at the low dose end of the dose response relationship, and the impact of new radiotherapy modalities at the high end of the dose response relationship. In the case of diagnostic radiology about 90% of the collective population dose comes from procedures (principally CT scans) which involve doses at which there is credible evidence of an excess cancer incidence. While the risk to the individual is small and justified in a symptomatic patient, the same is not true of some screening procedures is asymptomatic individuals, and in any case the huge number of procedures must add up to a potential public health problem. In the

Youth suicide attempts and the dose-response relationship to parental risk factors: a population-based study

DEFF Research Database (Denmark)

Christiansen, E; Goldney, R D; Beautrai, A L

2011-01-01

BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suic......BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...

The risk of low doses of ionising radiation and the linear no threshold relationship debate

International Nuclear Information System (INIS)

Tubiana, M.; Masse, R.; Vathaire, F. de; Averbeck, D.; Aurengo, A.

2007-01-01

The ICRP and the B.E.I.R. VII reports recommend a linear no threshold (L.N.T.) relationship for the estimation of cancer excess risk induced by ionising radiations (IR), but the 2005 report of Medicine and Science French Academies concludes that it leads to overestimate of risk for low and very low doses. The bases of L.N.T. are challenged by recent biological and animal experimental studies which show that the defence against IR involves the cell microenvironment and the immunologic system. The defence mechanisms against low doses are different and comparatively more effective than for high doses. Cell death is predominant against low doses. DNA repairing is activated against high doses, in order to preserve tissue functions. These mechanisms provide for multicellular organisms an effective and low cost defence system. The differences between low and high doses defence mechanisms are obvious for alpha emitters which show several greys threshold effects. These differences result in an impairment of epidemiological studies which, for statistical power purpose, amalgamate high and low doses exposure data, since it would imply that cancer IR induction and defence mechanisms are similar in both cases. Low IR dose risk estimates should rely on specific epidemiological studies restricted to low dose exposures and taking precisely into account potential confounding factors. The preliminary synthesis of cohort studies for which low dose data (< 100 mSv) were available show no significant risk excess, neither for solid cancer nor for leukemias. (authors)

An update on modeling dose-response relationships: Accounting for correlated data structure and heterogeneous error variance in linear and nonlinear mixed models.

Science.gov (United States)

Gonçalves, M A D; Bello, N M; Dritz, S S; Tokach, M D; DeRouchey, J M; Woodworth, J C; Goodband, R D

2016-05-01

Advanced methods for dose-response assessments are used to estimate the minimum concentrations of a nutrient that maximizes a given outcome of interest, thereby determining nutritional requirements for optimal performance. Contrary to standard modeling assumptions, experimental data often present a design structure that includes correlations between observations (i.e., blocking, nesting, etc.) as well as heterogeneity of error variances; either can mislead inference if disregarded. Our objective is to demonstrate practical implementation of linear and nonlinear mixed models for dose-response relationships accounting for correlated data structure and heterogeneous error variances. To illustrate, we modeled data from a randomized complete block design study to evaluate the standardized ileal digestible (SID) Trp:Lys ratio dose-response on G:F of nursery pigs. A base linear mixed model was fitted to explore the functional form of G:F relative to Trp:Lys ratios and assess model assumptions. Next, we fitted 3 competing dose-response mixed models to G:F, namely a quadratic polynomial (QP) model, a broken-line linear (BLL) ascending model, and a broken-line quadratic (BLQ) ascending model, all of which included heteroskedastic specifications, as dictated by the base model. The GLIMMIX procedure of SAS (version 9.4) was used to fit the base and QP models and the NLMIXED procedure was used to fit the BLL and BLQ models. We further illustrated the use of a grid search of initial parameter values to facilitate convergence and parameter estimation in nonlinear mixed models. Fit between competing dose-response models was compared using a maximum likelihood-based Bayesian information criterion (BIC). The QP, BLL, and BLQ models fitted on G:F of nursery pigs yielded BIC values of 353.7, 343.4, and 345.2, respectively, thus indicating a better fit of the BLL model. The BLL breakpoint estimate of the SID Trp:Lys ratio was 16.5% (95% confidence interval [16.1, 17.0]). Problems with

A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer.

Science.gov (United States)

Wang, F; Yeung, K L; Chan, W C; Kwok, C C H; Leung, S L; Wu, C; Chan, E Y Y; Yu, I T S; Yang, X R; Tse, L A

2013-11-01

This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach. We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies. Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; Pheterogeneity night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21; Pheterogeneity = 0.06) increase in breast cancer risk. This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.

Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease.

Science.gov (United States)

Qi, Hui; Li, Shixue

2014-04-01

A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption. A comprehensive search was carried out to identify eligible studies. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline. A total of 13 articles involving 901 764 participants for coffee, eight articles involving 344 895 participants for tea and seven articles involving 492 724 participants for caffeine were included. A non-linear relationship was found between coffee consumption and PD risk overall, and the strength of protection reached the maximum at approximately 3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65-0.81). A linear relationship was found between tea and caffeine consumption, and PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for every two cups/day and 200 mg/day increments, respectively. The association of coffee and tea consumption with PD risk was stronger for men than that for women, and the association of caffeine consumption with PD risk was stronger for ever users of hormones than that for never users of hormones among postmenopausal women. The aforementioned associations were weaker for USA relative to Europe or Asia. A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings. © 2013 Japan Geriatrics Society.

Adaptive regression for modeling nonlinear relationships

CERN Document Server

Knafl, George J

2016-01-01

This book presents methods for investigating whether relationships are linear or nonlinear and for adaptively fitting appropriate models when they are nonlinear. Data analysts will learn how to incorporate nonlinearity in one or more predictor variables into regression models for different types of outcome variables. Such nonlinear dependence is often not considered in applied research, yet nonlinear relationships are common and so need to be addressed. A standard linear analysis can produce misleading conclusions, while a nonlinear analysis can provide novel insights into data, not otherwise possible. A variety of examples of the benefits of modeling nonlinear relationships are presented throughout the book. Methods are covered using what are called fractional polynomials based on real-valued power transformations of primary predictor variables combined with model selection based on likelihood cross-validation. The book covers how to formulate and conduct such adaptive fractional polynomial modeling in the s...

Dose-response relationship for breast cancer induction at radiotherapy dose

Directory of Open Access Journals (Sweden)

Gruber Günther

2011-06-01

Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

Epidemiological methods for assessing dose-response and dose-effect relationships

DEFF Research Database (Denmark)

Kjellström, Tord; Grandjean, Philippe

2007-01-01

Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity General Considerations of Dose-Effect and Dose-Response Relationships Interactions in Metal Toxicology Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships Essential Metals: Assessing Risks from Deficiency......Description Handbook of the Toxicology of Metals is the standard reference work for physicians, toxicologists and engineers in the field of environmental and occupational health. This new edition is a comprehensive review of the effects on biological systems from metallic elements...... access to a broad range of basic toxicological data and also gives a general introduction to the toxicology of metallic compounds. Audience Toxicologists, physicians, and engineers in the fields of environmental and occupational health as well as libraries in these disciplines. Will also be a useful...

Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies.

Science.gov (United States)

Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B

2014-02-11

Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified (P for heterogeneity=0.09, P for trend coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87-1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80-0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84-0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease (P for heterogeneity=0.001, P for trend 0.05) risks. A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.

Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies

Science.gov (United States)

Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B

2013-01-01

Background Considerable controversy exists regarding the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. Methods and Results Pubmed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1,279,804 participants and 36,352 CVD cases. A non-linear relationship of coffee consumption with CVD risk was identified (P for heterogeneity = 0.09, P for trend coffee consumption (median: 0 cups/d), the relative risk of CVD was 0.95 (95% CI, 0.87 to 1.03) for the highest (median: 5 cups/d) category, 0.85 (0.80 to 0.90) for the second highest (median: 3.5 cups/d), and 0.89 (0.84 to 0.94) for the third highest category (median: 1.5 cups/d). Looking at separate outcomes, coffee consumption was non-linearly associated with both CHD (P for heterogeneity = 0.001, P for trend 0.05). Conclusions A non-linear association between coffee consumption with CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups/d, and heavy coffee consumption was not associated with elevated CVD risk. PMID:24201300

Dose-response relationship between cigarette smoking and site-specific cancer risk: protocol for a systematic review with an original design combining umbrella and traditional reviews.

Science.gov (United States)

Lugo, Alessandra; Bosetti, Cristina; Peveri, Giulia; Rota, Matteo; Bagnardi, Vincenzo; Gallus, Silvano

2017-11-01

Only a limited number of meta-analyses providing risk curve functions of dose-response relationships between various smoking-related variables and cancer-specific risk are available. To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose-response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose-response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose-response relationship framework. Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden

Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies.

Science.gov (United States)

Yao, Baodong; Yan, Yujie; Ye, Xianwu; Fang, Hong; Xu, Huilin; Liu, Yinan; Li, Sheran; Zhao, Yanping

2014-12-01

Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

Dose-stochastic radiobiological effect relationship in model of two reactions and estimation of radiation risk

International Nuclear Information System (INIS)

Komochkov, M.M.

1997-01-01

The model of dose-stochastic effect relationship for biological systems capable of self-defence under danger factor effect is developed. A defence system is realized in two forms of organism reaction, which determine innate μ n and adaptive μ a radiosensitivities. The significances of μ n are determined by host (inner) factors; and the significances of μ a , by external factors. The possibilities of adaptive reaction are determined by the coefficient of capabilities of the defence system. The formulas of the dose-effect relationship are the solutions of differential equations of assumed process in the defence system of organism. The model and formulas have been checked both at cell and at human levels. Based on the model and personal monitoring data, the estimation of radiation risk at the Joint Institute for Nuclear Research is done

LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION

International Nuclear Information System (INIS)

Flynn, James

2002-01-01

The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low-dose exposures. Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low-dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

Dose evaluation and risk estimation for secondary cancer in contralateral breast and a study of correlation between thorax shape and dose to organs at risk following tangentially breast irradiation during deep inspiration breath-hold and free breathing

International Nuclear Information System (INIS)

Johansen, Safora; Vikstroem, Johan; Blihovde Hjelstuen, Mari Helene; Mjaaland, Ingvil; Dybvik, Kjell Ivar; Olsen, Dag Rune

2011-01-01

Purpose: To assess the impact of using breathing adapted radiotherapy on contralateral breast (CB) dose, to relate the thorax shape with the dose to the organs at risk (OARs) and to predict the risk for induced malignancies in CB using linear and non-linear models, following tangential irradiation of breast. Material and methods. Sixteen patients with stage I-II breast cancer treatment planned with tangential fields using deep inspiration breath hold (DIBH) and free breathing (FB) techniques were included in this analysis. The dose results mainly based on DVH analysis were compared. Four parameters were defined to describe thoracic shape. Excess relative risk (ERR) for cancer induction in CB, employing linear and non-linear models was calculated. Results. Average CB volumes exposed to a dose of 1 Gy is 1.3 times higher in DIBH plans than in FB plans. No significant difference in average V3Gy and V5Gy for DIBH and FB plans is observed. The average mean CB dose for DIBH and FB plans is 0.33 and 0.28 Gy, respectively. No correlation between thorax shape parameters and mean OARs dose is observed. The estimated average mean ERR with linear model is lower in FB plans (0.12) than for the DIBH plans (0.14). The estimated ERR with non-linear model is 0.14 for DIBH plans and 0.15 for FB plans. Conclusion. No significant difference in CB dose between DIBH and FB plans is observed. The four thorax shape parameters defined in this study can not be related to the dose at OARs using DIBH and FB radiation techniques. The ERR estimates for secondary CB cancer are nearly the same for FB and DIBH planning when using a linear and non-linear risk prediction models

Plutonium dose-effect relationship

International Nuclear Information System (INIS)

Matsuoka, Osamu

1976-01-01

Dose in internal exposure to Pu was investigated, and dose-effect relationship was discussed. Dose-effect relationship in internal exposure was investigated by means of two methods, which were relationship between dose and its effect (relationship between μ Ci/Kg and its effect), and exposure dose and its effects (rad-effect), and merits and demerits of two methods were mentioned. Problems in a indication method such as mean dose were discussed with respect to the dose in skeleton, the liver and the lung. Pu-induced osteosarcoma in mice rats, and beagles was described, and differences in its induction between animals were discussed. Pulmonary neoplasma induced by 239 PuO 2 inhalation in beagles was reported, and description was made as to differences in induction of lung cancer between animals when Pu was inhaled and was taken into the lung. A theoretical and experimental study of a extrapolation of the results of the animal experiment using Pu to human cases is necessary. (Serizawa, K.)

Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

International Nuclear Information System (INIS)

Ogata, Hiromitsu; Magae, Junji

2008-01-01

Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

Low-Dose Risk, Decisions, and Risk Communication

International Nuclear Information System (INIS)

Flynn, James; Slovic, Paul

2001-01-01

To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email and internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

Dose - response relationship between noise exposure and the risk of occupational injury

Directory of Open Access Journals (Sweden)

Jin-Ha Yoon

2015-01-01

Full Text Available Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers′ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively. Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals derived from a logistic regression model were 1.68 (1.27-2.24 and 3.42 (2.26-5.17 at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry

International Nuclear Information System (INIS)

Metz-Flamant, Camille

2011-01-01

The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation

A method to adjust radiation dose-response relationships for clinical risk factors

DEFF Research Database (Denmark)

Appelt, Ane Lindegaard; Vogelius, Ivan R

2012-01-01

Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

Linear-No-Threshold Default Assumptions for Noncancer and Nongenotoxic Cancer Risks: A Mathematical and Biological Critique.

Science.gov (United States)

Bogen, Kenneth T

2016-03-01

To improve U.S. Environmental Protection Agency (EPA) dose-response (DR) assessments for noncarcinogens and for nonlinear mode of action (MOA) carcinogens, the 2009 NRC Science and Decisions Panel recommended that the adjustment-factor approach traditionally applied to these endpoints should be replaced by a new default assumption that both endpoints have linear-no-threshold (LNT) population-wide DR relationships. The panel claimed this new approach is warranted because population DR is LNT when any new dose adds to a background dose that explains background levels of risk, and/or when there is substantial interindividual heterogeneity in susceptibility in the exposed human population. Mathematically, however, the first claim is either false or effectively meaningless and the second claim is false. Any dose-and population-response relationship that is statistically consistent with an LNT relationship may instead be an additive mixture of just two quasi-threshold DR relationships, which jointly exhibit low-dose S-shaped, quasi-threshold nonlinearity just below the lower end of the observed "linear" dose range. In this case, LNT extrapolation would necessarily overestimate increased risk by increasingly large relative magnitudes at diminishing values of above-background dose. The fact that chemically-induced apoptotic cell death occurs by unambiguously nonlinear, quasi-threshold DR mechanisms is apparent from recent data concerning this quintessential toxicity endpoint. The 2009 NRC Science and Decisions Panel claims and recommendations that default LNT assumptions be applied to DR assessment for noncarcinogens and nonlinear MOA carcinogens are therefore not justified either mathematically or biologically. © 2015 The Author. Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

Radiation-Induced Rib Fractures After Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors and Dose-Volume Relationship

Energy Technology Data Exchange (ETDEWEB)

Asai, Kaori [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp [Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Nakamura, Katsumasa; Sasaki, Tomonari; Ohga, Saiji; Nonoshita, Takeshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yoshitake, Tadamasa [Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Ohnishi, Kayoko [Department of Radiology, National Center for Global Health and Medicine, Tokyo (Japan); Terashima, Kotaro; Matsumoto, Keiji [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Hirata, Hideki [Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan)

2012-11-01

Purpose: The purpose of this study was to clarify the incidence, the clinical risk factors, and the dose-volume relationship of radiation-induced rib fracture (RIRF) after hypofractionated stereotactic body radiation therapy (SBRT). Methods and Materials: One hundred sixteen patients treated with SBRT for primary or metastatic lung cancer at our institution, with at least 6 months of follow-up and no previous overlapping radiation exposure, were included in this study. To determine the clinical risk factors associated with RIRF, correlations between the incidence of RIRF and the variables, including age, sex, diagnosis, gross tumor volume diameter, rib-tumor distance, and use of steroid administration, were analyzed. Dose-volume histogram analysis was also conducted. Regarding the maximum dose, V10, V20, V30, and V40 of the rib, and the incidences of RIRF were compared between the two groups divided by the cutoff value determined by the receiver operating characteristic curves. Results: One hundred sixteen patients and 374 ribs met the inclusion criteria. Among the 116 patients, 28 patients (46 ribs) experienced RIRF. The estimated incidence of rib fracture was 37.7% at 3 years. Limited distance from the rib to the tumor (<2.0 cm) was the only significant risk factor for RIRF (p = 0.0001). Among the dosimetric parameters used for receiver operating characteristic analysis, the maximum dose showed the highest area under the curve. The 3-year estimated risk of RIRF and the determined cutoff value were 45.8% vs. 1.4% (maximum dose, {>=}42.4 Gy or less), 51.6% vs. 2.0% (V40, {>=}0.29 cm{sup 3} or less), 45.8% vs. 2.2% (V30, {>=}1.35 cm{sup 3} or less), 42.0% vs. 8.5% (V20, {>=}3.62 cm{sup 3} or less), or 25.9% vs. 10.5% (V10, {>=}5.03 cm{sup 3} or less). Conclusions: The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF.

The Changing Nonlinear Relationship between Income and Terrorism

Science.gov (United States)

Enders, Walter; Hoover, Gary A.

2014-01-01

This article reinvestigates the relationship between real per capita gross domestic product (GDP) and terrorism. We devise a terrorism Lorenz curve to show that domestic and transnational terrorist attacks are each more concentrated in middle-income countries, thereby suggesting a nonlinear income–terrorism relationship. Moreover, this point of concentration shifted to lower income countries after the rising influence of the religious fundamentalist and nationalist/separatist terrorists in the early 1990s. For transnational terrorist attacks, this shift characterized not only the attack venue but also the perpetrators’ nationality. The article then uses nonlinear smooth transition regressions to establish the relationship between real per capita GDP and terrorism for eight alternative terrorism samples, accounting for venue, perpetrators’ nationality, terrorism type, and the period. Our nonlinear estimates are shown to be favored over estimates using linear or quadratic income determinants of terrorism. These nonlinear estimates are robust to additional controls. PMID:28579636

Teratogenic radiation effects: Phenomena, dose-response relationships and risk levels

International Nuclear Information System (INIS)

Konermann, G.

1991-01-01

The report in hand informs about a study performed within the framework of the research project 'Animal experiments with albino mice for establishing a model for the detection and assessment of radiation-induced, developmental risks in man due to low-dose irradiation'. The subjects investigated in this study are: (1) Dose-response relationships for postnatal developmental disturbances of the brain as a result of prenatal X-ray treatment. (2) Biokinetics, distribution patterns and effects of inorganically and organically bonded radioiodine (I-125) during the phase of development of the brain. For investigation of the first-mentioned subject, computerized microphotograph analysis was applied for detecting and assessing disturbances of the alignment of axons, as well as deviations from normal cross-sectional data of the Cortex layer, and cerebral commissures as final locations of neurogenetic damage. With all parameters studied, the slope of the relevant curves was found to decrease as a function of age of the fetus at the time of exposure. In addition, time factor effects were investigated. For the parameter cross-sectional area of the Cortex, a clear decrease of effect was found, but for all other parameters, reactions were ambiguous. The study into the second subject was done with cell cultures, showing that the I-125 bonded to the cell nucleus has a much stronger radiotoxic effect than I-125 bonded to the cytoplasma. This difference in effect was studied in mice after incorporation of equal doses administered by way of (I-125)-sodium iodide or (I-125)-iododesoxyuridine. Long-term effects on Cortex cross-sectional areas, cerebral commissures or the texture of axons were quantified by microphotograph analysis. Acute cell death and initial disturbances of the neuronal cell growth were evident after incorporation of (I-125)-IdUR, but not detectable after administration of (I-125)-NaI. (orig./MG) [de

Knowledge of medical imaging radiation dose and risk among doctors

International Nuclear Information System (INIS)

Brown, Nicholas; Jones, Lee

2013-01-01

The growth of computed tomography (CT) and nuclear medicine (NM) scans has revolutionised healthcare but also greatly increased population radiation doses. Overuse of diagnostic radiation is becoming a feature of medical practice, leading to possible unnecessary radiation exposures and lifetime-risks of developing cancer. Doctors across all medical specialties and experience levels were surveyed to determine their knowledge of radiation doses and potential risks associated with some diagnostic imaging. A survey relating to knowledge and understanding of medical imaging radiation was distributed to doctors at 14 major Queensland public hospitals, as well as fellows and trainees in radiology, emergency medicine and general practice. From 608 valid responses, only 17.3% correctly estimated the radiation dose from CT scans and almost 1 in 10 incorrectly believed that CT radiation is not associated with any increased lifetime risk of developing cancer. There is a strong inverse relationship between a clinician's experience and their knowledge of CT radiation dose and risks, even among radiologists. More than a third (35.7%) of doctors incorrectly believed that typical NM imaging either does not use ionising radiation or emits doses equal to or less than a standard chest radiograph. Knowledge of CT and NM radiation doses is poor across all specialties, and there is a significant inverse relationship between experience and awareness of CT dose and risk. Despite having a poor understanding of these concepts, most doctors claim to consider them prior to requesting scans and when discussing potential risks with patients.

Effect of heterogeneity of human population in cell radiosensitivity on the extrapolation of dose-response relationships to low doses

International Nuclear Information System (INIS)

Filyushkin, I.V.; Bragin, Yu.N.; Khandogina, E.K.

1989-01-01

Presented are the results of an investigation of the dose-response relationship for the yield of chromosome aberrations in peripheral blood lymphocytes of persons with some hereditary diseases which represent the high risk group with respect to the increased incidence of malignant tumors and decreased life span. Despite substantially different absolute radiosensitivities of chromosomes, the variations of the alpha/beta ratio determining the extrapolation of experimental dose-response relationships to low doses did not prove to be too high, the mean deviation from the control being 15%. This points to the possible practical use of the dose-response relationships averaged over the human population as a whole

Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

OpenAIRE

Lagarde, Fabien; Beausoleil, Claire; Belcher, Scott M; Belzunces, Luc P; Emond, Claude; Guerbet, Michel; Rousselle, Christophe

2015-01-01

International audience; Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that repor...

Dose — response relationship between noise exposure and the risk of occupational injury

Science.gov (United States)

Yoon, Jin-Ha; Hong, Jeong-Suk; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

2015-01-01

Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers’ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively). Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and 3.42 (2.26-5.17) at 80-89 dB and ≥90 dB versus occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury. PMID:25599757

Non-Linear Dose-Response Relationships in Biology, Toxicology and Medicine - An International Conference

Energy Technology Data Exchange (ETDEWEB)

Calabrese, Edward J.; Kostecki, Paul T.

2002-05-28

Conference abstract book contains seven sections: Plenary-4 abstracts; Chemical-9 abstracts; Radiation-7 abstracts; Ultra Low Doses and Medicine-6 abstracts; Biomedical-11 abstracts; Risk Assessment-5 abstracts and Poster Sessions-25 abstracts. Each abstract was provided by the author/presenter participating in the conference.

Defining a dose-response relationship for prostate external beam radiotherapy

International Nuclear Information System (INIS)

Trada, Yuvnik; Plank, Ash; Martin, Jarad

2013-01-01

We aimed to quantify a relationship between radiotherapy dose and freedom from biochemical failure (FFBF) in low- and intermediate-risk prostate cancer. To reduce confounding we used data with a standardised end–point, mature follow-up, low competing risk of metastatic failure, conventional fractionation and separate reporting for outcomes with hormonal therapy (HT). A systematic review of the literature was carried out. Studies that reported the use of radiotherapy alone in 1.8–2Gy fractions in low- and intermediate-risk prostate cancer were included. The primary end–point was Phoenix definition 5-year FFBF. A logistic regression was used to quantify the dose–response relationship. Data from eight studies with 3037 patients met the inclusion criteria. The data from 810 low-risk patients and 2245 intermediate-risk patients were analysed. A strong association between radiotherapy dose and FFBF was found in low- and intermediate-risk patients managed with radiotherapy alone. In low-risk patients not treated with HT the dose required to achieve 50% biochemical tumour control (TCD 50 ) is 52.0 Gy and the slope of the dose–response curve at TCD 50 (γ 50 ) is 2.1%/Gy. At 78Gy this represented a FFBF of 90.3%. In intermediate-risk patients not treated with HT the TCD 50 is 64.7Gy and γ 50 is 3.2%/Gy. At 78 Gy this translated into a FFBF of 84.3%. HT had a small effect for low-risk patients and an inconsistent effect for intermediate-risk men. A strong association was found between radiation dose and biochemical outcome in both low- and intermediate-risk patients. Standardised reporting of results from future studies will make future analyses more robust.

The biological bases of the dose-effect relationship

International Nuclear Information System (INIS)

Lafuma, J.

2001-01-01

In radiation protection, the recent data in epidemiology, in animal experimentation and on the base researches are no more compatible with a linear dose-effect relationship without threshold and do not account for the radiological risks at low doses. The cancers should be accelerated by radiations as any pathology linked to the ageing and for which threshold exit. Relative to the genetic risk it is known today that the natural exposure that lasts for several generations has not lead excess of hereditary illness as it was to be feared in 1959 for several countries. Considering that for populations the exposure levels induced by human activities have already been, under these ones of average natural exposures the genetic risk can be negligible and it is the somatic risk alone, with its thresholds that has to be into account. (N.C.)

Implications of effects ''adaptive response'', ''low-dose hypersensitivity'' und ''bystander effect'' for cancer risk at low doses and low dose rates

International Nuclear Information System (INIS)

Jacob, P

2006-01-01

A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer mortality data. All models examined resulted in the predominant number of Mayak lung cancer deaths being ascribed to smoking. The interaction between smoking and plutonium exposures was found to be the second largest effect. The TSCE model resulted in lower estimates for the lung cancer excess relative risk per unit plutonium dose than the empirical risk model, but this difference was not found to be statistically significant. The excess relative risk dose responses were linear in the empirical model and

Radiation dose-response relationship of micronucleus occurrence in pollen mother cells of tradescantia

International Nuclear Information System (INIS)

Kim, Jin Kyu; Kim, Yeon Ku; Song, Hi Sup

1999-01-01

This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronucleus showed a good dose-response relationship in the range of dose 0∼50 cGy. On the basis of the relationship, a dose of 1 cGy resulted in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiation and can be modified for biological risk assessment of toxicants, and to safety test of water or soil integrity

Three-dimensional dose-response models of risk for radiation injury carcinogenesis

International Nuclear Information System (INIS)

Raabe, O.G.

1988-01-01

The use of computer graphics in conjunction with three-dimensional models of dose-response relationships for chronic exposure to ionizing radiation dramaticly clarifies the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. As an example, the functionally injurious and carcinogenic responses after systemic uptake of Ra-226 by beagles, mice and people with consequent alpha particle irradiation of the bone are represented by three-dimensional dose-rate/time/response surfaces that demonstrate the contributions with the passage of time of the competing deleterious responses. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each effect. Radiation bone injury predominates at high dose rates and bone cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for bone cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to planning and evaluating epidemiological analyses and experimental studies

Influence of dose and its distribution in time on dose-response relationships for low-LET radiation

International Nuclear Information System (INIS)

Anon.

1980-01-01

This book examines the influence of dose rate and magnitude on the genetic and carcinogenic effects of radiation exposure in animals and man. It systematically examines a broad range of biological effects in simple systems, plants, laboratory animals, and man with special attention given to the effects of prenatal irradiation, changes in life span, and tumorigenesis. An enormous volume of data is provided about human tumorigenesis and the data and shortcomings are summarized. There is an extended general discussion of the consideration in quantitative dose and dose rate relationships and of the limitations of the data and analyses which have led to a linear interpolation of risk at low doses and dose rates. An argument is made for dose rate dependence in tumorigenesis as being consistent with all other radiation effects and for the applicability of Dose Rate Effectiveness Factors (DREF) in providing a more realistic assessment of the risk of radiation carcinogenesis. The report is documented with 24 pages of references. There are numerous graphs and tables, all clear and to the point. This book is a superb review and summary of the data on radiation risks

Knowledge of medical imaging radiation dose and risk among doctors.

Science.gov (United States)

Brown, Nicholas; Jones, Lee

2013-02-01

The growth of computed tomography (CT) and nuclear medicine (NM) scans has revolutionised healthcare but also greatly increased population radiation doses. Overuse of diagnostic radiation is becoming a feature of medical practice, leading to possible unnecessary radiation exposures and lifetime-risks of developing cancer. Doctors across all medical specialties and experience levels were surveyed to determine their knowledge of radiation doses and potential risks associated with some diagnostic imaging. A survey relating to knowledge and understanding of medical imaging radiation was distributed to doctors at 14 major Queensland public hospitals, as well as fellows and trainees in radiology, emergency medicine and general practice. From 608 valid responses, only 17.3% correctly estimated the radiation dose from CT scans and almost 1 in 10 incorrectly believed that CT radiation is not associated with any increased lifetime risk of developing cancer. There is a strong inverse relationship between a clinician's experience and their knowledge of CT radiation dose and risks, even among radiologists. More than a third (35.7%) of doctors incorrectly believed that typical NM imaging either does not use ionising radiation or emits doses equal to or less than a standard chest radiograph. Knowledge of CT and NM radiation doses is poor across all specialties, and there is a significant inverse relationship between experience and awareness of CT dose and risk. Despite having a poor understanding of these concepts, most doctors claim to consider them prior to requesting scans and when discussing potential risks with patients. © 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.

Body mass index had different effects on premenopausal and postmenopausal breast cancer risks: a dose-response meta-analysis with 3,318,796 subjects from 31 cohort studies.

Science.gov (United States)

Chen, Yanzi; Liu, Li; Zhou, Quan; Imam, Mustapha Umar; Cai, Jialin; Wang, Yaxuan; Qi, Minjie; Sun, Panpan; Ping, Zhiguang; Fu, Xiaoli

2017-12-08

There is sufficient evidence supporting a relationship between increased body mass index (BMI) and an increased risk for breast cancer among postmenopausal women. However, most studies have found a decreased risk for premenopausal breast cancer. This study was conducted to find out the different effects of BMI on the risk of breast cancer among premenopausal and postmenopausal women, and explore the potential factors that influence the associations. A dose-response meta-analysis with 3,318,796 participants from 31 articles was conducted. Cohort studies that included BMI and corresponding breast cancer risk were selected through various databases including PubMed, Medline, Web of Science, the China National Knowledge Infrastructure (CNKI) and Chinese Scientific Journals (VIP). Random effects models were used for analyzing the data. The summary relative risks (RRs) were 1.33 (95%CI: 1.20-1.48) and 0.94(95%CI: 0.80-1.11) among postmenopausal and premenopausal women, respectively. The dose-response meta-analysis indicated a positive non-linear association between BMI and breast cancer risk among postmenopausal women, and compared to the mean level of the normal BMI category (21.5 kg/m 2 ) the RR in total postmenopausal women were1.03 (95% CI: 1.02-1.05) per 1 kg/m 2 increment. However, no statistically significant association among total premenopausal women was detected. In subgroup analysis among European premenopausal women, the summary RR was 0.79(95%CI: 0.70-0.88). The non-linear relationship showed a negative non-linear association between BMI and breast cancer risk among European premenopausal women. When compared to the mean level of the normal BMI category, the RRs were 0.98 (95%CI: 0.96-1.00) per 1 kg/m 2 increment, respectively. In line with previous studies BMI had different effects on pre-menopausal and postmenopausal breast cancer risk. However, contrary to previous studies, a high BMI was not associated with decreased risk in total pre-menopausal women

Nonlinear association between betel quid chewing and oral cancer: Implications for prevention.

Science.gov (United States)

Madathil, Sreenath Arekunnath; Rousseau, Marie-Claude; Wynant, Willy; Schlecht, Nicolas F; Netuveli, Gopalakrishnan; Franco, Eduardo L; Nicolau, Belinda

2016-09-01

Betel quid chewing is a major oral cancer risk factor and the human papillomaviruses (HPV) may play an aetiological role in these cancers. However, little is known about the shape of the dose-response relationship between the betel quid chewing habit and oral cancer risk in populations without HPV. We estimate the shape of this dose-response relationship, and discuss implications for prevention. Cases with oral squamous cell carcinoma (350) and non-cancer controls (371) were recruited from two major teaching hospitals in South India. Information on socio-demographic and behavioral factors was collected using a questionnaire and the life grid technique. The effect of daily amount of use and duration of the habit were estimated jointly as risk associated with cumulative exposure (chew-years). The shape of the dose-response curve was estimated using restricted cubic spline transformation of chew-years in a conditional logistic regression model. Risk estimates for low dose combinations of daily amount and duration of the habit were computed from flexible regression. Most (72%) oral cancer cases were betel quid chewers in contrast to only 18% of controls. A nonlinear dose-response relationship was observed; the risk increased steeply at low doses and plateaued at high exposures to betel quid (>425 chew-years). A threefold increase in risk (OR=3.92, 95%CI: 1.87-8.21) was observed for the lowest dose; equivalent to the use of one quid per day for one year. Our findings may be used to counsel people to refrain from even low betel quid chewing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry; Effets sanitaires des faibles doses a faibles debits de dose: modelisation de la relation dose-reponse dans une cohorte de travailleurs du nucleaire

Energy Technology Data Exchange (ETDEWEB)

Metz-Flamant, Camille

2011-09-19

The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation

Dose-Response—A Challenge for Allelopathy?

OpenAIRE

Belz, Regina G.; Hurle, Karl; Duke, Stephen O.

2005-01-01

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of no...

The biological bases of the dose-effect relationship; Les bases biologiques de la relation dose-effet

Energy Technology Data Exchange (ETDEWEB)

Lafuma, J

2001-06-01

In radiation protection, the recent data in epidemiology, in animal experimentation and on the base researches are no more compatible with a linear dose-effect relationship without threshold and do not account for the radiological risks at low doses. The cancers should be accelerated by radiations as any pathology linked to the ageing and for which threshold exit. Relative to the genetic risk it is known today that the natural exposure that lasts for several generations has not lead excess of hereditary illness as it was to be feared in 1959 for several countries. Considering that for populations the exposure levels induced by human activities have already been, under these ones of average natural exposures the genetic risk can be negligible and it is the somatic risk alone, with its thresholds that has to be into account. (N.C.)

Analyzing systemic risk using non-linear marginal expected shortfall and its minimum spanning tree

Science.gov (United States)

Song, Jae Wook; Ko, Bonggyun; Chang, Woojin

2018-02-01

The aim of this paper is to propose a new theoretical framework for analyzing the systemic risk using the marginal expected shortfall (MES) and its correlation-based minimum spanning tree (MST). At first, we develop two parametric models of MES with their closed-form solutions based on the Capital Asset Pricing Model. Our models are derived from the non-symmetric quadratic form, which allows them to consolidate the non-linear relationship between the stock and market returns. Secondly, we discover the evidences related to the utility of our models and the possible association in between the non-linear relationship and the emergence of severe systemic risk by considering the US financial system as a benchmark. In this context, the evolution of MES also can be regarded as a reasonable proxy of systemic risk. Lastly, we analyze the structural properties of the systemic risk using the MST based on the computed series of MES. The topology of MST conveys the presence of sectoral clustering and strong co-movements of systemic risk leaded by few hubs during the crisis. Specifically, we discover that the Depositories are the majority sector leading the connections during the Non-Crisis period, whereas the Broker-Dealers are majority during the Crisis period.

Regional variability among nonlinear chlorophyll-phosphorus relationships in lakes

Science.gov (United States)

Filstrup, Christopher T.; Wagner, Tyler; Soranno, Patricia A.; Stanley, Emily H.; Stow, Craig A.; Webster, Katherine E.; Downing, John A.

2014-01-01

The relationship between chlorophyll a (Chl a) and total phosphorus (TP) is a fundamental relationship in lakes that reflects multiple aspects of ecosystem function and is also used in the regulation and management of inland waters. The exact form of this relationship has substantial implications on its meaning and its use. We assembled a spatially extensive data set to examine whether nonlinear models are a better fit for Chl a—TP relationships than traditional log-linear models, whether there were regional differences in the form of the relationships, and, if so, which regional factors were related to these differences. We analyzed a data set from 2105 temperate lakes across 35 ecoregions by fitting and comparing two different nonlinear models and one log-linear model. The two nonlinear models fit the data better than the log-linear model. In addition, the parameters for the best-fitting model varied among regions: the maximum and lower Chl aasymptotes were positively and negatively related to percent regional pasture land use, respectively, and the rate at which chlorophyll increased with TP was negatively related to percent regional wetland cover. Lakes in regions with more pasture fields had higher maximum chlorophyll concentrations at high TP concentrations but lower minimum chlorophyll concentrations at low TP concentrations. Lakes in regions with less wetland cover showed a steeper Chl a—TP relationship than wetland-rich regions. Interpretation of Chl a—TP relationships depends on regional differences, and theory and management based on a monolithic relationship may be inaccurate.

The crooked shall be made straight: dose response relationships for carcinogenesis

International Nuclear Information System (INIS)

Hall, E.J.

2003-01-01

Estimates of radiation-induced malignancies come principally from the A-bomb survivors and from medically exposed individuals, including second cancers in radiotherapy patients. The A-bomb survivors show an excess incidence of carcinomas which is linear with dose from about 10 cGy to 2.5 Gy. Above and below this dose range, there is considerable uncertainty concerning the shape of the dose response relationship. These two dose ranges will be discussed separately. Low dose extrapolations ICRP and NCRP suggest that cancer risks at doses lower than those at which direct epidemiological observations are possible should be obtained by a linear extrapolation from higher doses. This is labeled a 'prudent and conservative' assumption but is a subject of considerable controversy. Two factors, the existence of radiosensitive subgroups in the human population (such as AT heterozygotes), and the demonstration of a Bystander effect both exaggerate the consequences of small doses of radiation and imply that a linear extrapolation from high doses would underestimate low dose risks. High dose extrapolations In the context of radiotherapy, some normal tissues receive 70 Gy, while a larger volume receives a lower dose, but still far higher than the range for which data are available from the A-bomb survivors. The question is, what is the dose response for carcinogenesis in the range 10 to 70 Gy? At one extreme, it might be expected that the risk of inducing cancer would fall off rapidly at higher does due to cell killing. The other extreme possibility is that the risk of solid tumors levels off by about 10 Gy, but does not decline thereafter. For a few cancers, data are available from 2 Gy in A-bomb survivors to 70 Gy in radiotherapy patients, and it appears that the relative risk does not vary with dose. This implies that the volume of tissue irradiated is more important than the maximum dose. This result has far reaching implications for new technologies such as IMRT, which

Dose dependence on stochastic radiobiological effect in radiation risk estimation

International Nuclear Information System (INIS)

Komochkov, M.M.

1999-01-01

The analysis of the results in dose -- effect relationship observation has been carried out on the cell and organism levels, with the aim to obtain more precise data on the risk coefficients at low doses. The results are represented by two contrasting groups of dose dependence on effect: a downwards concave and a J-shaped curve. Both types of dependence are described by the equation solutions of an assumed unified protective mechanism, which comprises two components: constitutive and adaptive or inducible ones. The latest data analysis of the downwards concave dependence curves shows a considerable underestimation of radiation risk in all types of cancer, except leukemia, for a number of critical groups in a population, at low doses comparing to the ICRP recommendations. With the dose increase, the decrease of the effect value per dose unit is observed. It may be possibly related to the switching of the activity of the adaptive protective mechanism, with some threshold dose values being exceeded

A biological basis for the linear non-threshold dose-response relationship for low-level carcinogen exposure

International Nuclear Information System (INIS)

Albert, R.E.

1981-01-01

This chapter examines low-level dose-response relationships in terms of the two-stage mouse tumorigenesis model. Analyzes the feasibility of the linear non-threshold dose-response model which was first adopted for use in the assessment of cancer risks from ionizing radiation and more recently from chemical carcinogens. Finds that both the interaction of B(a)P with epidermal DNA of the mouse skin and the dose-response relationship for the initiation stage of mouse skin tumorigenesis showed a linear non-threshold dose-response relationship. Concludes that low level exposure to environmental carcinogens has a linear non-threshold dose-response relationship with the carcinogen acting as an initiator and the promoting action being supplied by the factors that are responsible for the background cancer rate in the target tissue

Dose-response relationship with radiotherapy: an evidence?

International Nuclear Information System (INIS)

Chauvet, B.; Rauglaudre, G. de; Mineur, L.; Alfonsi, M.; Reboul, F.

2003-01-01

The dose-response relationship is a fundamental basis of radiobiology. Despite many clinical data, difficulties remain to demonstrate a relation between dose and local control: relative role of treatment associated with radiation therapy (surgery, chemotherapy, hormonal therapy), tumor heterogeneity, few prospective randomized studies, uncertainty of local control assessment. Three different situations are discussed: tumors with high local control probabilities for which dose effect is demonstrated by randomized studies (breast cancer) or sound retrospective data (soft tissues sarcomas), tumors with intermediate local control probabilities for which dose effect seems to be important according to retrospective studies and ongoing or published phase III trials (prostate cancer), tumors with low local control probabilities for which dose effect appears to be modest beyond standard doses, and inferior to the benefit of concurrent chemotherapy (lung and oesophageal cancer). For head and neck tumors, the dose-response relationship has been explored through hyperfractionation and accelerated radiation therapy and a dose effect has been demonstrated but must be compared to the benefit of concurrent chemotherapy. Last but not least, the development of conformal radiotherapy allow the exploration of the dose response relationship for tumors such as hepatocellular carcinomas traditionally excluded from the field of conventional radiation therapy. In conclusion, the dose-response relationship remains a sound basis of radiation therapy for many tumors and is a parameter to take into account for further randomized studies. (author)

Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies.

Science.gov (United States)

Han, Hedong; Fang, Xin; Wei, Xin; Liu, Yuzhou; Jin, Zhicao; Chen, Qi; Fan, Zhongjie; Aaseth, Jan; Hiyoshi, Ayako; He, Jia; Cao, Yang

2017-05-05

The findings of prospective cohort studies are inconsistent regarding the association between dietary magnesium intake and serum magnesium concentration and the risk of hypertension. We aimed to review the evidence from prospective cohort studies and perform a dose-response meta-analysis to investigate the relationship between dietary magnesium intake and serum magnesium concentrations and the risk of hypertension. We searched systematically PubMed, EMBASE and the Cochrane Library databases from October 1951 through June 2016. Prospective cohort studies reporting effect estimates with 95% confidence intervals (CIs) for hypertension in more than two categories of dietary magnesium intake and/or serum magnesium concentrations were included. Random-effects models were used to combine the estimated effects. Nine articles (six on dietary magnesium intake, two on serum magnesium concentration and one on both) of ten cohort studies, including 20,119 cases of hypertension and 180,566 participates, were eligible for inclusion in the meta-analysis. We found an inverse association between dietary magnesium intake and the risk of hypertension [relative risk (RR) = 0.92; 95% CI: 0.86, 0.98] comparing the highest intake group with the lowest. A 100 mg/day increment in magnesium intake was associated with a 5% reduction in the risk of hypertension (RR = 0.95; 95% CI: 0.90, 1.00). The association of serum magnesium concentration with the risk of hypertension was marginally significant (RR = 0.91; 95% CI: 0.80, 1.02). Current evidence supports the inverse dose-response relationship between dietary magnesium intake and the risk of hypertension. However, the evidence about the relationship between serum magnesium concentration and hypertension is limited.

Risk of radiation-induced cancer at low doses and low dose rates for radiation protection purposes

International Nuclear Information System (INIS)

1995-01-01

The aim of this report is to provide an updated, comprehensive review of the data available for assessing the risk of radiation-induced cancer for radiation protection purposes. Particular emphasis is placed on assessing risks at low doses and low dose rates. The review brings together the results of epidemiological investigations and fundamental studies on the molecular and cellular mechanisms involved in radiation damage. Additionally, this information is supplemented by studies with experimental animals which provide further guidance on the form of the dose-response relationship for cancer induction, as well as on the effect of dose rate on the tumour yield. The emphasis of the report is on cancer induction resulting from exposure to radiations with a low linear energy transfer (LET). The work was performed under contract for the Institut de Protection et de Surete Nucleaire, Fontenay-aux-Roses, Paris, France, whose agreement to publish is gratefully ackowledged. It extends the advice on radiation risks given in Documents of the NRPB, 4 No. 4 (1993). (Author)

Frequency-Risk and Duration-Risk Relationships between Aspirin Use and Gastric Cancer: A Systematic Review and Meta-Analysis

Science.gov (United States)

Gao, Yanhui; Liu, Li; Chen, Sidong

2013-01-01

Background Although previous meta-analyses have suggested an association between aspirin use and risk of gastric cancer, current evidence is inconsistent. Additionally, it remains unclear whether there are frequency-risk and duration-risk relationships and if a threshold of effect exists. Methods We identified studies by searching MEDLINE and PUBMED databases and reviewing relevant articles. We derived the summary risk estimates using fixed-effects or random-effects model based on homogeneity analysis. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Potential heterogeneity was tested using the Q statistic and quantified with the I 2 statistic. Subgroup analyses and Galbraith plots were used to explore the potential sources of heterogeneity. Publication bias was evaluated with funnel plots and quantified by the Begg's and Egger's test. Results Fifteen studies were included in this meta-analysis. There was an overall 29% reduced risk of gastric cancer corresponding to aspirin use (RR  = 0.71, 95% CI 0.60–0.82). We found there are nonlinear frequency-risk and linear duration-risk relations between aspirin use and gastric cancer. A monotonically decreasing relation was observed only for low-frequency (≤4.5 times/week) aspirin intake (10% decreased risk for once/week, 19% for twice/week and 29% for 4.5 times/week), and the frequency threshold of aspirin use is 4.5 times per week. Regarding those with duration of aspirin use, there was a tendency towards stronger risk reduction of gastric cancer for longer aspirin use (10% decreased risk for 4 years, 19% for 8 years and 28% for 12 years), and no duration threshold was observed. Conclusion Our findings suggest that long-term (≥4 years) and low-frequency (1–4.5 times per week) aspirin use is associated with a statistically significant, dose-dependent reduction in the risk of gastric cancer. PMID:23936269

Frequency-risk and duration-risk relationships between aspirin use and gastric cancer: a systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Xiaohua Ye

Full Text Available BACKGROUND: Although previous meta-analyses have suggested an association between aspirin use and risk of gastric cancer, current evidence is inconsistent. Additionally, it remains unclear whether there are frequency-risk and duration-risk relationships and if a threshold of effect exists. METHODS: We identified studies by searching MEDLINE and PUBMED databases and reviewing relevant articles. We derived the summary risk estimates using fixed-effects or random-effects model based on homogeneity analysis. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Potential heterogeneity was tested using the Q statistic and quantified with the I (2 statistic. Subgroup analyses and Galbraith plots were used to explore the potential sources of heterogeneity. Publication bias was evaluated with funnel plots and quantified by the Begg's and Egger's test. RESULTS: Fifteen studies were included in this meta-analysis. There was an overall 29% reduced risk of gastric cancer corresponding to aspirin use (RR  = 0.71, 95% CI 0.60-0.82. We found there are nonlinear frequency-risk and linear duration-risk relations between aspirin use and gastric cancer. A monotonically decreasing relation was observed only for low-frequency (≤4.5 times/week aspirin intake (10% decreased risk for once/week, 19% for twice/week and 29% for 4.5 times/week, and the frequency threshold of aspirin use is 4.5 times per week. Regarding those with duration of aspirin use, there was a tendency towards stronger risk reduction of gastric cancer for longer aspirin use (10% decreased risk for 4 years, 19% for 8 years and 28% for 12 years, and no duration threshold was observed. CONCLUSION: Our findings suggest that long-term (≥4 years and low-frequency (1-4.5 times per week aspirin use is associated with a statistically significant, dose-dependent reduction in the risk of gastric cancer.

Exploring Nonlinearities in Financial Systemic Risk

NARCIS (Netherlands)

Wolski, M.

2013-01-01

We propose a new methodology of assessing the effects of individual institution's risk on the others and on the system as a whole. We build upon the Conditional Value-at-Risk approach, however, we introduce the explicit Granger causal linkages and we account for possible nonlinearities in the

Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

Energy Technology Data Exchange (ETDEWEB)

Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

2013-06-01

Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.

Maternal vitamin D status during pregnancy and risk of childhood asthma: A meta-analysis of prospective studies.

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Song, Huihui; Yang, Lei; Jia, Chongqi

2017-05-01

Mounting evidence suggests that maternal vitamin D status during pregnancy may be associated with development of childhood asthma, but the results are still inconsistent. A dose-response meta-analysis was performed to quantitatively summarize evidence on the association of maternal vitamin D status during pregnancy with the risk of childhood asthma. A systematic search was conducted to identify all studies assessing the association of maternal 25-hydroxyvitamin D (25(OH)D) during pregnancy with risk of childhood asthma. The fixed or random-effect model was selected based on the heterogeneity test among studies. Nonlinear dose-response relationship was assessed by restricted cubic spline model. Fifteen prospective studies with 12 758 participants and 1795 cases were included in the meta-analysis. The pooled relative risk of childhood asthma comparing the highest versus lowest category of maternal 25(OH)D levels was 0.87 (95% confidence interval, CI, 0.75-1.02). For dose-response analysis, evidence of a U-shaped relationship was found between maternal 25(OH)D levels and risk of childhood asthma (P nonlinearity = 0.02), with the lowest risk at approximately 70 nmol/L of 25(OH)D. This dose-response meta-analysis suggested a U-shaped relationship between maternal blood 25(OH)D levels and risk of childhood asthma. Further studies are needed to confirm the association. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake.

Science.gov (United States)

Demonty, Isabelle; Ras, Rouyanne T; van der Knaap, Henk C M; Duchateau, Guus S M J E; Meijer, Linsie; Zock, Peter L; Geleijnse, Johanna M; Trautwein, Elke A

2009-02-01

Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.

Dose and diameter relationships for facial, trigeminal, and acoustic neuropathies following acoustic neuroma radiosurgery

International Nuclear Information System (INIS)

Flickinger, John C.; Kondziolka, Douglas; Lunsford, L. Dade

1996-01-01

Purpose and objective: To define the relationships between dose and tumor diameter for the risks of developing trigeminal, facial, and acoustic neuropathies after acoustic neuroma radiosurgery, a large single-institution experience was analyzed. Materials and methods: Two hundred and thirty-eight patients with unilateral acoustic neuromas who underwent Gamma knife radiosurgery between 1987-1994 with 6-91 months of follow-up (median 30 months) were studied. Minimum tumor doses were 12-20 Gy (median 15 Gy). Transverse tumor diameter varied from 0.3-5.5 cm (median 2.1 cm). The relationships of dose and diameter to the development of cranial neuropathies were delineated by multivariate logistic regression. Results: The development of post-radiosurgery neuropathies affecting cranial nerves V, VII, and VIII were correlated with minimum tumor dose and transverse tumor diameter (P min for VIII where P=0.10). A comparison of the dose-diameter response curves showed the acoustic nerve to be the most sensitive to doses of 12-16 Gy and the facial nerve to be the least sensitive. Conclusion: The risks of developing trigeminal, facial, and acoustic neuropathies following acoustic neuroma radiosurgery can be predicted from the transverse tumor diameter and the minimum tumor dose using models constructed from data presently available

Dose-response relationship for life-shortening and carcinogenesis in mice irradiated at day 7 postnatal age with dose range below 1 Gy of gamma rays

International Nuclear Information System (INIS)

Sasaki, Shunsaku; Fukuda, Nobuo

2006-01-01

This study was designed to elucidate the dose-response relationships for life-shortening and tumorigenic effect in the dose range below 1 Gy of gamma rays delivered during the infant period. Female B6C3F 1 mice were irradiated with 0.10, 0.48 or 0.95 Gy at 7 days of age. All irradiated mice were allowed to live out their entire life span together with a simultaneously ongoing control group under a specific pathogen-free condition. Shortening of the mean life span was 1.58% in mice irradiated with 0.10 Gy, which was statistically significant. The coefficient of the linear dose-response relationship for life-shortening was 11.21% Gy -1 . The attributable death fraction for all causes of death in 0.10 Gy group reached 0.092. The excess relative risk for death rate from all causes was 0.102 in the group irradiated with 0.10 Gy. The coefficient of the linear dose-response relationship of the excess relative risk for death rate from all causes was 1.30 Gy -1 . The mean number of types of solid tumors at the time of death in mice irradiated with 0.10 Gy was distinctly larger than that in the control group. The excess relative risk for death rate from solid tumors was 0.45 in mice irradiated with 0.10 Gy. The coefficient of the linear dose-response relationship of excess relative risk for death rate from solid tumors was 4.52 Gy -1 . Increase in incidences of the pituitary, ovarian and adrenal tumors was observed in mice irradiated with 0.10 Gy. The results of the present study showed that infant mice are susceptible to solid tumor induction, especially of the endocrine organs. (author)

The Non-Linear Relationship Between Fiscal Deficits And Inflation: Evidence From Africa

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Abu Nurudeen

2015-12-01

Full Text Available Although, there is abundant research on the fiscal deficit-inflation relationship, little has been done to investigate the non-linear association between them, particularly in Africa. This study employs fixed-effects and GMM estimators to examine the non-linear relationship between deficits and inflation from 1999 to 2011 in 51 African economies, which are further grouped into high-inflation/low-income countries and moderate-inflation/middle-income countries. The results indicate that the deficit-inflation relationship is non-linear for the whole sample and sub-groups. For the whole sample, a percentage point increase in deficit results in a 0.25 percentage point increase in inflation rate, while the relationship becomes quantitatively greater once deficits reach 23% of GDP. The subsamples report different relationships. Although our results cannot be used as the base for generalization, we identify importance of grouping African countries according to their levels of inflation and/or income, rather than treating them as a homogeneous entity.

A system of dose-effects relationships for the Northern wildlife: radiation protection criteria

International Nuclear Information System (INIS)

Sazykina, T.G.

2004-01-01

The key issue in the assessment system for radiation protection of wildlife is the establishment of a set of dose-effects relationships for reference representatives of natural biota, based on scientific data from a range of doses and a range of radiation effects. Risks to natural populations in particular habitats can be evaluated from a comparison of estimated doses to biota with the scale of dose-effects relationships for different types of biota. Within the frame of the EC Project EPIC 'Environmental Protection from Ionizing Contaminants' 2000-2003), a database has been created, which include the published and unpublished data relating to dose effects relationships for flora and fauna in the Northern and Arctic areas. The EPIC database contains information based exclusively on Russian/FSU experimental and field studies; chronic/lifetime exposures were the focus of the work, owing to the fact that such exposures are the most typical in radiological assessments for biota. In total, the EPIC database radiation effects on biota contains about 1600 records from 440 publications, including datasets on terrestrial and aquatic animals, plants, soil fauna and microorganisms. The EPIC database information cover a very wide range of radiation dose rates to wild flora and fauna: from below 10 -5 Gy d -1 up to more than 1 Gy d -1 . A great variety of radiation effects are registered in the EPIC database, from stimulation at low doses up to death from acute radiation syndrome at high doses. From data, compiled in the EPIC database, the dose-effects relationships were derived for different types of northern organisms. The system of dose-effects relationships forms the scale of severity of radiation effects at increasing levels of chronic radiation exposure. With its focus on the effects of low-to-moderate chronic exposure, the system of dose effects relationships provides a useful tool for scientists and decision-makers to establish safety standards for protecting the

Three-dimensional dose-response models of competing risks and natural life span

International Nuclear Information System (INIS)

Raabe, O.G.

1987-01-01

Three-dimensional dose-rate/time/response surfaces for chronic exposure to carcinogens, toxicants, and ionizing radiation dramatically clarify the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. An illustration with computer graphics shows the contributions with the passage of time of the competing risks of death from radiation pneumonitis/fibrosis, lung cancer, and natural aging consequent to the inhalation of plutonium-239 dioxide by beagles. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each fatal effect. Radiation pneumonitis predominates at high dose rates and lung cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for lung cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to the planning and evaluation of epidemiological analyses and experimental studies involving chronic exposure to toxicants

The risk equivalent of an exposure to-, versus a dose of radiation

International Nuclear Information System (INIS)

Bond, V.P.

1986-01-01

The long-term potential carcinogenic effects of low-level exposure (LLE) are addressed. The principal point discussed is linear, no-threshold dose-response curve. That the linear no-threshold, or proportional relationship is widely used is seen in the way in which the values for cancer risk coefficients are expressed - in terms of new cases, per million persons exposed, per year, per unit exposure or dose. This implies that the underlying relationship is proportional, i.e., ''linear, without threshold''. 12 refs., 9 figs., 1 tab

Imaging dose in breast radiotherapy: does breast size affect the dose to the organs at risk and the risk of secondary cancer to the contralateral breast?

International Nuclear Information System (INIS)

Batumalai, Vikneswary; Quinn, Alexandra; Jameson, Michael; Delaney, Geoff; Holloway, Lois

2015-01-01

Correct target positioning is crucial for accurate dose delivery in breast radiotherapy resulting in utilisation of daily imaging. However, the radiation dose from daily imaging is associated with increased probability of secondary induced cancer. The aim of this study was to quantify doses associated with three imaging modalities and investigate the correlation of dose and varying breast size in breast radiotherapy. Planning computed tomography (CT) data sets of 30 breast cancer patients were utilised to simulate the dose received by various organs from a megavoltage computed tomography (MV-CT), megavoltage electronic portal image (MV-EPI) and megavoltage cone-beam computed tomography (MV-CBCT). The mean dose to organs adjacent to the target volume (contralateral breast, lungs, spinal cord and heart) were analysed. Pearson correlation analysis was performed to determine the relationship between imaging dose and primary breast volume and the lifetime attributable risk (LAR) of induced secondary cancer was calculated for the contralateral breast. The highest contralateral breast mean dose was from the MV-CBCT (1.79 Gy), followed by MV-EPI (0.22 Gy) and MV-CT (0.11 Gy). A similar trend was found for all organs at risk (OAR) analysed. The primary breast volume inversely correlated with the contralateral breast dose for all three imaging modalities. As the primary breast volume increases, the likelihood of a patient developing a radiation-induced secondary cancer to the contralateral breast decreases. MV-CBCT showed a stronger relationship between breast size and LAR of developing a radiation-induced contralateral breast cancer in comparison with the MV-CT and MV-EPI. For breast patients, imaging dose to OAR depends on imaging modality and treated breast size. When considering the use of imaging during breast radiotherapy, the patient's breast size and contralateral breast dose should be taken into account

Comparison of the dose-effect relationship for UV radiation and ionizing radiation

International Nuclear Information System (INIS)

Leenhouts, H.P.; Sijsma, M.J.; Chadwick, K.H.

1990-06-01

Ionizing radiation and ultraviolet radiation (UV) are both physical agents with mutagenic and carcinogenic properties. However, there are some basic differences in the fundamental mechanism of their interaction with biological material that may have consequences for risk assessment. In this paper the dose-effect relationships for gamma radiation and UV at cellular level will be used to demonstrate the different radio-biological effectiveness of both agents. The results will be discussed in the framework of a biophysical model, based on the assumption that DNA doublestranded lesions are crucial for the cytotoxic action. After exposure to ionizing radiation, the lesions are fixed immediately following irradiation, but after UV exposure the lethal lesions are recognized only in the next DNA synthesis phase. The combination of this concept with the mechanism of lesion induction and the possibility of repair, leads to different dose and time relationships for the radiation effects of both agents. The possible consequences for risk assessment at low levels will be discussed. (author). 9 refs.; 5 figs

The scientific basis for the establishment of threshold levels and dose response relationships of carcinogenesis

International Nuclear Information System (INIS)

1975-01-01

The International Atomic Energy Agency hosted a two day Symposium from 2-3 December 1974 at its Headquarters, organized by the 'International Academy for Environmental Safety and the Forum fur Wissenschaft, Wirtschaft und Politik' on the subject 'Scientific Basis for the Establishment of Threshold. Levels and Dose Response Relationships of Carcinogenesis'. Following an introductory paper by the Radiation Biology Section of the Agency on 'Radiation Carcinogenesis - Dose Response Relationship, Threshold and Risk Estimates', a series of papers dealt with this problem in chemical carcinogenesis.It was suggested that more experiments should be done using non-human primates for tests of carcinogens, especially chemicals. Preliminary experiments using monkeys with a potent carcinogen - nitrosoamine - indicate that there could possibly be a dose where no effect can be observed during the 5 year period of study. It was also pointed out that the overall cost/benefit and risk/ benefit relationships should be taken into consideration in determining limits for chemicals which are potentially carcinogenic but are used routinely by the public and industries; these considerations have been weighed in setting exposure limits for radiation

Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses.

Science.gov (United States)

Samokhvalov, Andriy V; Rehm, Jürgen; Roerecke, Michael

2015-12-01

Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose-response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose-response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60-0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69-1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04-13.02). The dose-response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author.

Quantifying the dose-response relationship between circulating folate concentrations and colorectal cancer in cohort studies: a meta-analysis based on a flexible meta-regression model.

Science.gov (United States)

Chuang, Shu-Chun; Rota, Matteo; Gunter, Marc J; Zeleniuch-Jacquotte, Anne; Eussen, Simone J P M; Vollset, Stein Emil; Ueland, Per Magne; Norat, Teresa; Ziegler, Regina G; Vineis, Paolo

2013-10-01

Most epidemiologic studies on folate intake suggest that folate may be protective against colorectal cancer, but the results on circulating (plasma or serum) folate are mostly inconclusive. We conducted a meta-analysis of case-control studies nested within prospective studies on circulating folate and colorectal cancer risk by using flexible meta-regression models to test the linear and nonlinear dose-response relationships. A total of 8 publications (10 cohorts, representing 3,477 cases and 7,039 controls) were included in the meta-analysis. The linear and nonlinear models corresponded to relative risks of 0.96 (95% confidence interval (CI): 0.91, 1.02) and 0.99 (95% CI: 0.96, 1.02), respectively, per 10 nmol/L of circulating folate in contrast to the reference value. The pooled relative risks when comparing the highest with the lowest category were 0.80 (95% CI: 0.61, 0.99) for radioimmunoassay and 1.03 (95% CI: 0.83, 1.22) for microbiological assay. Overall, our analyses suggest a null association between circulating folate and colorectal cancer risk. The stronger association for the radioimmunoassay-based studies could reflect differences in cohorts and study designs rather than assay performance. Further investigations need to integrate more accurate measurements and flexible modeling to explore the effects of folate in the presence of genetic, lifestyle, dietary, and hormone-related factors.

Dynamical System and Nonlinear Regression for Estimate Host-Parasitoid Relationship

Directory of Open Access Journals (Sweden)

Ileana Miranda Cabrera

2010-01-01

Full Text Available The complex relationships of a crop with the pest, its natural enemies, and the climate factors exist in all the ecosystems, but the mathematic models has studied only some components to know the relation cause-effect. The most studied system has been concerned with the relationship pest-natural enemies such as prey-predator or host-parasitoid. The present paper shows a dynamical system for studying the relationship host-parasitoid (Diaphorina citri, Tamarixia radiata and shows that a nonlinear model permits the estimation of the parasite nymphs using nymphs healthy as the known variable. The model showed the functional answer of the parasitoid, in which a point arrives that its density is not augmented although the number host increases, and it becomes necessary to intervene in the ecosystem. A simple algorithm is used to estimate the parasitoids level using the priori relationship between the host and the climate factors and then the nonlinear model.

Simulation of the Nonlinear Dose Dependence of Stabilized Point Defects

International Nuclear Information System (INIS)

Chen, R; Pagonis, V; Lawless, J L

2010-01-01

The dose dependence of the concentration of point defects in alkali-halides as well as other crystals, as exhibited by the dependence of the thermoluminescence (TL), optical absorption and ESR on the dose of non-ionizing UV excitation is studied using numerical simulation. The relevant set of coupled rate equations are first written and plausible sets of trapping parameters are chosen. Instead of using simplifying assumptions previously used for reaching conclusions concerning this dose behavior, exact numerical solutions have now been reached. Depending on the parameters chosen, different dose dependencies are seen. In some cases, linear dose dependence is reached in a broad range. Sublinear dose dependence, close to a D 1/2 dependence when D is the dose of excitation can be reached when retrapping is stronger than trapping in other traps stabilizing the defects. When strong competition between stabilizing traps takes place, an initial linear range is observed followed by strong superlinearity and an approach to saturation. All these behaviors have been observed experimentally in TL measurements as well as ESR and optical absorption in different materials. Similarities and dissimilarities to linear and non-linear dose dependencies obtained experimentally and by simulations when ionizing irradiation is used for excitation are discussed.

Linearity and Nonlinearity in HIV/STI Transmission: Implications for the Evaluation of Sexual Risk Reduction Interventions

Science.gov (United States)

Pinkerton, Steven D.; Chesson, Harrell W.; Crosby, Richard A.; Layde, Peter M.

2011-01-01

A mathematical model of HIV/sexually transmitted infections (STI) transmission was used to examine how linearity or nonlinearity in the relationship between the number of unprotected sex acts (or the number of sex partners) and the risk of acquiring HIV or a highly infectious STI (such as gonorrhea or chlamydia) affects the utility of sexual…

Dose-Response—A Challenge for Allelopathy?

Science.gov (United States)

Belz, Regina G.; Hurle, Karl; Duke, Stephen O.

2005-01-01

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions. PMID:19330161

Dose-response-a challenge for allelopathy?

Science.gov (United States)

Belz, Regina G; Hurle, Karl; Duke, Stephen O

2005-04-01

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.

Dose-response relationship in clinical oncology

International Nuclear Information System (INIS)

Gehan, E.A.

1984-01-01

The relationship of dose (and dose rate) to response and toxicity in clinical oncology is reviewed. The concepts expressed by some authors in dose-response studies in animal and human systems are reviewed briefly. Dose rate and tactics of conducting clinical studies are reviewed for both radiotherapy and various types of chemotherapeutic treatment. Examples are given from clinical studies in Hodgkin's disease, acute leukemia, and breast cancer that may prove useful in planning future clinical studies

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

International Nuclear Information System (INIS)

Bender, Edward T.

2012-01-01

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when compared the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.

Evaluating correlation between geometrical relationship and dose difference caused by respiratory motion using statistical analysis

Energy Technology Data Exchange (ETDEWEB)

Shin, Dong Seok; Kim, Dong Su; Kim, Tae Ho; Kim, Kyeong Hyeon; Yoon, Do Kun; Suh, Tae Suk [The Catholic University of Korea, Seoul (Korea, Republic of); Kang, Seong Hee [Seoul National University Hospital, Seoul (Korea, Republic of); Cho, Min Seok [Asan Medical Center, Seoul (Korea, Republic of); Noh, Yu Yoon [Eulji University Hospital, Daejeon (Korea, Republic of)

2017-04-15

Three-dimensional dose (3D dose) can consider coverage of moving target, however it is difficult to provide dosimetric effect which occurs by respiratory motions. Four-dimensional dose (4D dose) which uses deformable image registration (DIR) algorithm from four-dimensional computed tomography (4DCT) images can consider dosimetric effect by respiratory motions. The dose difference between 3D dose and 4D dose can be varied according to the geometrical relationship between a planning target volume (PTV) and an organ at risk (OAR). The purpose of this study is to evaluate the correlation between the overlap volume histogram (OVH), which quantitatively shows the geometrical relationship between the PTV and OAR, and the dose differences. In conclusion, no significant statistical correlation was found between the OVH and dose differences. However, it was confirmed that a higher difference between the 3D and 4D doses could occur in cases that have smaller OVH value. No significant statistical correlation was found between the OVH and dose differences. However, it was confirmed that a higher difference between the 3D and 4D doses could occur in cases that have smaller OVH value.

Dose-response relationship analysis for cancer and circulatory system disease mortality risks among uranium miners

International Nuclear Information System (INIS)

Drubay, Damien

2015-01-01

The relation between lung cancer risk and radon exposure has been clearly established, especially from the studies on uranium miner cohorts. But the association between radon exposure and extrapulmonary cancers and non-cancer diseases remains not well known. Moreover, the health risks associated with the other mining-related ionizing radiation exposures are still under consideration. The aim of this thesis is to contribute to the estimation of the radio-induced health risks at low-doses through the analysis of the kidney cancer and Circulatory System Disease (CSD) mortality risks among uranium miners. Kidney cancer mortality risk analyses were performed from the French cohort of uranium miners (n=5086; follow-up period: 1946-2007), the post-55 cohort (n=3,377; follow-up period: 1957-2007) and the German cohort of the Wismut (n=58,986; follow-up period: 1946-2003) which included 24, 11 and 174 deaths from kidney cancer, respectively. The exposures to radon and its short-lived progeny (expressed in Working Level Month WLM), to uranium ore dust (kBqh.m -3 ) and to external gamma rays (mSv) were estimated for each miners and the equivalent kidney dose was calculated. The dose-response relation was refined considering two responses: the instantaneous risk of kidney cancer mortality (corresponding to the classical analysis, Cause specific Hazard Ratio (CSHR) estimated with the Cox model) and its occurrence probability during the followup (Sub-distribution Hazard Ratio (SHR) estimated with the Fine and Gray model). An excess of kidney cancer mortality was observed only in the French cohort (SMR = 1.62 CI95%[1.04; 2.41]). In the Wismut cohort, a decrease of the kidney cancer mortality was observed (0.89 [0.78; 0.99]). For these three cohorts, the occupational radiological exposures (or the equivalent kidney dose) were significantly associated neither with the risk of kidney cancer mortality (e.g. CSHRWismut-radon/100 WLM=1.023 [0.993; 1.053]), nor with its occurrence

Exchange Rate – Relative Price Nonlinear Cointegration Relationship in Malaysia

OpenAIRE

Venus Khim-Sen Liew; Chee-Keong Choong; Evan Lau; Kian-Ping Lim

2005-01-01

The finding of exchange rate–relative price nonlinear cointegration relationship in Malaysia, among others, suggests that nonlinear Purchasing Power Parity (PPP) equilibrium may be regarded as reference point in judging the short run misalignment of the Ringgit currency and thereby deducing effective policy actions. Moreover, economists who wish to extend the simple PPP exchange rate model into the more complicated monetary exchange models may do so comfortably, at least in the text of Malays...

An explanation for the multiplicative and the additive dose-effect relationship with the single-hit model

International Nuclear Information System (INIS)

Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

1997-01-01

For solid tumors and for leukemia the excess cancer rate after a single radiation dose D is different. The multiplicative model describes the excess solid tumor probability rate which is proportional to the background rate of cancer and dependent on dose D. The additive model describes the excess probability rate for leukaemia which is proportional to the dose D but unrelated to the spontaneous rate of cancer. A second great difference between the two models is the duration of the increased cancer probability rate. The multiplicative mode predicts that the additional cancer risk persist the whole lifetime after exposure and the additive model predicts excess risk over a period of time. With the Single-hit model (SHM) which is a multistage cancer model both dose-response relationships can be described. It will be shown that only small differences in the derivation will lead to the different relationships. We then analyze the incidence data of leukemia (1950-1987) and of all solid tumors (1958-1987) of the atomic bomb survivors. (author)

Dose and effect relationship of radiation induced cancer and its influencing factors in experimental animals, 1

International Nuclear Information System (INIS)

Sasaki, Shunsaku; Sato, Fumiaki; Eto, Hideo

1975-01-01

The data of risk evaluation of external irradiation were integrated with animal experiments from the aspects of qualitative generalizations of characteristics of radiation induced tumors. Studies covered competition of cause of death, figure of dose-to-effect relationship, characteristics of low dose rate of irradiation, relative biological effectiveness (RBE) of high LET radiation, effects of feactionated irradiation, complex actions with chemical substances, effects of protectional medium, differences of radiosensitivity by species and strains, and age dependency of sensitivities. Competition of cause of death by time length of latent period and degree of malignancy of the disease. Discussion on competition of death suggested the following idea: 1) incidence of tumor induction in the individual level did not correspond to transformation in the cellular level, and 2) relative incidence of tumor induction after a certain dose of whole body irradiation did not indicate the relative sensitivity of each tissue, for the relationship between tumor incidence and exposure dose was not a linear relationship. The dose-to-effect relationship of tumor induction was decided by following factors: i) sensitivity on transformation of cells, ii) sensitivity on the death of potential tumor cells, and iii) competition of the cause of death. Tumor induction by low dose rate irradiation was also studied by comparing qualitative and quantitative differences between high dose rate single irradiation and a series of low dose rate irradiation. (Serizawa, K.)

Generalized Fragility Relationships with Local Site Conditions for Probabilistic Performance-based Seismic Risk Assessment of Bridge Inventories

Directory of Open Access Journals (Sweden)

Sivathayalan S.

2012-01-01

Full Text Available The current practice of detailed seismic risk assessment cannot be easily applied to all the bridges in a large transportation networks due to limited resources. This paper presents a new approach for seismic risk assessment of large bridge inventories in a city or national bridge network based on the framework of probabilistic performance based seismic risk assessment. To account for the influences of local site effects, a procedure to generate site-specific hazard curves that includes seismic hazard microzonation information has been developed for seismic risk assessment of bridge inventories. Simulated ground motions compatible with the site specific seismic hazard are used as input excitations in nonlinear time history analysis of representative bridges for calibration. A normalizing procedure to obtain generalized fragility relationships in terms of structural characteristic parameters of bridge span and size and longitudinal and transverse reinforcement ratios is presented. The seismic risk of bridges in a large inventory can then be easily evaluated using the normalized fragility relationships without the requirement of carrying out detailed nonlinear time history analysis.

TU-C-18A-01: Models of Risk From Low-Dose Radiation Exposures: What Does the Evidence Say?

International Nuclear Information System (INIS)

Bushberg, J; Boreham, D; Ulsh, B

2014-01-01

At dose levels of (approximately) 500 mSv or more, increased cancer incidence and mortality have been clearly demonstrated. However, at the low doses of radiation used in medical imaging, the relationship between dose and cancer risk is not well established. As such, assumptions about the shape of the dose-response curve are made. These assumptions, or risk models, are used to estimate potential long term effects. Common models include 1) the linear non-threshold (LNT) model, 2) threshold models with either a linear or curvilinear dose response above the threshold, and 3) a hormetic model, where the risk is initially decreased below background levels before increasing. The choice of model used when making radiation risk or protection calculations and decisions can have significant implications on public policy and health care decisions. However, the ongoing debate about which risk model best describes the dose-response relationship at low doses of radiation makes informed decision making difficult. This symposium will review the two fundamental approaches to determining the risk associated with low doses of ionizing radiation, namely radiation epidemiology and radiation biology. The strengths and limitations of each approach will be reviewed, the results of recent studies presented, and the appropriateness of different risk models for various real world scenarios discussed. Examples of well-designed and poorly-designed studies will be provided to assist medical physicists in 1) critically evaluating publications in the field and 2) communicating accurate information to medical professionals, patients, and members of the general public. Equipped with the best information that radiation epidemiology and radiation biology can currently provide, and an understanding of the limitations of such information, individuals and organizations will be able to make more informed decisions regarding questions such as 1) how much shielding to install at medical facilities, 2) at

TU-C-18A-01: Models of Risk From Low-Dose Radiation Exposures: What Does the Evidence Say?

Energy Technology Data Exchange (ETDEWEB)

Bushberg, J [UC Davis Medical Center, Sacramento, CA (United States); Boreham, D [McMaster University, Ontario, CA (Canada); Ulsh, B

2014-06-15

At dose levels of (approximately) 500 mSv or more, increased cancer incidence and mortality have been clearly demonstrated. However, at the low doses of radiation used in medical imaging, the relationship between dose and cancer risk is not well established. As such, assumptions about the shape of the dose-response curve are made. These assumptions, or risk models, are used to estimate potential long term effects. Common models include 1) the linear non-threshold (LNT) model, 2) threshold models with either a linear or curvilinear dose response above the threshold, and 3) a hormetic model, where the risk is initially decreased below background levels before increasing. The choice of model used when making radiation risk or protection calculations and decisions can have significant implications on public policy and health care decisions. However, the ongoing debate about which risk model best describes the dose-response relationship at low doses of radiation makes informed decision making difficult. This symposium will review the two fundamental approaches to determining the risk associated with low doses of ionizing radiation, namely radiation epidemiology and radiation biology. The strengths and limitations of each approach will be reviewed, the results of recent studies presented, and the appropriateness of different risk models for various real world scenarios discussed. Examples of well-designed and poorly-designed studies will be provided to assist medical physicists in 1) critically evaluating publications in the field and 2) communicating accurate information to medical professionals, patients, and members of the general public. Equipped with the best information that radiation epidemiology and radiation biology can currently provide, and an understanding of the limitations of such information, individuals and organizations will be able to make more informed decisions regarding questions such as 1) how much shielding to install at medical facilities, 2) at

Topics on study of low dose-effect relationship

Energy Technology Data Exchange (ETDEWEB)

Yamada, Takeshi [Toho Univ., School of Medicine, Tokyo (Japan); Ohyama, Harumi

1999-09-01

It is not exceptional but usually observed that a dose-effect relationship in biosystem is not linear. Sometimes, the low dose-effect relationship appears entirely contrary to the expectation from high dose-effect. This is called a 'hormesis' phenomena. A high dose irradiation inflicts certainly an injury on biosystem. No matter how low the dose may be, an irradiation might inflict some injury on biosystem according to Linear Non-Threshold hypothesis(LNT). On the contrary to the expectation, a low dose irradiation stimulates immune system, and promotes cell proliferation. This is called 'radiation hormesis'. The studies of the radiation hormesis are made on from four points of view as follows: (1) radiation adaptive response, (2) revitalization caused by a low dose stimulation, (3) a low dose response unexpected from the LNT hypothesis, (4) negation of the LNT hypothesis. The various empirical proofs of radiation hormesis are introduced in the report. (M . Suetake)

Topics on study of low dose-effect relationship

International Nuclear Information System (INIS)

Yamada, Takeshi; Ohyama, Harumi

1999-01-01

It is not exceptional but usually observed that a dose-effect relationship in biosystem is not linear. Sometimes, the low dose-effect relationship appears entirely contrary to the expectation from high dose-effect. This is called a 'hormesis' phenomena. A high dose irradiation inflicts certainly an injury on biosystem. No matter how low the dose may be, an irradiation might inflict some injury on biosystem according to Linear Non-Threshold hypothesis(LNT). On the contrary to the expectation, a low dose irradiation stimulates immune system, and promotes cell proliferation. This is called 'radiation hormesis'. The studies of the radiation hormesis are made on from four points of view as follows: (1) radiation adaptive response, (2) revitalization caused by a low dose stimulation, (3) a low dose response unexpected from the LNT hypothesis, (4) negation of the LNT hypothesis. The various empirical proofs of radiation hormesis are introduced in the report. (M . Suetake)

Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies.

Science.gov (United States)

Aune, Dagfinn; Norat, Teresa; Romundstad, Pål; Vatten, Lars J

2013-11-01

Several studies have suggested a protective effect of intake of whole grains, but not refined grains on type 2 diabetes risk, but the dose-response relationship between different types of grains and type 2 diabetes has not been established. We conducted a systematic review and meta-analysis of prospective studies of grain intake and type 2 diabetes. We searched the PubMed database for studies of grain intake and risk of type 2 diabetes, up to June 5th, 2013. Summary relative risks were calculated using a random effects model. Sixteen cohort studies were included in the analyses. The summary relative risk per 3 servings per day was 0.68 (95% CI 0.58-0.81, I(2) = 82%, n = 10) for whole grains and 0.95 (95% CI 0.88-1.04, I(2) = 53%, n = 6) for refined grains. A nonlinear association was observed for whole grains, p nonlinearity cereals, wheat bran and brown rice, but these results were based on few studies, while white rice was associated with increased risk. Our meta-analysis suggests that a high whole grain intake, but not refined grains, is associated with reduced type 2 diabetes risk. However, a positive association with intake of white rice and inverse associations between several specific types of whole grains and type 2 diabetes warrant further investigations. Our results support public health recommendations to replace refined grains with whole grains and suggest that at least two servings of whole grains per day should be consumed to reduce type 2 diabetes risk.

Critical reevaluation of the dose-response relationships for carcinogenic effects of low-level ionizing radiation

International Nuclear Information System (INIS)

Upton, A.C.

2003-01-01

In recent decades, it has been customary, for radiation protection purposes, to assume that the overall risk of radiation-induced cancer increases as a linear-nonthreshold function of the dose. The existing data do not exclude the existence of a threshold, however, and the dose-response relationship is known to vary, depending on the type of cancer in queation, the dose, dose rate, and LET of the radiation, the age, sex, and physiological state of the exposed individuals, and other variables, including the potential influence of adaptive responses and bystander effects at low doses. In light of advncing knowledge, therefore, the dose-response relationship for carcinogenic effects of low-level radiation has been reevaluated periodically by the National Council on Radiation Protection and Measurements, the International Commission of Radiological Protection, the United Nations Scientific Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences, and other organizations. The most recent such reviews have generally found the weight of evidence to suggest that lesions which are precursors to cancer (i.e., mutations and chromosome aberrations), and certain types of cancer as well, may increase in frequency linearly with the dose in the low-dose domain. On this basis, it is concluded that no alternative dose-response model for the carcinogenic effects of low-level radiation is more plausible than the linear-nonthreshold model, although other dose-response relationships cannot be excluded. (authors)

Dose-Effect Relationships for Individual Pelvic Floor Muscles and Anorectal Complaints After Prostate Radiotherapy

International Nuclear Information System (INIS)

Smeenk, Robert Jan; Hoffmann, Aswin L.; Hopman, Wim P.M.; Lin, Emile N.J. Th. van; Kaanders, Johannes H.A.M.

2012-01-01

Purpose: To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate radiotherapy (RT). Methods and Materials: In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed. Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated. Results: The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: ≤30 Gy to the IAS; ≤10 Gy to the EAS; ≤50 Gy to the PRM; and ≤40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles. Conclusions: Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are

Dose-effect relationships for individual pelvic floor muscles and anorectal complaints after prostate radiotherapy.

Science.gov (United States)

Smeenk, Robert Jan; Hoffmann, Aswin L; Hopman, Wim P M; van Lin, Emile N J Th; Kaanders, Johannes H A M

2012-06-01

To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate radiotherapy (RT). In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed. Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated. The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: ≤ 30 Gy to the IAS; ≤ 10 Gy to the EAS; ≤ 50 Gy to the PRM; and ≤ 40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles. Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are excluded. Copyright © 2012 Elsevier Inc. All rights

The statistics of dose/cure relationships for irradiated tumours

International Nuclear Information System (INIS)

Porter, E.H.

1980-01-01

Consideration is given to the theoretical effects of different factors on the form of dose/cure relationships. Single-clonogen recurrences, dominant anoxic fractions, asymptotically straight survival curves, variable tumour sizes and variable radiation doses are all discussed. Statistical methods are then reviewed, and the conclusions are summarized in the form of advice to experimenters who are studying dose/cure relationships. (UK)

Relationship between mutation frequency of GPA locus and cumulative dose among medical diagnostic X-ray workers

International Nuclear Information System (INIS)

Wang Jixian; Yu Wenru; Li Benxiao; Fan Tiqiang; Li Zhen; Gao Zhiwei; Chen Zhenjun; Zhao Yongcheng

2000-01-01

Objective: To explore the feasibility of using GPA locus mutation assay as a bio-dosimeter for occupational exposure to ionizing radiation. Methods: An improved technique of GPA locus mutation assay was used in th study. The frequencies of mutant RBC in peripheral blood of 55 medical X-ray workers and 50 controls employed in different calendar-year periods were detected. The relationship between mutation frequencies (MFs) and period of entry, working years and cumulative doses were analyzed. Results: The MFs were significantly elevated among X-ray workers employed before 1970. This finding is similar to the result of cancer epidemiological study among medical X-ray workers , in which the cancer risk was significantly increased only X-ray workers employed before 1970. The MFs of GPA increased with increasing cumulative dose. The dose-effect relationship of Nφ MF with cumulative dose was closer than that of NN MF. Conclusion: There are many problems to be solved for using GPA MF assay as a bio-dosimeter such as individual variation, specificity and calibration curve of dose-effect relationship

Nonlinear image blending for dual-energy MDCT of the abdomen: can image quality be preserved if the contrast medium dose is reduced?

Science.gov (United States)

Mileto, Achille; Ramirez-Giraldo, Juan Carlos; Marin, Daniele; Alfaro-Cordoba, Marcela; Eusemann, Christian D; Scribano, Emanuele; Blandino, Alfredo; Mazziotti, Silvio; Ascenti, Giorgio

2014-10-01

The objective of this study was to compare the image quality of a dual-energy nonlinear image blending technique at reduced load of contrast medium with a simulated 120-kVp linear blending technique at a full dose during portal venous phase MDCT of the abdomen. Forty-five patients (25 men, 20 women; mean age, 65.6 ± 9.7 [SD] years; mean body weight, 74.9 ± 12.4 kg) underwent contrast-enhanced single-phase dual-energy CT of the abdomen by a random assignment to one of three different contrast medium (iomeprol 400) dose injection protocols: 1.3, 1.0, or 0.65 mL/kg of body weight. The contrast-to-noise ratio (CNR) and noise at the portal vein, liver, aorta, and kidney were compared among the different datasets using the ANOVA. Three readers qualitatively assessed all datasets in a blinded and independent fashion. Nonlinear blended images at a 25% reduced dose allowed a significant improvement in CNR (p < 0.05 for all comparisons), compared with simulated 120-kVp linear blended images at a full dose. No statistically significant difference existed in CNR and noise between the nonlinear blended images at a 50% reduced dose and the simulated 120-kVp linear blended images at a full dose. Nonlinear blended images at a 50% reduced dose were considered in all cases to have acceptable image quality. The dual-energy nonlinear image blending technique allows reducing the dose of contrast medium up to 50% during portal venous phase imaging of the abdomen while preserving image quality.

The Dose-Volume Relationship of Small Bowel Irradiation and Acute Grade 3 Diarrhea During Chemoradiotherapy for Rectal Cancer

International Nuclear Information System (INIS)

Robertson, John M.; Lockman, David; Yan Di; Wallace, Michelle

2008-01-01

Purpose: Previous work has found a highly significant relationship between the irradiated small-bowel volume and development of Grade 3 small-bowel toxicity in patients with rectal cancer. This study tested the previously defined parameters in a much larger group of patients. Methods and Materials: A total of 96 consecutive patients receiving pelvic radiation therapy for rectal cancer had treatment planning computed tomographic scans with small-bowel contrast that allowed the small bowel to be outlined with calculation of a small-bowel dose-volume histogram for the initial intended pelvic treatment to 45 Gy. Patients with at least one parameter above the previously determined dose-volume parameters were considered high risk, whereas those with all parameters below these levels were low risk. The grade of diarrhea and presence of liquid stool was determined prospectively. Results: There was a highly significant association with small-bowel dose-volume and Grade 3 diarrhea (p ≤ 0.008). The high-risk and low-risk parameters were predictive with Grade 3 diarrhea in 16 of 51 high-risk patients and in 4 of 45 low-risk patients (p = 0.01). Patients who had undergone irradiation preoperatively had a lower incidence of Grade 3 diarrhea than those treated postoperatively (18% vs. 28%; p = 0.31); however, the predictive ability of the high-risk/low-risk parameters was better for preoperatively (p = 0.03) than for postoperatively treated patients (p = 0.15). Revised risk parameters were derived that improved the overall predictive ability (p = 0.004). Conclusions: The highly significant dose-volume relationship and validity of the high-risk and low-risk parameters were confirmed in a large group of patients. The risk parameters provided better modeling for the preoperative patients than for the postoperative patients

Critical reevaluation of the dose-response relationships for carcinogenic effects of low-level ionizing radiation

International Nuclear Information System (INIS)

Upton, Arthur C.

2002-01-01

In recent decades, it has been customary, for radiation protection purposes, to assume that the overall risk of radiation- included cancer increases as a linear-nonthreshold function of the dose. The existing data do not exclude the existence of a threshold, however, and the dose-response relationship is known to vary depending on the type of cancer in question, the dose, dose rate and LET of the radiation, the age, sex and physiological state of the exposed individuals, and other variables, including the potential influence of adaptive responses and bystander effects at low doses. In light of advancing knowledge, therefore, the dose-response relationship for carcinogenic effects of low-level radiation has been reevaluated periodically by the National Council on Radiation Protection and Measurements, the International Commission of Radiological Protection, the United Nations Scientific Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences, and other organizations. The most recent such reviews have generally found the weight of evidence to suggest that lesions which are precursors to cancer (i.e., mutations and chromosome aberrations), and certain types of cancer as well, may increase in frequency linearly aberrations), and certain types of cancer as well, may increase in frequency linearly with the dose in the low-dose domain. On this basis, it is concluded that no alternative dose-response model for the carcinogenic effects of low-level radiation is ore plausible than the linear-nonthreshold model, although other dose-response relationships cannot be excluded. (author)

Comparison of the dose-response relationships for chromosome aberration frequencies between the T65D and DS86 dosimetries

International Nuclear Information System (INIS)

Preston, D.L.; McConney, M.E.; Awa, A.A.; Ohtaki, Kazuo; Itoh, Masahiro; Honda, Takeo.

1989-05-01

Cytogenetic data, derived from cultured lymphocytes of atomic bomb survivors and controls in the ABCC-RERF Adult Health Study cohort, have been analyzed to determine differences in the dose-response relationships for chromosome aberrations between the T65D and DS86 dose estimates and to assess differences between Hiroshima and Nagasaki. For a linear dose-response model, the average percentage of cells with at least one chromosome aberration increases less rapidly with dose in Nagasaki than in Hiroshima. The magnitude of the intercity difference in the percentage of cells with aberrations per gray is less for DS86 than for T65D, though the difference is statistically significant for both kerma and bone marrow dose with either dosimetry. The percentage of cells with aberrations per gray for DS86 kerma estimates is about 60 % greater than the corresponding T65D slope. Analyses to test nonlinearity in the dose-response function indicate significant departures (p<.001) from linearity, using both dosimetries for both kerma and marrow dose. Therefore, comparative results are presented for a range of RBE relationships under various linear (L) and linearquadratic linear (LQ-L) models. As an illustrative result, if one assumes an LQ-L model similar to models reported in the cytogenetic literature, with a limiting RBE of 20 at zero dose, the DS86 slope (the percentage of cells with aberrations per sievert) is 120 % greater than the corresponding T65D value. (J.P.N.)

Physical activity and the risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis of epidemiological studies.

Science.gov (United States)

Aune, Dagfinn; Sen, Abhijit; Henriksen, Tore; Saugstad, Ola Didrik; Tonstad, Serena

2016-10-01

Physical activity has been inconsistently associated with risk of gestational diabetes mellitus in epidemiological studies, and questions remain about the strength and shape of the dose-response relationship between the two. We therefore conducted a systematic review and meta-analysis of cohort studies and randomized trials on physical activity and gestational diabetes mellitus. PubMed, Embase and Ovid databases were searched for cohort studies, and randomized controlled trials of physical activity and risk of gestational diabetes mellitus, up to August 5th 2015. Summary relative risks (RRs) were estimated using a random effects model. Twenty-five studies (26 publications) were included. For total physical activity the summary RR for high versus low activity was 0.62 (95 % CI 0.41-0.94, I 2  = 0 %, n = 4) before pregnancy, and 0.66 (95 % CI 0.36-1.21, I 2  = 0 %, n = 3) during pregnancy. For leisure-time physical activity the respective summary RRs for high versus low activity was 0.78 (95 % CI 0.61-1.00, I 2  = 47 %, n = 8) before pregnancy, and it was 0.80 (95 % CI 0.64-1.00, I 2  = 17 %, n = 17) during pregnancy. The summary RR for pre-pregnancy activity was 0.70 (95 % CI 0.49-1.01, I 2  = 72.6 %, n = 3) per increment of 5 h/week and for activity during pregnancy was 0.98 (95 % CI 0.87-1.09, I 2  = 0 %, n = 3) per 5 h/week. There was evidence of a nonlinear association between physical activity before pregnancy and the risk of gestational diabetes mellitus, p nonlinearity  = 0.005, with a slightly steeper association at lower levels of activity although further reductions in risk were observed up to 10 h/week. There was also evidence of nonlinearity for physical activity in early pregnancy, p nonlinearity  = 0.008, with no further reduction in risk above 8 h/week. There was some indication of inverse associations between walking (before and during pregnancy) and vigorous activity (before pregnancy) and the risk of

Estimation of breast doses and breast cancer risk associated with repeated fluoroscopic chest examinations of women with tuberculosis

International Nuclear Information System (INIS)

Boice, J.D. Jr.; Rosenstein, M.; Trout, E.D.

1978-01-01

A methodology is presented to estimate cumulative breast dose and breast cancer risk for women exposed to repeated fluoroscopic chest examinations during air collapse therapy for pulmonary tuberculosis. Medical record abstraction, physician interview, patient contact, machine exposure measurements, and absorbed dose computations were combined to estimate average breast doses for 1047 Massachusetts women who were treated between 1930 and 1954. The methodology presented considers breast size and composition, patient orientation, x-ray field size and location, beam quality, type of examination, machine exposure rate, and exposure time during fluoroscopic examinations. The best estimate for the risk of radiation-induced cancer for the women living longer than 10 years after initial fluoroscopic exposure is 6.2 excess breast cancers per million woman-year-rad with 90% confidence limits of 2.8 and 10.7 cancers/10 6 WY-rad. When breast cancer risk is considered as a function of absorbed dose in the breast, instead of as a function of the number of fluoroscopic examinations, a linear dose--response relationship over the range of estimated doses is consistent with the data. However, because of the uncertainty due to small-sample variability and because of the wide range of assumptions regarding certain fluoroscopy conditions, other dose--response relationships are compatible with the data

Non-linear dose response of a few plant taxa to acute gamma radiation

International Nuclear Information System (INIS)

George, J.T.; Patel, B.B.; Pius, J.; Narula, B.; Shankhadarwar, S.; Rane, V.A.; Venu-Babu, P.; Eapen, S.; Singhal, R.K.

2014-01-01

Micronuclei induction serves as an essential biomarker of radiation stress in a living system, and the simplicity of its detection technique has made it a widely used indicator of radiation damage. The present study was conducted to reveal the cytological dose-response of a few plant taxa, viz., Allium cepa var. aggregatum Linn., Allium sativum Linn., Chlorophytum comosum (Thunb.) Jacques and Eichhornia crassipes (Mart.) Solms, to low LET gamma radiation with special emphasis on the pattern of micronuclei induced across low and high dose regimes. A tri-phasic non-linear dose-response pattern was observed in the four taxa studied, characterized by a low dose linear segment, a plateau and a high dose linear segment. Despite a similar response trend, the critical doses where the phase transitions occurred varied amongst the plant taxa, giving an indication to their relative radiosensitivities. E. crassipes and A. sativum, with their lower critical doses for slope modifications of phase transitions, were concluded as being more radiosensitive as compared to C. comosum and A. cepa, which had relatively higher critical doses. (author)

Cancer risks from ingestion of radiostrontium

Energy Technology Data Exchange (ETDEWEB)

Raabe, O. G.

2004-07-01

Studies have been conducted of the lifetime effects in 403 beagles of the skeletal uptake in seven logarithmically increasing dosage groups of ingested Sr-90. The Sr-90 was fed during skeletal developmental from mid-gestation to adulthood at age 540 days resulting in lifetime protracted beta radiation exposure of the skeleton and some adjacent tissues. Statistical analysis of all types of cancer deaths in the 403 exposed beagles and in 162 unexposed controls indicated that deaths caused by five types of cancer were significantly elevated by high level exposure to Sr-90; these were (1) myeloid leukemia, (2) bone sarcoma, (3) squamous cell carcinoma of periodontal origin, (4) nasal carcinoma, and (5) oral carcinoma. Dose response analysis of these radiation-induced cancer deaths showed non-linear relationships with marked thresholds. A mean lifetime skeletal absorbed dose of 22.5 +/-5.7 Gy SD (22.5 +/-5.7 Sv SD) was associated with the lowest dosage group in which any radiation induced cancer deaths were observed. Three-dimensional models of the observed dose-rate/time/response relationships were fir with maximum likelihood regression methods to describe the risks of death associated with the different types of radiation-induced cancer. The models show that a life-time virtual threshold for cancer risk occurs because the time required to induce cancer is longer at lower radiation dose rates and may exceed the natural life span. Scaling these results to predict human cancer risks from ingestion of Sr-90 shows negligible risks for people whose lifetime cumulative skeletal dose is less than 10 Sv. (Author)

Relationship between attenuation coefficients and dose-spread kernels

International Nuclear Information System (INIS)

Boyer, A.L.

1988-01-01

Dose-spread kernels can be used to calculate the dose distribution in a photon beam by convolving the kernel with the primary fluence distribution. The theoretical relationships between various types and components of dose-spread kernels relative to photon attenuation coefficients are explored. These relations can be valuable as checks on the conservation of energy by dose-spread kernels calculated by analytic or Monte Carlo methods

Conformal irradiation of the prostate: estimating long-term rectal bleeding risk using dose-volume histograms

International Nuclear Information System (INIS)

Hartford, Alan C.; Niemierko, Andrzej; Adams, Judith A.; Urie, Marcia M.; Shipley, William U.

1996-01-01

Purpose: Dose-volume histograms (DVHs) may be very useful tools for estimating probability of normal tissue complications (NTCP), but there is not yet an agreed upon method for their analysis. This study introduces a statistical method of aggregating and analyzing primary data from DVHs and associated outcomes. It explores the dose-volume relationship for NTCP of the rectum, using long-term data on rectal wall bleeding following prostatic irradiation. Methods and Materials: Previously published data were reviewed and updated on 41 patients with Stages T3 and T4 prostatic carcinoma treated with photons followed by perineal proton boost, including dose-volume histograms (DVHs) of each patient's anterior rectal wall and data on the occurrence of postirradiation rectal bleeding (minimum FU > 4 years). Logistic regression was used to test whether some individual combination of dose and volume irradiated might best separate the DVHs into categories of high or low risk for rectal bleeding. Further analysis explored whether a group of such dose-volume combinations might be superior in predicting complication risk. These results were compared with results of the 'critical volume model', a mathematical model based on assumptions of underlying radiobiological interactions. Results: Ten of the 128 tested dose-volume combinations proved to be 'statistically significant combinations' (SSCs) distinguishing between bleeders (14 out of 41) and nonbleeders (27 out of 41), ranging contiguously between 60 CGE (Cobalt Gray Equivalent) to 70% of the anterior rectal wall and 75 CGE to 30%. Calculated odds ratios for each SSC were not significantly different across the individual SSCs; however, analysis combining SSCs allowed segregation of DVHs into three risk groups: low, moderate, and high. Estimates of probabilities of normal tissue complications (NTCPs) based on these risk groups correlated strongly with observed data (p = 0.003) and with biomathematical model-generated NTCPs

Contamination and cancers: low-dose risks and standards of radioprotection

International Nuclear Information System (INIS)

Vignes, S.

1980-01-01

Irradiation of the population due to the running of nuclear power stations represents less than 1% of the natural radioactivity today, and should amount to 3% at most by the year 2 000. The main effects of ionizing radiations are reviewed and their undetectability below 100 rems is underlined. Thus the evaluation of low-dose risks can only be speculative and the cautions hypothesis adopted is that of a linear relationship between dose and effect, together with the absence of threshold. According to calculations the worker, supposedly exposed to 500 mrem a year between ages 18 and 65, would run a 22.2% instead of the normal 22% risk of dying of cancer. As for the population, the risk would increase by only 1 per 10 000 in the year 2 000. This means that no other mutagenic and carcinogenic agent is as well regulated as radioactive pollution and efforts directed at a better control of harmful chemicals, for instance, are only taking an example from the ruling on radioprotection [fr

A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer

International Nuclear Information System (INIS)

Joosten, A; Bochud, F; Moeckli, R

2014-01-01

The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable

Some hybrid models applicable to dose-response relationships

International Nuclear Information System (INIS)

Kumazawa, Shigeru

1992-01-01

A new type of models of dose-response relationships has been studied as an initial stage to explore a reliable extrapolation of the relationships decided by high dose data to the range of low dose covered by radiation protection. The approach is to use a 'hybrid scale' of linear and logarithmic scales; the first model is that the normalized surviving fraction (ρ S > 0) in a hybrid scale decreases linearly with dose in a linear scale, and the second is that the induction in a log scale increases linearly with the normalized dose (τ D > 0) in a hybrid scale. The hybrid scale may reflect an overall effectiveness of a complex system against adverse events caused by various agents. Some data of leukemia in the atomic bomb survivors and of rodent experiments were used to show the applicability of hybrid scale models. The results proved that proposed models fit these data not less than the popular linear-quadratic models, providing the possible interpretation of shapes of dose-response curves, e.g. shouldered survival curves varied by recovery time. (author)

Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

International Nuclear Information System (INIS)

Dijk, Irma W.E.M. van; Cardous-Ubbink, Mathilde C.; Pal, Helena J.H. van der; Heinen, Richard C.; Leeuwen, Flora E. van; Oldenburger, Foppe; Os, Rob M. van; Ronckers, Cécile M.; Schouten–van Meeteren, Antoinette Y.N.; Caron, Huib N.; Koning, Caro C.E.; Kremer, Leontien C.M.

2013-01-01

Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD 2 ). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD 2 in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD 2 , we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD 2 instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience

Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

Energy Technology Data Exchange (ETDEWEB)

Dijk, Irma W.E.M. van, E-mail: i.w.vandijk@amc.uva.nl [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Cardous-Ubbink, Mathilde C. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Pal, Helena J.H. van der [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Heinen, Richard C. [Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Leeuwen, Flora E. van [Department of Epidemiology, Netherlands Cancer Institute, Amsterdam (Netherlands); Oldenburger, Foppe; Os, Rob M. van [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Ronckers, Cécile M. [Dutch Childhood Oncology Group, Long-term Effects after Childhood Cancer, The Hague (Netherlands); Schouten–van Meeteren, Antoinette Y.N. [Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Caron, Huib N. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Koning, Caro C.E. [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Kremer, Leontien C.M. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands)

2013-03-01

Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD{sub 2}). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 years after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD{sub 2} in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD{sub 2}, we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD{sub 2} instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.

Low Dose Risk, Decisions, and Risk Communication

International Nuclear Information System (INIS)

Flynn, James

2002-01-01

The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation

Modified Exponential (MOE) Models: statistical Models for Risk Estimation of Low dose Rate Radiation

International Nuclear Information System (INIS)

Ogata, H.; Furukawa, C.; Kawakami, Y.; Magae, J.

2004-01-01

Simultaneous inclusion of dose and dose-rate is required to evaluate the risk of long term irradiation at low dose-rates, since biological responses to radiation are complex processes that depend both on irradiation time and total dose. Consequently, it is necessary to consider a model including cumulative dose,dose-rate and irradiation time to estimate quantitative dose-response relationship on the biological response to radiation. In this study, we measured micronucleus formation and (3H) thymidine uptake in U2OS, human osteosarcoma cell line, as indicators of biological response to gamma radiation. Cells were exposed to gamma ray in irradiation room bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and propidium iodide. The number of binuclear cells bearing a micronucleus was counted under a florescence microscope. For proliferation inhibition, cells were cultured for 48 h after the irradiation and (3h) thymidine was pulsed for 4h before harvesting. We statistically analyzed the data for quantitative evaluation of radiation risk at low dose/dose-rate. (Author)

The relationship between crude oil spot and futures prices: Cointegration, linear and nonlinear causality

International Nuclear Information System (INIS)

Bekiros, Stelios D.; Diks, Cees G.H.

2008-01-01

The present study investigates the linear and nonlinear causal linkages between daily spot and futures prices for maturities of one, two, three and four months of West Texas Intermediate (WTI) crude oil. The data cover two periods October 1991-October 1999 and November 1999-October 2007, with the latter being significantly more turbulent. Apart from the conventional linear Granger test we apply a new nonparametric test for nonlinear causality by Diks and Panchenko after controlling for cointegration. In addition to the traditional pairwise analysis, we test for causality while correcting for the effects of the other variables. To check if any of the observed causality is strictly nonlinear in nature, we also examine the nonlinear causal relationships of VECM filtered residuals. Finally, we investigate the hypothesis of nonlinear non-causality after controlling for conditional heteroskedasticity in the data using a GARCH-BEKK model. Whilst the linear causal relationships disappear after VECM cointegration filtering, nonlinear causal linkages in some cases persist even after GARCH filtering in both periods. This indicates that spot and futures returns may exhibit asymmetric GARCH effects and/or statistically significant higher order conditional moments. Moreover, the results imply that if nonlinear effects are accounted for, neither market leads or lags the other consistently, videlicet the pattern of leads and lags changes over time. (author)

We can do better than effective dose for estimating or comparing low-dose radiation risks

International Nuclear Information System (INIS)

Brenner, D.J.

2012-01-01

The effective dose concept was designed to compare the generic risks of exposure to different radiation fields. More commonly these days, it is used to estimate or compare radiation-induced cancer risks. For various reasons, effective dose represents flawed science: for instance, the tissue-specific weighting factors used to calculate effective dose are a subjective mix of different endpoints; and the marked and differing age and gender dependencies for different health detriment endpoints are not taken into account. This paper suggests that effective dose could be replaced with a new quantity, ‘effective risk’, which, like effective dose, is a weighted sum of equivalent doses to different tissues. Unlike effective dose, where the tissue-dependent weighting factors are a set of generic, subjective committee-defined numbers, the weighting factors for effective risk are simply evaluated tissue-specific lifetime cancer risks per unit equivalent dose. Effective risk, which has the potential to be age and gender specific if desired, would perform the same comparative role as effective dose, be just as easy to estimate, be less prone to misuse, be more directly understandable, and would be based on solid science. An added major advantage is that it gives the users some feel for the actual numerical values of the radiation risks they are trying to control.

The risk of childhood cancer from low doses of ionizing radiation received in utero

International Nuclear Information System (INIS)

Wakeford, R.; Doll, R.; Bithell, J.F.

1997-01-01

Radiological protection is based upon the assumption that any additional exposure to ionising radiation leads to an increased risk of stochastic adverse health effects. The validity of this assumption is supported by the epidemiological association between childhood cancer and X-ray exposure of the fetus in utero for diagnostic purposes. Evidence for a direct causal interpretation of this association is compelling: the association has high statistical significance, it is consistent across many case-control studies carried out worldwide, and an appropriate dose-response relationship is indicated. Evidence against bias and confounding as alternative explanations is strong. Nonetheless, objections to causality have been raised. Four grounds for controversy are examined in detail, with the conclusion that they do not provide persuasive evidence against a cause and effect relationship. We conclude that acute doses of the order of 10 mGy received by the fetus in utero cause a subsequent increase in the risk of cancer in childhood, and that, in these circumstances, the excess absolute risk coefficient for childhood cancer incidence is 6-12% per Gy. (author)

The relationships between radiation doses and their effects

International Nuclear Information System (INIS)

Beau, P.G.; Nenot, J.C.

1982-01-01

Dose-effect relationships have been developed both for the biological effects studied by Radiobiology and the long-term pathological effects (malignant diseases) studied by Radiation Protection. The former approach chiefly considers the primary biological injuries at the cellular level, and the relationship between the dependent variable characteristic of the effect and the dose -an independent variable- has an explanatory meaning. The parameters associated to the independent variable have a biophysical signification and fit into a model of the action of ionizing radiations. In the latter approach, the relationship is pragmatic and the previous parameters are just the results of a curve-fitting procedure realized on experimental or human data. The biophysical models have led to a general formulation associating a linear term to a quadratic term both of them weighted by an exponential term describing cellular killing at the highest doses. To a certain extent the curves obtained for leukemias, bronchopulmonary and breast cancers prove the validity of the pragmatic model [fr

Radiation doses and risks from internal emitters

International Nuclear Information System (INIS)

Harrison, John; Day, Philip

2008-01-01

This review updates material prepared for the UK Government Committee Examining Radiation Risks from Internal Emitters (CERRIE) and also refers to the new recommendations of the International Commission on Radiological Protection (ICRP) and other recent developments. Two conclusions from CERRIE were that ICRP should clarify and elaborate its advice on the use of its dose quantities, equivalent and effective dose, and that more attention should be paid to uncertainties in dose and risk estimates and their implications. The new ICRP recommendations provide explanations of the calculation and intended purpose of the protection quantities, but further advice on their use would be helpful. The new recommendations refer to the importance of understanding uncertainties in estimates of dose and risk, although methods for doing this are not suggested. Dose coefficients (Sv per Bq intake) for the inhalation or ingestion of radionuclides are published as reference values without uncertainty. The primary purpose of equivalent and effective dose is to enable the summation of doses from different radionuclides and from external sources for comparison with dose limits, constraints and reference levels that relate to stochastic risks of whole-body radiation exposure. Doses are calculated using defined biokinetic and dosimetric models, including reference anatomical data for the organs and tissues of the human body. Radiation weighting factors are used to adjust for the different effectiveness of different radiation types, per unit absorbed dose (Gy), in causing stochastic effects at low doses and dose rates. Tissue weighting factors are used to take account of the contribution of individual organs and tissues to overall detriment from cancer and hereditary effects, providing a simple set of rounded values chosen on the basis of age- and sex-averaged values of relative detriment. While the definition of absorbed dose has the scientific rigour required of a basic physical quantity

Dose response relationship in anti-stress gene regulatory networks.

Science.gov (United States)

Zhang, Qiang; Andersen, Melvin E

2007-03-02

To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products) in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear) depends on changes in the specific values of local response coefficients (gains) distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear, and depending on

Dose response relationship in anti-stress gene regulatory networks.

Directory of Open Access Journals (Sweden)

Qiang Zhang

2007-03-01

Full Text Available To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear depends on changes in the specific values of local response coefficients (gains distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear

Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response

Directory of Open Access Journals (Sweden)

Hemantkumar Chavan

2017-01-01

Full Text Available Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.

Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

Energy Technology Data Exchange (ETDEWEB)

Kleinerman, Ruth A., E-mail: kleinerr@mail.nih.gov [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, Maryland (United States); Smith, Susan A. [Department of Radiation Physics, University of Texas M D Anderson Cancer Center, Houston, Texas (United States); Holowaty, Eric [Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario (Canada); Hall, Per [Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm (Sweden); Pukkala, Eero [Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki (Finland); Vaalavirta, Leila [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Stovall, Marilyn; Weathers, Rita [Department of Radiation Physics, University of Texas M D Anderson Cancer Center, Houston, Texas (United States); Gilbert, Ethel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, Maryland (United States); Aleman, Berthe M.P. [Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam (Netherlands); Kaijser, Magnus [Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Andersson, Michael [Department of Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Storm, Hans [Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen (Denmark); Joensuu, Heikki [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Lynch, Charles F. [Department of Epidemiology, University of Iowa, Iowa City, Iowa (United States); and others

2013-08-01

Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P{sub trend}=.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P{sub trend}=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P{sub trend}=.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer.

Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

International Nuclear Information System (INIS)

Kleinerman, Ruth A.; Smith, Susan A.; Holowaty, Eric; Hall, Per; Pukkala, Eero; Vaalavirta, Leila; Stovall, Marilyn; Weathers, Rita; Gilbert, Ethel; Aleman, Berthe M.P.; Kaijser, Magnus; Andersson, Michael; Storm, Hans; Joensuu, Heikki; Lynch, Charles F.

2013-01-01

Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P trend =.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P trend =.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P trend =.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer

Under which climate and soil conditions the plant productivity-precipitation relationship is linear or nonlinear?

Science.gov (United States)

Ye, Jian-Sheng; Pei, Jiu-Ying; Fang, Chao

2018-03-01

Understanding under which climate and soil conditions the plant productivity-precipitation relationship is linear or nonlinear is useful for accurately predicting the response of ecosystem function to global environmental change. Using long-term (2000-2016) net primary productivity (NPP)-precipitation datasets derived from satellite observations, we identify >5600pixels in the North Hemisphere landmass that fit either linear or nonlinear temporal NPP-precipitation relationships. Differences in climate (precipitation, radiation, ratio of actual to potential evapotranspiration, temperature) and soil factors (nitrogen, phosphorous, organic carbon, field capacity) between the linear and nonlinear types are evaluated. Our analysis shows that both linear and nonlinear types exhibit similar interannual precipitation variabilities and occurrences of extreme precipitation. Permutational multivariate analysis of variance suggests that linear and nonlinear types differ significantly regarding to radiation, ratio of actual to potential evapotranspiration, and soil factors. The nonlinear type possesses lower radiation and/or less soil nutrients than the linear type, thereby suggesting that nonlinear type features higher degree of limitation from resources other than precipitation. This study suggests several factors limiting the responses of plant productivity to changes in precipitation, thus causing nonlinear NPP-precipitation pattern. Precipitation manipulation and modeling experiments should combine with changes in other climate and soil factors to better predict the response of plant productivity under future climate. Copyright © 2017 Elsevier B.V. All rights reserved.

Some aspects of time-dose relationships

International Nuclear Information System (INIS)

Sugawara, Tadashi; Koito, Kazumitsu; Aihara, Toshinori

1985-01-01

One hundred thirty-seven patients with non-small cell lung cancers, 57 with oral cavity cancers and 98 with postoperative breast cancers treated with external radiotherapy from 1974 to 1980 were analyzed to determine optimal trends of time-dose relationships. Superiorities of fractionation factors were examined by comparing the relative local recurrence or expire rates among the subgroups prognostically homogenized in each entities of the diseases. Faborable fractionation factors for the former two diseases were those in which treatment was given in shortened over-all times, and frequently with low fraction dose to the considerably high daily dose. These results indicate the superiority of accelerated fractionation regime to conventional one in the treatment of those diseases. In contrast, any optimal trend was not found with postoperative breast cancers but total dose administered more than 43 Gy. (author)

Exchange Rate – Relative Price Nonlinear Cointegration Relationship in Malaysia

OpenAIRE

Venus Khim-Sen Liew; Chee-Keong Choong; Evan Lau; Kian-Ping Lim

2005-01-01

The finding of exchange rate–relative price nonlinear cointegration relationship in Malaysia, among others, suggests that nonlinear Purchasing Power Parity (PPP) equilibrium may be regarded as reference point in judging the short run misalignment of the Ringgit currency and thereby deducing effective policy actions. Moreover, economists who wish to extend the simple PPP exchange rate model into the more complicated monetary exchange models may do so comfortably, at least in the text of Mala...

A recalculation of the dose-effect-relationship of the ''life span study'' of Hiroshima and Nagasaki with the ''single-hit model''

International Nuclear Information System (INIS)

Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

1996-01-01

The basis of this new model is the multistage process of carcinogeneses. The Single-Hit Model is a further development of the Armitage-Doll Model [1] for the special case of a short exposure. It provides simultaneously the age-dependent mortality-rate (incidence-rate) of the spontaneous and radiation induced solid tumors and dose-effect relationships at any age after exposure. The model results in a biologically based dose-effect relationship, which is similar to the Relativ-Risk-Model suggested by the ICRP 60 [2]. The present model is able to describe the increased mortality rate of the bomb survivors more accurate than the Relativ-Risk-Model. (orig.) [de

Dose response relationship and Alara

International Nuclear Information System (INIS)

Hubert, P.

1986-09-01

In this paper, it will be shown how dose-response relationships allow to give quantitative figures for the detriment of irradiation. At this stage, the detriment is expressed directly as a certain number of health effects, whose valuation is not dealt with here. The present tools for quantifying, their weaknesses and their strenghts, and their scientific basis will be developed

Dose-response relationship for elective neck irradiation of head and neck cancer - facts and controversies

International Nuclear Information System (INIS)

Suwinski, R.; Maciejewski, B.; Withers, H.R.

1998-01-01

The aim of this study is to assign dose-response relationship for subclinical neck metastases of squamous cell head and neck cancer based on extensive survey of 24 data sets collected from the literature. Neck relapse rates (NRR) without and after elective (ENI) or preoperative irradiation were estimated for each site and stage of primary tumor and the reduction in neck relapse rate was calculated. An average NRR without ENI was 22% (12-35% ) and only 2.5% (0-1 0%) after the ENI with total dose of 46- 50 Gy which gives high reduction rate in the risk of neck recurrences being on the average 89% and 42% (0-46%) after preoperative irradiation using 22-30 Gy. Dose response curve for elective and preoperative irradiation have shown that 50 Gy in 2 Gy fraction reduces the incidence of neck relapses in the NO patients by more than 90% and only by less than 50% after total doses lower than 30 Gy. No correlation between the risk of neck metastases without ENI and the reduction in neck relapses after ENI was found. (authors)

Food Groups and Risk of Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Science.gov (United States)

Schwingshackl, Lukas; Schwedhelm, Carolina; Hoffmann, Georg; Knüppel, Sven; Iqbal, Khalid; Andriolo, Violetta; Bechthold, Angela; Schlesinger, Sabrina; Boeing, Heiner

2017-11-01

The aim of this systematic review and meta-analysis was to summarize the evidence on the relation of the intakes of 12 major food groups, including whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages (SSBs) with the risk of hypertension. PubMed, Scopus, and Web of Science were searched systematically until June 2017 for prospective studies having quantitatively investigated the above-mentioned foods. We conducted meta-analysis on the highest compared with the lowest intake categories and linear and nonlinear dose-response meta-analyses to analyze the association. Summary RRs and 95% CIs were estimated by using a random-effects model. Overall, 28 reports were included in the meta-analysis. An inverse association for the risk of hypertension was observed for 30 g whole grains/d (RR: 0.92; 95% CI: 0.87, 0.98), 100 g fruits/d (RR: 0.97; 95% CI: 0.96, 0.99), 28 g nuts/d (RR: 0.70; 95% CI: 0.45, 1.08), and 200 g dairy/d (RR: 0.95; 95% CI: 0.94, 0.97), whereas a positive association for 100 g red meat/d (RR: 1.14; 95% CI: 1.02, 1.28), 50 g processed meat/d (RR: 1.12; 95% CI: 1.00, 1.26), and 250 mL SSB/d (RR: 1.07; 95% CI: 1.04, 1.10) was seen in the linear dose-response meta-analysis. Indication for nonlinear relations of the intakes of whole grains, fruits, fish, and processed meats with the risk of hypertension was detected. In summary, this comprehensive dose-response meta-analysis of 28 reports identified optimal intakes of whole grains, fruits, nuts, legumes, dairy, red and processed meats, and SSBs related to the risk of hypertension. These findings need to be seen under the light of very-low to low quality of meta-evidence. However, the findings support the current dietary guidelines in the prevention of hypertension. © 2017 American Society for Nutrition.

Fruits and vegetables consumption and risk of stroke: a meta-analysis of prospective cohort studies.

Science.gov (United States)

Hu, Dan; Huang, Junqian; Wang, Yuchun; Zhang, Dongfeng; Qu, Yan

2014-06-01

We conducted a meta-analysis to summarize evidence from prospective cohort studies about the association of fruits and vegetables consumption with the risk of stroke. Pertinent studies were identified by a search of Embase and PubMed databases to January 2014. Study-specific relative risks with 95% confidence intervals were pooled using a random-effects model. Dose-response relationship was assessed by restricted cubic spline. Twenty prospective cohort studies were included, involving 16 981 stroke events among 760 629 participants. The multivariable relative risk (95% confidence intervals) of stroke for the highest versus lowest category of total fruits and vegetables consumption was 0.79 (0.75-0.84), and the effect was 0.77 (0.71-0.84) for fruits consumption and 0.86 (0.79-0.93) for vegetables consumption. Subgroup and meta-regression showed that the inverse association of total fruits and vegetables consumption with the risk of stroke was consistent in subgroup analysis. Citrus fruits, apples/pears, and leafy vegetables might contribute to the protection. The linear dose-response relationship showed that the risk of stroke decreased by 32% (0.68 [0.56-0.82]) and 11% (0.89 [0.81-0.98]) for every 200 g per day increment in fruits consumption (P for nonlinearity=0.77) and vegetables consumption (P for nonlinearity=0.62), respectively. Fruits and vegetables consumption are inversely associated with the risk of stroke. © 2014 American Heart Association, Inc.

Dose-response relationship of octylphenol and radiation evaluated by tradescantia-micronucleus assay

International Nuclear Information System (INIS)

Kim, J. K.; Cheon, K. J.; Lee, B. H.; Shin, H. S.; Lee, J. H.

2002-01-01

Many kinds of synthetic chemicals have been being used for various purposes. Some of them are called 'Endocrine Disruptor's because they can disturb the endocrine system of organisms. Presently no technique is established for the quantitative assessment of biological risk of the environmental hormones. The pollen mother cells (PMC) of Tradescantia are very sensitive to chemical toxicants or ionizing radiation, and thus can be used as a biological end-point assessing their effect. Micronucleus frequencies in PMC showed a good dose- and concentration-response relationship for radiation, bisphenol A and octylphenol. A parallel series of experiment using five increasing doses of gamma-ray at 10, 20, 30, 40 and 50 cGy was conducted. The MCN frequencies of 12.0, 25.2, 41.7, 76 and 83 MCN/100 tetrads were observed from each of the increasing gamma-ray dosage groups, respectively. Lenear regression analysis of the gamma-ray data MCN frequencies yielded a correlation coefficient of 0.95. the MCN frequencies in pollen mother cells treated with bisphenol a and octylphenol showed dose-response relationship in a concentration of 0, 1, 2, 4 μM and 0, 4, 10, 20 μM. the MCN frequency for the bisphenol a and octylphenol group yields 2.33, 8.06, 12.7 and 19.6 MCN/100 tetrads for the bisphenol a and 2.33, 2.33, 11.47, 17.6 MCN/100 tetrads for the octylphenol. The MCN frequency of the control was 2.33 MCN/100 tetrads. It is known from the result that Trad-MCN assay can be an excellent tool for detection of biological risk due to environmental toxicants or synthetic chemicals

Optimal dose-response relationships in voice therapy.

Science.gov (United States)

Roy, Nelson

2012-10-01

Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal dose-response relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible "overdosing".

Comprehensive drought characteristics analysis based on a nonlinear multivariate drought index

Science.gov (United States)

Yang, Jie; Chang, Jianxia; Wang, Yimin; Li, Yunyun; Hu, Hui; Chen, Yutong; Huang, Qiang; Yao, Jun

2018-02-01

It is vital to identify drought events and to evaluate multivariate drought characteristics based on a composite drought index for better drought risk assessment and sustainable development of water resources. However, most composite drought indices are constructed by the linear combination, principal component analysis and entropy weight method assuming a linear relationship among different drought indices. In this study, the multidimensional copulas function was applied to construct a nonlinear multivariate drought index (NMDI) to solve the complicated and nonlinear relationship due to its dependence structure and flexibility. The NMDI was constructed by combining meteorological, hydrological, and agricultural variables (precipitation, runoff, and soil moisture) to better reflect the multivariate variables simultaneously. Based on the constructed NMDI and runs theory, drought events for a particular area regarding three drought characteristics: duration, peak, and severity were identified. Finally, multivariate drought risk was analyzed as a tool for providing reliable support in drought decision-making. The results indicate that: (1) multidimensional copulas can effectively solve the complicated and nonlinear relationship among multivariate variables; (2) compared with single and other composite drought indices, the NMDI is slightly more sensitive in capturing recorded drought events; and (3) drought risk shows a spatial variation; out of the five partitions studied, the Jing River Basin as well as the upstream and midstream of the Wei River Basin are characterized by a higher multivariate drought risk. In general, multidimensional copulas provides a reliable way to solve the nonlinear relationship when constructing a comprehensive drought index and evaluating multivariate drought characteristics.

Structure/property relationships in non-linear optical materials

Energy Technology Data Exchange (ETDEWEB)

Cole, J M [Institut Max von Laue - Paul Langevin (ILL), 38 - Grenoble (France); [Durham Univ. (United Kingdom); Howard, J A.K. [Durham Univ. (United Kingdom); McIntyre, G J [Institut Max von Laue - Paul Langevin (ILL), 38 - Grenoble (France)

1997-04-01

The application of neutrons to the study of structure/property relationships in organic non-linear optical materials (NLOs) is described. In particular, charge-transfer effects and intermolecular interactions are investigated. Charge-transfer effects are studied by charge-density analysis and an example of one such investigation is given. The study of intermolecular interactions concentrates on the effects of hydrogen-bonding and an example is given of two structurally similar molecules with very disparate NLO properties, as a result of different types of hydrogen-bonding. (author). 3 refs.

Time and dose in carcinogenesis

International Nuclear Information System (INIS)

Mayneord, W.V.; Clarke, R.H.

1978-05-01

Previous work on the implications of different forms of dose response relationships is extended to include time as a variable, not only in time of irradiation but also in the time of appearance of effects following irradiation. The forms of relationships for time distribution of tumours revealed experimentally for both radiation and chemical carcinogens are first considered. It appears that much data may be correlated in terms of a log-normal distribution of tumour yield following the insult. Further, it is noted, that there is evidence that the median time of tumour appearance may be a function of total dose received or even of dose rate for protracted exposure. Using numerical values of these parameters derived from the biological literature speculative studies have been made of the effects on dose response relationships of using a time distribution of tumour yield, considering both uniform irradiation and point sources. In addition the effects of using dose rate rather than dose to define the log-normal distribution to tumour appearance have been investigated. It is assumed that biological response is directly proportional to dose but that effect is distributed in time. From this linear assumption the appearance of non-linear dose response relationships and apparent thresholds are continually seen. Finally, both the importance of attempting analyses of biological data in terms of stochastic concepts and the need for biological data to test our hypotheses is emphasised. (author)

Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner.

Science.gov (United States)

Tsai, Ming-Ju; Yang, Chih-Jen; Kung, Ya-Ting; Sheu, Chau-Chyun; Shen, Yu-Ting; Chang, Pi-Yu; Huang, Ming-Shyan; Chiu, Herng-Chia

2014-11-01

Higher risk of lung cancer has been noted in patients with type 2 diabetes mellitus (DM). Some observational studies have shown a reduced risk of lung cancer in DM patients taking metformin, but a dose-response relationship has never been reported. The aim of this study is to exam the association between the dose of metformin and the incidence of lung cancer in a Chinese population. The dataset used for this nationwide population-based study is a cohort of 1 million subjects randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. We enrolled all subjects with newly diagnosed type 2 DM between 1997 and 2007. Subjects with a diagnosis of neoplasm before DM diagnosis, those using metformin before DM diagnosis, those with polycystic ovary syndrome, and those with a DM diagnosis before their 15 years of age were excluded. The demographic data and duration, cumulative dose and intensity of metformin use were compared between patients developing lung cancer and those without lung cancer. Totally, 47,356 subjects were identified. After adjusting for age, gender, and modified Charlson Comorbidity Index score, the utilization of metformin was an independent protecting factor, and the risk of developing lung cancer decreased progressively with either the higher cumulative dose or the higher intensity of metformin use. This study revealed that the use of metformin decreased the risk of lung cancer in a dose-dependent manner in patients with type 2 DM. The chemo-preventive effect of metformin deserves further study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Volume dose of organs at risk in the irradiated volume

International Nuclear Information System (INIS)

Hishikawa, Yoshio; Tanaka, Shinichi; Miura, Takashi

1984-01-01

Absorbed dose of organs at risk in the 50% irradiated volume needs to be carefully monitored because there is high risk of radiation injury. This paper reports on the histogram of threedimensional volume dose of organs at risk, which is obtained by computer calculation of CT scans. In order to obtain this histogram, CT is first performed in the irradiation field. The dose in each pixel is then examined by the computer as to each slice. After the pixels of all slices in the organ at risk of the irradiated field are classified according to the doses, the number of pixels in the same dose class is counted. The result is expressed in a histogram. The histogram can show the differences of influence to organs at risk given by various radiation treatment techniques. Total volume dose of organs at risk after radiotherapy can also be obtained by integration of each dose of different treatment techniques. (author)

A meta-analysis including dose-response relationship between night shift work and the risk of colorectal cancer.

Science.gov (United States)

Wang, Xiao; Ji, Alin; Zhu, Yi; Liang, Zhen; Wu, Jian; Li, Shiqi; Meng, Shuai; Zheng, Xiangyi; Xie, Liping

2015-09-22

A meta-analysis was conducted to quantitatively evaluate the correlation between night shift work and the risk of colorectal cancer. We searched for publications up to March 2015 using PubMed, Web of Science, Cochrane Library, EMBASE and the Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles and relevant reviews were also checked. OR and 95% CI were used to assess the degree of the correlation between night shift work and risk of colorectal cancer via fixed- or random-effect models. A dose-response meta-analysis was performed as well. The pooled OR estimates of the included studies illustrated that night shift work was correlated with an increased risk of colorectal cancer (OR = 1.318, 95% CI 1.121-1.551). No evidence of publication bias was detected. In the dose-response analysis, the rate of colorectal cancer increased by 11% for every 5 years increased in night shift work (OR = 1.11, 95% CI 1.03-1.20). In conclusion, this meta-analysis indicated that night shift work was associated with an increased risk of colorectal cancer. Further researches should be conducted to confirm our findings and clarify the potential biological mechanisms.

Multidisciplinary European Low Dose Initiative (MELODI). Strategic research agenda for low dose radiation risk research

Energy Technology Data Exchange (ETDEWEB)

Kreuzer, M. [Federal Office for Radiation Protection, BfS, Department of Radiation Protection and Health, Neuherberg (Germany); Auvinen, A. [University of Tampere, Tampere (Finland); STUK, Helsinki (Finland); Cardis, E. [ISGlobal, Barcelona Institute for Global Health, Barcelona (Spain); Durante, M. [Institute for Fundamental Physics and Applications, TIFPA, Trento (Italy); Harms-Ringdahl, M. [Stockholm University, Centre for Radiation Protection Research, Stockholm (Sweden); Jourdain, J.R. [Institute for Radiological Protection and Nuclear Safety, IRSN, Fontenay-aux-roses (France); Madas, B.G. [MTA Centre for Energy Research, Environmental Physics Department, Budapest (Hungary); Ottolenghi, A. [University of Pavia, Physics Department, Pavia (Italy); Pazzaglia, S. [Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Rome (Italy); Prise, K.M. [Queens University Belfast, Belfast (United Kingdom); Quintens, R. [Belgian Nuclear Research Centre, SCK-CEN, Mol (Belgium); Sabatier, L. [French Atomic Energy Commission, CEA, Paris (France); Bouffler, S. [Public Health England, PHE, Chilton (United Kingdom)

2018-03-15

MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html). (orig.)

Radiological dose reconstruction for birds reconciles outcomes of Fukushima with knowledge of dose-effect relationships

International Nuclear Information System (INIS)

Garnier-Laplace, Jacqueline; Beaugelin-Seiller, Karine; Della-Vedova, Claire; Metivier, Jean-Michel; Ritz, Christian; Mousseau, Timothy A.; Pape Moeller, Anders

2015-01-01

We reconstructed the radiological dose for birds observed at 300 census sites in the 50-km northwest area affected by the accident at the Fukushima Daiichi nuclear power plant over 2011-2014. Substituting the ambient dose rate measured at the census points (from 0.16 to 31 μGy h -1 ) with the dose rate reconstructed for adult birds of each species (from 0.3 to 97 μGy h -1 ), we confirmed that the overall bird abundance at Fukushima decreased with increasing total doses. This relationship was directly consistent with exposure levels found in the literature to induce physiological disturbances in birds. Among the 57 species constituting the observed bird community, we found that 90% were likely chronically exposed at a dose rate that could potentially affect their reproductive success. We quantified a loss of 22.6% of the total number of individuals per increment of one unit log10-transformed total dose (in Gy), over the four-year post-accident period in the explored area. We estimated that a total dose of 0.55 Gy reduced by 50% the total number of birds in the study area over 2011-2014. The data also suggest a significant positive relationship between total dose and species diversity. (authors)

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer

DEFF Research Database (Denmark)

Jakobsen, Anders; Ploen, John; Vuong, Té

2012-01-01

PURPOSE: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation...

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

Science.gov (United States)

Rørvik, Eivind; Thörnqvist, Sara; Stokkevåg, Camilla H; Dahle, Tordis J; Fjaera, Lars Fredrik; Ytre-Hauge, Kristian S

2017-06-01

The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LET d ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LET d based models for a simulated spread out Bragg peak (SOBP) scenario. The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were

Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies.

Science.gov (United States)

Schwingshackl, Lukas; Hoffmann, Georg; Lampousi, Anna-Maria; Knüppel, Sven; Iqbal, Khalid; Schwedhelm, Carolina; Bechthold, Angela; Schlesinger, Sabrina; Boeing, Heiner

2017-05-01

The aim of this systematic review and meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups and risk of type 2 diabetes (T2D). We conducted a systematic search in PubMed, Embase, Medline (Ovid), Cochrane Central, and Google Scholar for prospective studies investigating the association between whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages (SSB) on risk of T2D. Summary relative risks were estimated using a random effects model by contrasting categories, and for linear and non-linear dose-response relationships. Six out of the 12 food-groups showed a significant relation with risk of T2D, three of them a decrease of risk with increasing consumption (whole grains, fruits, and dairy), and three an increase of risk with increasing consumption (red meat, processed meat, and SSB) in the linear dose-response meta-analysis. There was evidence of a non-linear relationship between fruits, vegetables, processed meat, whole grains, and SSB and T2D risk. Optimal consumption of risk-decreasing foods resulted in a 42% reduction, and consumption of risk-increasing foods was associated with a threefold T2D risk, compared to non-consumption. The meta-evidence was graded "low" for legumes and nuts; "moderate" for refined grains, vegetables, fruit, eggs, dairy, and fish; and "high" for processed meat, red meat, whole grains, and SSB. Among the investigated food groups, selecting specific optimal intakes can lead to a considerable change in risk of T2D.

Dose-response relationships and threshold levels in skin and respiratory allergy

NARCIS (Netherlands)

Arts, J.H.E.; Mommers, C.; Heer, C.de

2006-01-01

A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well

Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

NARCIS (Netherlands)

Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university

The dose-response relationship between in-ear occupational noise exposure and hearing loss.

Science.gov (United States)

Rabinowitz, Peter M; Galusha, Deron; Dixon-Ernst, Christine; Clougherty, Jane E; Neitzel, Richard L

2013-10-01

Current understanding of the dose-response relationship between occupational noise and hearing loss is based on cross-sectional studies prior to the widespread use of hearing protection, and with limited data regarding noise exposures below 85 dBA. We report on the hearing loss experience of a unique cohort of industrial workers, with daily monitoring of noise inside of hearing protection devices. At an industrial facility, workers exhibiting accelerated hearing loss were enrolled in a mandatory programme to monitor daily noise exposures inside of hearing protection. We compared these noise measurements (as time-weighted LAVG) to interval rates of high-frequency hearing loss over a 6-year period using a mixed-effects model, adjusting for potential confounders. Workers' high-frequency hearing levels at study inception averaged more than 40 dB Hearing threshold level (HTL). Most noise exposures were less than 85 dBA (mean LAVG 76 dBA, IQR 74-80 dBA). We found no statistical relationship between LAvg and high-frequency hearing loss (p=0.53). Using a metric for monthly maximum noise exposure did not improve model fit. At-ear noise exposures below 85 dBA did not show an association with risk of high-frequency hearing loss among workers with substantial past noise exposure and hearing loss at baseline. Therefore, effective noise control to below 85 dBA may lead to significant reduction in occupational hearing loss risk in such individuals. Further research is needed on the dose-response relationship of noise and hearing loss in individuals with normal hearing and little prior noise exposure.

Dose-response relationship of leukemia incidence among atomic bomb survivors and their controls by absorbed marrow dose and two types of leukemia Hiroshima and Nagasaki, October 1950 - December 1978

International Nuclear Information System (INIS)

Ishimaru, Toranosuke; Otake, Masanori; Ichimaru, Michito; Mikami, Motoko.

1982-07-01

Analysis of the relationship of the incidence of leukemia to gamma and neutron dose among atomic bomb survivors until 1971 has been reported previously by RERF. The present inquiry was prompted by the extension of case finding to 1978 and by the recent availability of new dose estimates for this fixed cohort. It is focused on the relationship of absorbed marrow dose of gamma rays and neutrons to the incidence of two types of leukemia in the fixed cohort of A-bomb survivors and their controls, the Life Span Study extended sample, in the period October 1950-December 1978. Three dose-response models have been fitted to the data on acute leukemia and chronic granulocytic leukemia. The relationship of the incidence of acute leukemia to gamma and neutron dose again suggests that the ''best'' fitting model involves a dependence on the square of the gamma dose and a linear dependence on neutrons. The estimated relative biological effectiveness (RBE) of neutrons in the induction of acute leukemia is approximately 44/√Dn(Dn = neutron dose) under this model. Based on the 95% confidence limits of the estimated RBE, the risk of this disease is estimated as 0.0026 - 0.0072 cases per million person-years per rem 2 of marrow dose. This analysis has failed, however, to produce a significant dose-response function for the incidence of chronic granulocytic leukemia in relation to the two kinds of radiation. (author)

The Relationship between Nonconservative Schemes and Initial Values of Nonlinear Evolution Equations

Institute of Scientific and Technical Information of China (English)

林万涛

2004-01-01

For the nonconservative schemes of the nonlinear evolution equations, taking the one-dimensional shallow water wave equation as an example, the necessary conditions of computational stability are given.Based on numerical tests, the relationship between the nonlinear computational stability and the construction of difference schemes, as well as the form of initial values, is further discussed. It is proved through both theoretical analysis and numerical tests that if the construction of difference schemes is definite, the computational stability of nonconservative schemes is decided by the form of initial values.

Non-linear failure analysis of HCPB blanket for DEMO taking into account high dose irradiation

Energy Technology Data Exchange (ETDEWEB)

Aktaa, J., E-mail: jarir.aktaa@kit.edu [Karlsruhe Institute of Technology (KIT), Institute for Applied Materials, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany); Kecskés, S.; Pereslavtsev, P.; Fischer, U.; Boccaccini, L.V. [Karlsruhe Institute of Technology (KIT), Institute for Neutron Physics and Reactor Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen (Germany)

2014-10-15

Highlights: • First non-linear structural analysis for the European Helium Cooled Pebble Bed Blanket Module taking into account high dose irradiation. • Most critical areas were identified and analyzed with regard to the effect of irradiation on predicted damage at these areas. • Despite the extensive computing time 100 cycles were simulated by using the sub-modelling technique investigating damage at most critical area. • The results show a positive effect of irradiation on calculated damage which is mainly attributed to the irradiation induced hardening. - Abstract: For the European helium cooled pebble bed (HCPB) blanket of DEMO the reduced activation ferritic martensitic steel EUROFER has been selected as structural material. During operation the HCPB blanket will be subjected to complex thermo-mechanical loadings and high irradiation doses. Taking into account the material and structural behaviour under these conditions is a precondition for a reliable blanket design. For considering high dose irradiation in structural analysis of the DEMO blanket, the coupled deformation damage model, extended recently taking into account the influence of high dose irradiation on the material behaviour of EUROFER and implemented in the finite element code ABAQUS, has been used. Non-linear finite element (FE) simulations of the DEMO HCPB blanket have been performed considering the design of the HCPB Test Blanket Module (TBM) as reference and the thermal and mechanical boundary conditions of previous analyses. The irradiation dose rate required at each position in the structure as an additional loading parameter is estimated by extrapolating the results available for the TBM in ITER scaling the value calculated in neutronics and activation analysis for ITER boundary conditions to the DEMO boundary conditions. The results of the FE simulations are evaluated considering damage at most critical highly loaded areas of the structure and discussed with regard to the impact of

Non-linear failure analysis of HCPB blanket for DEMO taking into account high dose irradiation

International Nuclear Information System (INIS)

Aktaa, J.; Kecskés, S.; Pereslavtsev, P.; Fischer, U.; Boccaccini, L.V.

2014-01-01

Highlights: • First non-linear structural analysis for the European Helium Cooled Pebble Bed Blanket Module taking into account high dose irradiation. • Most critical areas were identified and analyzed with regard to the effect of irradiation on predicted damage at these areas. • Despite the extensive computing time 100 cycles were simulated by using the sub-modelling technique investigating damage at most critical area. • The results show a positive effect of irradiation on calculated damage which is mainly attributed to the irradiation induced hardening. - Abstract: For the European helium cooled pebble bed (HCPB) blanket of DEMO the reduced activation ferritic martensitic steel EUROFER has been selected as structural material. During operation the HCPB blanket will be subjected to complex thermo-mechanical loadings and high irradiation doses. Taking into account the material and structural behaviour under these conditions is a precondition for a reliable blanket design. For considering high dose irradiation in structural analysis of the DEMO blanket, the coupled deformation damage model, extended recently taking into account the influence of high dose irradiation on the material behaviour of EUROFER and implemented in the finite element code ABAQUS, has been used. Non-linear finite element (FE) simulations of the DEMO HCPB blanket have been performed considering the design of the HCPB Test Blanket Module (TBM) as reference and the thermal and mechanical boundary conditions of previous analyses. The irradiation dose rate required at each position in the structure as an additional loading parameter is estimated by extrapolating the results available for the TBM in ITER scaling the value calculated in neutronics and activation analysis for ITER boundary conditions to the DEMO boundary conditions. The results of the FE simulations are evaluated considering damage at most critical highly loaded areas of the structure and discussed with regard to the impact of

Dose-response relationships for environmentally mediated infectious disease transmission models.

Directory of Open Access Journals (Sweden)

Andrew F Brouwer

2017-04-01

Full Text Available Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose-response relationship. Much of the work characterizing the functional forms of dose-response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose-response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i middle- and high-dose data do not constrain the low-dose response, and different dose-response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain.

Radiation dose and cancer risk to children undergoing skull radiography

International Nuclear Information System (INIS)

Mazonakis, Michael; Damilakis, John; Raissaki, Maria; Gourtsoyiannis, Nicholas

2004-01-01

Background: Limited data exist in the literature concerning the patient-effective dose from paediatric skull radiography. No information has been provided regarding organ doses, patient dose during PA skull projection, risk of cancer induction and dose to comforters, i.e. individuals supporting children during exposure. Objective: To estimate patient-effective dose, organ doses, lifetime cancer mortality risk to children and radiation dose to comforters associated with skull radiography. Materials and methods: Data were collected from 136 paediatric examinations, including AP, PA and lateral skull radiographs. Entrance-surface dose (ESD) and dose to comforters were measured using thermoluminescent dosimeters. Patients were divided into the following age groups: 0.5-2, 3-7, 8-12 and 13-18 years. The patient-effective dose and corresponding organ doses were calculated using data from the NRPB and Monte Carlo techniques. The risk for fatal cancer induction was assessed using appropriate risk coefficients. Results: For AP, PA and lateral skull radiography, effective dose ranges were 8.8-25.4, 8.2-27.3 and 8.4-22.7 μSv respectively, depending upon the age of the child. For each skull projection, the organs receiving doses above 10 μGy are presented. The number of fatal cancers was found to be less than or equal to 2 per 1 million children undergoing a skull radiograph. The mean radiation dose absorbed by the hands of comforters was 13.4 μGy. Conclusions: The current study provides detailed tabular and graphical data on ESD, effective dose, organ doses and lifetime cancer mortality risk to children associated with AP, PA and lateral skull projections at all patient ages. (orig.)

Nonparametric estimation of benchmark doses in environmental risk assessment

Science.gov (United States)

Piegorsch, Walter W.; Xiong, Hui; Bhattacharya, Rabi N.; Lin, Lizhen

2013-01-01

Summary An important statistical objective in environmental risk analysis is estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a pre-specified benchmark response in a dose-response experiment. In such settings, representations of the risk are traditionally based on a parametric dose-response model. It is a well-known concern, however, that if the chosen parametric form is misspecified, inaccurate and possibly unsafe low-dose inferences can result. We apply a nonparametric approach for calculating benchmark doses, based on an isotonic regression method for dose-response estimation with quantal-response data (Bhattacharya and Kong, 2007). We determine the large-sample properties of the estimator, develop bootstrap-based confidence limits on the BMDs, and explore the confidence limits’ small-sample properties via a short simulation study. An example from cancer risk assessment illustrates the calculations. PMID:23914133

Multiple myeloma among atomic bomb survivors in Hiroshima and Nagasaki, 1950-76: relationship to radiation dose absorbed by marrow

International Nuclear Information System (INIS)

Ichimaru, M.; Ishimaru, T.; Mikami, M.; Matsunaga, M.

1982-01-01

The relationship between atomic bomb exposure and the incidence of multiple myeloma has been examined in a fixed cohort of atomic bomb survivors and controls in the life-span study sample for Hiroshima and Nagasaki. From October 1950 to December 1976, 29 cases of multiple myeloma were confirmed in this sample. Our analysis shows that the standardized relative risk (RR) adjusted for city, sex, and age at the time of bombings (ATB) increased with marrow-absorbed radiation dose. The increased RR does not appear to differ between cities or sexes and is demonstrable only for those survivors whose age ATB was between 20 and 59 years. The estimated risk in these individuals is approximately 0.48 cases/million person-years/rad for bone marrow total dose. This excess risk did not become apparent in individuals receiving 50 rad or more in marrow total dose until 20 years or more after exposure

Correlation between ultrasonic nonlinearity and elastic nonlinearity in heat-treated aluminum alloy

Energy Technology Data Exchange (ETDEWEB)

Kim, Jong Beom; Jhang, Kyung Young [Hanyang University, Seoul (Korea, Republic of)

2017-04-15

The nonlinear ultrasonic technique is a potential nondestructive method to evaluate material degradation, in which the ultrasonic nonlinearity parameter is usually measured. The ultrasonic nonlinearity parameter is defined by the elastic nonlinearity coefficients of the nonlinear Hooke’s equation. Therefore, even though the ultrasonic nonlinearity parameter is not equal to the elastic nonlinearity parameter, they have a close relationship. However, there has been no experimental verification of the relationship between the ultrasonic and elastic nonlinearity parameters. In this study, the relationship is experimentally verified for a heat-treated aluminum alloy. Specimens of the aluminum alloy were heat-treated at 300°C for different periods of time (0, 1, 2, 5, 10, 20, and 50 h). The relative ultrasonic nonlinearity parameter of each specimen was then measured, and the elastic nonlinearity parameter was determined by fitting the stress-strain curve obtained from a tensile test to the 5th-order-polynomial nonlinear Hooke’s equation. The results showed that the variations in these parameters were in good agreement with each other.

Effective dose and cancer risk in PET/CT exams

International Nuclear Information System (INIS)

Pinto, Gabriella M.; Sa, Lidia Vasconcellos de

2013-01-01

Due to the use of radiopharmaceutical positron-emitting in PET exam and realization of tomography by x-ray transmission in CT examination, an increase of dose with hybrid PET/CT technology is expected. However, differences of doses have been reported in many countries for the same type of procedure. It is expected that the dose is an influent parameter to standardize the protocols of PET/CT. This study aimed to estimate the effective doses and absorbed in 65 patients submitted to oncological Protocol in a nuclear medicine clinic in Rio de Janeiro, considering the risk of induction of cancer from the scan. The CT exam-related doses were estimated with a simulator of PMMA and simulated on the lmPACT resistance, which for program effective dose, were considered the weight factors of the lCRP 103. The PET exam doses were estimated by multiplying the activity administered to the patient with the ICRP dose 80 factors. The radiological risk for cancer incidence were estimated according to the ICRP 103. The results showed that the effective dose from CT exam is responsible for 70% of the effective total in a PET/CT scan. values of effective dose for the PET/CT exam reached average values of up to 25 mSv leading to a risk of 2, 57 x 10 -4 . Considering that in staging of oncological diseases at least four tests are performed annually, the total risk comes to 1,03x 10 -3

The Dose Response Relationship between In Ear Occupational Noise Exposure and Hearing Loss

Science.gov (United States)

Rabinowitz, Peter M.; Galusha, Deron; Dixon-Ernst, Christine; Clougherty, Jane E.; Neitzel, Richard L.

2014-01-01

Objectives Current understanding of the dose-response relationship between occupational noise and hearing loss is based on cross-sectional studies prior to the widespread use hearing protection and with limited data regarding noise exposures below 85dBA. We report on the hearing loss experience of a unique cohort of industrial workers with daily monitoring of noise inside of hearing protection devices. Methods At an industrial facility, workers exhibiting accelerated hearing loss were enrolled in a mandatory program to monitor daily noise exposures inside of hearing protection. We compared these noise measurements (as time-weighted LAVG) to interval rates of high frequency hearing loss over a six year period using a mixed effects model, adjusting for potential confounders. Results Workers’ high frequency hearing levels at study inception averaged more than 40 dB hearing threshold level (HTL). Most noise exposures were less than 85dBA (mean LAVG 76 dBA, interquartile range 74 to 80 dBA). We found no statistical relationship between LAvg and high frequency hearing loss (p = 0.53). Using a metric for monthly maximum noise exposure did not improve model fit. Conclusion At-ear noise exposures below 85dBA did not show an association with risk of high frequency hearing loss among workers with substantial past noise exposure and hearing loss at baseline. Therefore, effective noise control to below 85dBA may lead to significant reduction in occupational hearing loss risk in such individuals. Further research is needed on the dose response relationship of noise and hearing loss in individuals with normal hearing and little prior noise exposure. PMID:23825197

On the linearity of the dose-effect relationship of DNA double strand breaks

International Nuclear Information System (INIS)

Chadwick, K.H.; Leenhouts, H.P.

1994-01-01

Most radiation biologists believe that DNA double-strand breaks are induced linearly with radiation dose for all types of radiation. Since 1985, with the advent of elution and gel electrophoresis techniques which permit the measurement of DNA double-strand breaks induced in mammalian cells at doses having radiobiological relevance, the true nature of the dose-effect relationship has been brought into some doubt. Many investigators measured curvilinear dose-effect relationships and a few found good correlations between the induction of the DNA double-strand breaks and cell survival. We approach the problem pragmatically by assuming that the induction of DNA double-strand breaks by 125 I Auger electron emitters incorporated into the DNA of the cells is a linear function of the number of 125 I decays, and by comparing the dose-effect relationship for sparsely ionizing radiation against this standard. The conclusion drawn that the curvilinear dose-effect relationships and the correlations with survival are real. (Author)

Is the investment-uncertainty relationship nonlinear? An empirical analysis for the Netherlands

NARCIS (Netherlands)

Bo, H; Lensin, R

We examine the investment-uncertainty relationship for a panel of Dutch non-financial firms. The system generalized method of moments (GMM) estimates suggest that the effect of uncertainty on investment is nonlinear: for low levels of uncertainty an increase in uncertainty has a positive effect on

Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

Science.gov (United States)

Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

2017-10-01

Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy -1 ) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used

Study of the dose-effect relationship of γ-H2AX radiation

International Nuclear Information System (INIS)

Cui Shuangshuang; Fan Yaguang; Gun Zhijuan; Wang Jixian; Zhao Yongcheng; Sun Yuping

2010-01-01

Objective: By using laser scanning confocal microscopy (LSCM) to test the dose-effects relationship between ionizing radiation intensity and quantity of the γ-H2AX in vivo and in vitro respectively, and the consistency relationship between the vivo and vitro retrial. Methods: To irradiate the peripheral blood from Wister female rats by 137 Cs at 7 with different doses (0, 0.5, 1, 2, 2.54, 4, 6, 8 Gy) extract the lymphocytes from the peripheral blood and detect the dose-effects relationship between irradiation intensity and number of γ-H2AX foci. Results: There are good dose-effects relationships between the irradiation and foci number both in vivo and in vitro, which are linear, Y vivo =0.096+0.13X; Y vitro =0.040+0.21X. And there is good consistency (R=0.98) between the γ-H2AX in vivo and in vitro. Conclusions: γ-H2AX has the possibility for clinical trial as an indicator, and we can use vitro trials in place of the vivo trails to evaluate the dose people received. (authors)

Mathematical model for evaluation of dose-rate effect on biological responses to low dose γ-radiation

International Nuclear Information System (INIS)

Ogata, H.; Kawakami, Y.; Magae, J.

2003-01-01

Full text: To evaluate quantitative dose-response relationship on the biological response to radiation, it is necessary to consider a model including cumulative dose, dose-rate and irradiation time. In this study, we measured micronucleus formation and [ 3 H] thymidine uptake in human cells as indices of biological response to gamma radiation, and analyzed mathematically and statistically the data for quantitative evaluation of radiation risk at low dose/low dose-rate. Effective dose (ED x ) was mathematically estimated by fitting a general function of logistic model to the dose-response relationship. Assuming that biological response depends on not only cumulative dose but also dose-rate and irradiation time, a multiple logistic function was applied to express the relationship of the three variables. Moreover, to estimate the effect of radiation at very low dose, we proposed a modified exponential model. From the results of fitting curves to the inhibition of [ 3 H] thymidine uptake and micronucleus formation, it was obvious that ED 50 in proportion of inhibition of [ 3 H] thymidine uptake increased with longer irradiation time. As for the micronuclei, ED 30 also increased with longer irradiation times. These results suggest that the biological response depends on not only total dose but also irradiation time. The estimated response surface using the three variables showed that the biological response declined sharply when the dose-rate was less than 0.01 Gy/h. These results suggest that the response does not depend on total cumulative dose at very low dose-rates. Further, to investigate the effect of dose-rate within a wider range, we analyzed the relationship between ED x and dose-rate. Fitted curves indicated that ED x increased sharply when dose-rate was less than 10 -2 Gy/h. The increase of ED x signifies the decline of the response or the risk and suggests that the risk approaches to 0 at infinitely low dose-rate

Radiation tolerance of the cervical spinal cord: incidence and dose-volume relationship of symptomatic and asymptomatic late effects following high dose irradiation of paraspinal tumors

International Nuclear Information System (INIS)

Liu, Mitchell C.C.; Munzenrider, John E.; Finkelstein, Dianne; Liebsch, Norbert; Adams, Judy; Hug, Eugen B.

1997-01-01

changes was between 2 and 8.5 months after radiation therapy. Two risk factors appeared to have significant impact when all incidences were considered: proton portion of tumor dose > 55 CGE (p=.023), and spinal cord surface dose ≥ 60 CGE (p=.045). For patients receiving 55 CGE to >1.5cc of spinal cord, the risk of developing imaging changes was significantly higher (p=.0074). Age < 40 years was found to be correlated with higher incidence of Lhermitt's syndrome (p=.002). No variable was significant for predicting incidence of sensory or motor deficits. Conclusions: For chordomas and chondrosarcomas of the cervical spine, requiring high radiation doses, the guidelines of limiting maximum spinal cord surface dose to ≤ 64 CGE and maximum spinal cord center dose to ≤ 53 CGE appears safe. For the patients who had been treated within the above tolerance dose, none of them had developed motor deficits. Both a significant dose response relationship as well as volume effect for symptomatic or asymptomatic spinal cord changes were observed. The incidence of 1 patient, who developed motor damage after higher radiation doses to the spinal cord than generally allowed, emphasizes the importance of strict guidelines for critical, normal tissues in high dose, conformal radiation treatment

Patient-specific radiation dose and cancer risk for pediatric chest CT.

Science.gov (United States)

Li, Xiang; Samei, Ehsan; Segars, W Paul; Sturgeon, Gregory M; Colsher, James G; Frush, Donald P

2011-06-01

To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0-16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDI(vol)) or dose-length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Organ dose normalized by tube current-time product or CTDI(vol) decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current-time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current-time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (chest CT protocols. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1. RSNA, 2011

Physical requirements for measurement of radiation dose and their relationship to personnel dose meter design and use

International Nuclear Information System (INIS)

Chabot, G.E. Jr.; Jimenez, M.A.; Skrable, K.W.

1978-01-01

This paper stems from the concerns of the authors with both the design of current personnel dose meters and the interpretation of dose information from them in light of the actual physical requirements to measure dose. These concerns have been reinforced and extended following a comparative study of the responses of particular TLD and film systems and as the result of a recent national survey on personnel dosimetry conducted by the authors. Among the major points discussed are the systems available for penetrating and shallow dose assessment, dose meter calibration, the measurement and interpretation of skin dose, and the deficiencies of neutron albedo dose meters for routine personnel use. Calibration considerations address the questions of whether or not a phantom should be used and the difference in interpretation of responses with and without a phantom; the relationship between calculated and measured doses; and electronic equilibrium considerations in the measurement of photon doses. Matters of importance in relation to skin dose measurement include techniques in use to interpret skin dose from dose meter response; the appropriateness of evaluation of the surface dose to the live skin layer versus the average dose to the live skin layer and the limitations and requirements on dose meter design with respect to the dose being evaluated; and the significance of dose meter response in relationship to currently used beta calibration standards. Regarding the use of TLD albedo type neutron dose meters currently available, considerations are extended to the strong energy spectral dependence of the dose meter response and the possibility of making significant over or underestimations of neutron dose equivalent, depending on the calibration techniques used and the spectral quality encountered. (author)

[Relationship between shift work and overweight/obesity in male steel workers].

Science.gov (United States)

Xiao, M Y; Wang, Z Y; Fan, H M; Che, C L; Lu, Y; Cong, L X; Gao, X J; Liu, Y J; Yuan, J X; Li, X M; Hu, B; Chen, Y P

2016-11-10

Objective: To investigate the relationship between shift work and overweight/obesity in male steel workers. Methods: A questionnaire survey was conducted among the male steel workers selected during health examination in Tangshan Steel Company from March 2015 to March 2016. The relationship between shift work and overweight/obesity in the male steel workers were analyzed by using logistic regression model and restricted cubic splinemodel. Results: A total of 7 262 male steel workers were surveyed, the overall prevalence of overweight/obesitywas 64.5% (4 686/7 262), the overweight rate was 34.3% and the obesity rate was 30.2%, respectively. After adjusting for age, educational level and average family income level per month by multivariable logistic regression analysis, shift work was associated with overweight/obesity and obesity in the male steel workers. The OR was 1.19(95% CI : 1.05-1.35) and 1.15(95% CI : 1.00-1.32). Restricted cubic spline model analysis showed that the relationship between shift work years and overweight/obesity in the male steel workers was a nonlinear dose response one (nonlinear test χ 2 =7.43, P shift work years and obesity in the male steel workers was a nonlinear dose response one (nonlinear test χ 2 =10.48, P Shift work was associated with overweight and obesity in the male steel workers, and shift work years and overweight/obesity had a nonlinear relationship.

Non-linear character of dose dependences of chromosome aberration frequency in radiation-damaged root

International Nuclear Information System (INIS)

Kravets, E.A.; Berezhnaya, V.V.; Sakada, V.I.; Rashidov, N.M.; Grodzinskij, D.M.; Kravets, E.A.; Berezhnaya, V.V.; Sakada, V.I.; Rashidov, N.M.; Grodzinskij, D.M.

2012-01-01

The dose dependences of the aberrant anaphases in the root meristem in 48 hours after the irradiation have non-linear character and a plateau in the region about 6-8 Gy. The plateau indicates the activation of recovery processes. In the plateau range, the level of damages for this genotype is 33% for aberrant anaphases (FAA), 2.3 aberrations per aberrant anaphase (A/AC), and 0.74 aberrations for the total number of anaphases. At 10 Gy, the dose curve forms the exponential region caused by the involvement of the large number of new cells with unrepaired damages in the mutation process. The increase of A/AC to 1.1 indicate the ''criticality'' of the meristem radiation damage.

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

Science.gov (United States)

2009-01-01

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

Nonlinear mixed effects dose response modeling in high throughput drug screens: application to melanoma cell line analysis.

Science.gov (United States)

Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren; Yin, Hongwei; Hendricks, William P D; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar; LoRusso, Patricia M; Vuori, Kristiina; Trent, Jeffrey M; Schork, Nicholas J

2018-01-12

Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC 50 ). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations. We consider the application of two methods, each rooted in nonlinear mixed effects (NLME) models, that test the relationship relationships between estimated cell line DRCs and factors that might mitigate response. Both methods leverage estimation and testing techniques that consider the simultaneous analysis of different cell lines to draw inferences about any one cell line. One of the methods is designed to provide an omnibus test of the differences between cell line DRCs that is not focused on any one aspect of the DRC (such as the IC 50 value). We simulated different settings and compared the different methods on the simulated data. We also compared the proposed methods against traditional IC 50 -based methods using 40 melanoma cell lines whose transcriptomes, proteomes, and, importantly, BRAF and related mutation profiles were available. Ultimately, we find that the NLME-based methods are more robust, powerful and, for the omnibus test, more flexible, than traditional methods. Their application to the melanoma cell lines reveals insights into factors that may be clinically useful.

Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?

International Nuclear Information System (INIS)

Little, M.P.

2010-01-01

In this paper we review the evidence for departure from linearity for malignant and non-malignant disease and in the light of this assess likely mechanisms, and in particular the potential role for non-targeted effects. Excess cancer risks observed in the Japanese atomic bomb survivors and in many medically and occupationally exposed groups exposed at low or moderate doses are generally statistically compatible. For most cancer sites the dose-response in these groups is compatible with linearity over the range observed. The available data on biological mechanisms do not provide general support for the idea of a low dose threshold or hormesis. This large body of evidence does not suggest, indeed is not statistically compatible with, any very large threshold in dose for cancer, or with possible hormetic effects, and there is little evidence of the sorts of non-linearity in response implied by non-DNA-targeted effects. There are also excess risks of various types of non-malignant disease in the Japanese atomic bomb survivors and in other groups. In particular, elevated risks of cardiovascular disease, respiratory disease and digestive disease are observed in the A-bomb data. In contrast with cancer, there is much less consistency in the patterns of risk between the various exposed groups; for example, radiation-associated respiratory and digestive diseases have not been seen in these other (non-A-bomb) groups. Cardiovascular risks have been seen in many exposed populations, particularly in medically exposed groups, but in contrast with cancer there is much less consistency in risk between studies: risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well known (but unobserved) risk factors. In the absence of a convincing mechanistic explanation of epidemiological evidence that is, at present, less than persuasive, a cause-and-effect interpretation of the reported

Low dose effects of ionizing radiations in in vitro and in vivo biological systems: a multi-scale approach study

International Nuclear Information System (INIS)

Antoccia, A.; Berardinelli, F.; Argazzi, E.; Balata, M.; Bedogni, R.

2011-01-01

Long-term biological effects of low-dose radiation are little known nowadays and its carcinogenic risk is estimated on the assumption that risk remains linearly proportional to the radiation dose down to low-dose levels. However in the last 20 years this hypothesis has gradually begun to seem in contrast with a huge collection of experimental evidences, which has shown the presence of plethora of non-linear phenomena (including hypersensitivity and induced radioresistance, adaptive response, and non-targeted phenomena like bystander effect and genomic instability) occurring after low-dose irradiation. These phenomena might imply a non-linear behaviour of cancer risk curves in the low-dose region and question the validity of the Linear No-Threshold (LNT) model currently used for cancer risk assessment through extrapolation from existing high-dose data. Moreover only few information is available regarding the effects induced on cryo preserved cells by multi-year background radiation exposure, which might induce a radiation-damage accumulation, due to the inhibition of cellular repair mechanisms. In this framework, the multi-year Excalibur (Exposure effects at low doses of ionizing radiation in biological culture) experiment, funded by INFN-CNS5, has undertaken a multi-scale approach investigation on the biological effects induced in in vitro and in vivo biological systems, in culture and cryo preserved conditions, as a function of radiation quality (X/γ-rays, protons, He-4 ions of various energies) and dose, with particular emphasis on the low-dose region and non-linear phenomena, in terms of different biological endpoints.

Possible factors determining the non-linearity in the VO2-power output relationship in humans: theoretical studies.

Science.gov (United States)

Korzeniewski, Bernard; Zoladz, Jerzy A

2003-08-01

At low power output exercise (below lactate threshold), the oxygen uptake increases linearly with power output, but at high power output exercise (above lactate threshold) some additional oxygen consumption causes a non-linearity in the overall VO(2) (oxygen uptake rate)-power output relationship. The functional significance of this phenomenon for human exercise tolerance is very important, but the mechanisms underlying it remain unknown. In the present work, a computer model of oxidative phosphorylation in intact skeletal muscle developed previously is used to examine the background of this relationship in different modes of exercise. Our simulations demonstrate that the non-linearity in the VO(2)-power output relationship and the difference in the magnitude of this non-linearity between incremental exercise mode and square-wave exercise mode (constant power output exercise) can be generated by introducing into the model some hypothetical factor F (group of associated factors) that accumulate(s) in time during exercise. The performed computer simulations, based on this assumption, give proper time courses of changes in VO(2) and [PCr] after an onset of work of different intensities, including the slow component in VO(2), well matching the experimental results. Moreover, if it is assumed that the exercise terminates because of fatigue when the amount/intensity of F exceed some threshold value, the model allows the generation of a proper shape of the well-known power-duration curve. This fact suggests that the phenomenon of the non-linearity of the VO(2)-power output relationship and the magnitude of this non-linearity in different modes of exercise is determined by some factor(s) responsible for muscle fatigue.

Association between tea consumption and risk of cognitive disorders: A dose-response meta-analysis of observational studies.

Science.gov (United States)

Liu, Xueying; Du, Xiaoyuan; Han, Guanying; Gao, Wenyuan

2017-06-27

The epidemiological evidence for a dose-response relationship between tea consumption and risk of cognitive disorders is sparse. The aim of the study was to summarize the evidence for the association of tea consumption with risk of cognitive disorders and assess the dose-response relationship. We searched electronic databases of Pubmed, Embase, and Cochrane Library (from 1965 to Jan 19, 2017) for eligible studies that published in the international journals. A random-effects model was used to pool the most adjusted odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Seventeen studies involving 48,435 participants were included in our study. The meta-analysis showed that a higher tea consumption was associated with a significant reduction in the risk of cognitive disorders (OR=0.73, 95% CI: 0.65-0.82). When considering the specific types of tea consumption, the significantly inverse association is only found in green tea consumption (OR=0.64, 95% CI: 0.53-0.77) but not in black/oolong tea consumption (OR=0.75, 95% CI: 0.55-1.01). Dose-response meta-analysis indicated that tea consumption is linearly associated with a reduced risk of cognitive disorders. An increment of 100 ml/day, 300 ml/day, and 500 ml/day of tea consumption was associated with a 6% (OR=0.94, 95% CI: 0.92-0.96), 19% (OR=0.81, 95% CI: 0.74-0.88), and 29% (OR=0.71, 95% CI: 0.62-0.82) lower risk of cognitive disorders. Tea consumption is inversely and linearly related to the risk of cognitive disorders. More studies are needed to further confirm our findings.

Assessing dose-response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity.

Science.gov (United States)

Zoeller, R Thomas; Vandenberg, Laura N

2015-05-15

The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose-response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts' knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions.

Forecasting Value-at-Risk Using Nonlinear Regression Quantiles and the Intraday Range

NARCIS (Netherlands)

C.W.S. Chen (Cathy); R. Gerlach (Richard); B.B.K. Hwang (Bruce); M.J. McAleer (Michael)

2011-01-01

textabstractValue-at-Risk (VaR) is commonly used for financial risk measurement. It has recently become even more important, especially during the 2008-09 global financial crisis. We propose some novel nonlinear threshold conditional autoregressive VaR (CAViar) models that incorporate intra-day

A review of in vitro dose-effect relationships

International Nuclear Information System (INIS)

Dolphin, G.W.

1978-01-01

One of the principal reasons for investigating the relationship between absorbed dose and the number of chromosome aberrations per cell in lymphocytes taken from samples of human peripheral blood is to obtain a calibration curve for biological dosimetry. Factors affecting the radiation-induced aberration yield in vitro of T lymphocytes are reviewed under the following heads: temperature, oxygen effect, inter-mitotic death, mitotic delay, dose rate background of aberrations in normal humans, mathematical representation. (U.K.)

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

Energy Technology Data Exchange (ETDEWEB)

Feinendegen, L.E

2003-07-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

International Nuclear Information System (INIS)

Feinendegen, L.E.

2003-01-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

On possible risks of low-dose irradiation

International Nuclear Information System (INIS)

Hug, O.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Neuherberg/Muenchen

1974-01-01

The survey on more recent experimental and epidemiological data and newer concepts for a realistic estimation of the radiation risk leads to the conclusion that for radiation late damages and possibly also for genetic damages with a chronical radiation exposure in the order of magnitude of the natural radiation exposure and probably also in the order of magnitude of the maximum permissible radiation dose, the risk is very probably lower than is to be expected based on the findings after relatively high doses and dose rates. A few less direct comparative studies have detected a time factor of 3 to 5. Considering the analysis of the RBW demely ionizing radiation which at high doses is not greater than 3, increases with decreasing dose and according to biophysical considerations, can possibly reach a value of 30, an effectiveness reduced by a factor of 10 of small doses and dose rates of loosely ionizing radiation would be even to be expected. All radiobiological knowledge on the effect of ionizing radiation allows one to expect that even smallest radiation doses can cause cellular damages due to the linear irreversable components of the radiation effect and probably that these damages can even be the starting point of a malignant tumour. Regarding this cancer-initiating effect however, the effectiveness of loosely ionizing radiation per rad in the region of natural radiation exposure lie considerably below that existing at high doses and dose rates. Whether however this initial carcinogenic effect of very small doses is at all noticeable during the average life duration in an increase of the spontaneous age-specific tumour rate is questionable if the assumption is confirmed that with decreasing dose, the time manifestation of the radiation induced tumours is delayed. (orig./LH) [de

Conceptus radiation dose and risk from chest screen-film radiography

International Nuclear Information System (INIS)

Damilakis, John; Perisinakis, Kostas; Dimovasili, Evangelia; Prassopoulos, Panos; Gourtsoyiannis, Nicholas; Varveris, Haralambos

2003-01-01

The objectives of the present study were to (a) estimate the conceptus radiation dose and risks for pregnant women undergoing posteroanterior and anteroposterior (AP) chest radiographs, (b) study the conceptus dose as a function of chest thickness of the patient undergoing chest radiograph, and (c) investigate the possibility of a conceptus to receive a dose of more than 10 mGy, the level above which specific measurements of conceptus doses may be necessary. Thermoluminescent dosimeters were used for dose measurements in anthropomorphic phantoms simulating pregnancy at the three trimesters of gestation. The effect of chest thickness on conceptus dose and risk was studied by adding slabs of lucite on the anterior and posterior surface of the phantom chest. The conceptus risk for radiation-induced childhood fatal cancer and hereditary effects was calculated based on appropriate risk factors. The average AP chest dimension (d a ) was estimated for 51 women of childbearing age from chest CT examinations. The value of d a was estimated to be 22.3 cm (17.4-27.2 cm). The calculated maximum conceptus dose was 107 x 10 -3 mGy for AP chest radiographs performed during the third trimester of pregnancy with maternal chest thickness of 27.2 cm. This calculation was based on dose data obtained from measurements in the phantoms and d a estimated from the patient group. The corresponding average excess of childhood cancer was 10.7 per million patients. The risk for hereditary effects was 1.1 per million births. Radiation dose for a conceptus increases exponentially as chest thickness increases. The conceptus dose at the third trimester is higher than that of the second and first trimesters. The results of the current study suggest that chest radiographs carried out in women at any time during gestation will result in a negligible increase in risk of radiation-induced harmful effects to the unborn child. After a properly performed maternal chest X-ray, there is no need for

Conceptus radiation dose and risk from chest screen-film radiography.

Science.gov (United States)

Damilakis, John; Perisinakis, Kostas; Prassopoulos, Panos; Dimovasili, Evangelia; Varveris, Haralambos; Gourtsoyiannis, Nicholas

2003-02-01

The objectives of the present study were to (a) estimate the conceptus radiation dose and risks for pregnant women undergoing posteroanterior and anteroposterior (AP) chest radiographs, (b) study the conceptus dose as a function of chest thickness of the patient undergoing chest radiograph, and (c) investigate the possibility of a conceptus to receive a dose of more than 10 mGy, the level above which specific measurements of conceptus doses may be necessary. Thermoluminescent dosimeters were used for dose measurements in anthropomorphic phantoms simulating pregnancy at the three trimesters of gestation. The effect of chest thickness on conceptus dose and risk was studied by adding slabs of lucite on the anterior and posterior surface of the phantom chest. The conceptus risk for radiation-induced childhood fatal cancer and hereditary effects was calculated based on appropriate risk factors. The average AP chest dimension (d(a)) was estimated for 51 women of childbearing age from chest CT examinations. The value of d(a) was estimated to be 22.3 cm (17.4-27.2 cm). The calculated maximum conceptus dose was 107 x 10(-3) mGy for AP chest radiographs performed during the third trimester of pregnancy with maternal chest thickness of 27.2 cm. This calculation was based on dose data obtained from measurements in the phantoms and d(a) estimated from the patient group. The corresponding average excess of childhood cancer was 10.7 per million patients. The risk for hereditary effects was 1.1 per million births. Radiation dose for a conceptus increases exponentially as chest thickness increases. The conceptus dose at the third trimester is higher than that of the second and first trimesters. The results of the current study suggest that chest radiographs carried out in women at any time during gestation will result in a negligible increase in risk of radiation-induced harmful effects to the unborn child. After a properly performed maternal chest X-ray, there is no need for

Conceptus radiation dose and risk from chest screen-film radiography

Energy Technology Data Exchange (ETDEWEB)

Damilakis, John; Perisinakis, Kostas; Dimovasili, Evangelia [Department of Medical Physics, University of Crete, Faculty of Medicine, P.O. Box 1393, 714 09 Iraklion, Crete (Greece); Prassopoulos, Panos; Gourtsoyiannis, Nicholas [Department of Radiology, University of Crete, Faculty of Medicine, P.O. Box 1393, 714 09 Iraklion, Crete (Greece); Varveris, Haralambos [Department of Radiotherapy, University of Crete, Faculty of Medicine, P.O. Box 1393, 714 09 Iraklion, Crete (Greece)

2003-02-01

The objectives of the present study were to (a) estimate the conceptus radiation dose and risks for pregnant women undergoing posteroanterior and anteroposterior (AP) chest radiographs, (b) study the conceptus dose as a function of chest thickness of the patient undergoing chest radiograph, and (c) investigate the possibility of a conceptus to receive a dose of more than 10 mGy, the level above which specific measurements of conceptus doses may be necessary. Thermoluminescent dosimeters were used for dose measurements in anthropomorphic phantoms simulating pregnancy at the three trimesters of gestation. The effect of chest thickness on conceptus dose and risk was studied by adding slabs of lucite on the anterior and posterior surface of the phantom chest. The conceptus risk for radiation-induced childhood fatal cancer and hereditary effects was calculated based on appropriate risk factors. The average AP chest dimension (d{sub a}) was estimated for 51 women of childbearing age from chest CT examinations. The value of d{sub a} was estimated to be 22.3 cm (17.4-27.2 cm). The calculated maximum conceptus dose was 107 x 10{sup -3} mGy for AP chest radiographs performed during the third trimester of pregnancy with maternal chest thickness of 27.2 cm. This calculation was based on dose data obtained from measurements in the phantoms and d{sub a} estimated from the patient group. The corresponding average excess of childhood cancer was 10.7 per million patients. The risk for hereditary effects was 1.1 per million births. Radiation dose for a conceptus increases exponentially as chest thickness increases. The conceptus dose at the third trimester is higher than that of the second and first trimesters. The results of the current study suggest that chest radiographs carried out in women at any time during gestation will result in a negligible increase in risk of radiation-induced harmful effects to the unborn child. After a properly performed maternal chest X-ray, there is

Patient dose and risk in mammography

International Nuclear Information System (INIS)

Law, J.

1991-01-01

Patient dose in mammography is estimated by two methods compared and giving agreement. A mean tissue dose of about 1 mGy per film is found for a breast of 4.5 cm compressed thickness. Variables affecting dose are then considered quantitatively, including compressed breast thickness, tube potential, grids, magnification and beam collimation. The variables having the greatest effect are breast thickness and magnification. The dose estimates are combined with existing data on breast cancer induction to predict the risk of carcinogenesis in a breast screening programme. For example, in a screening centre performing 15 000 examinations per year, only one induced cancer is predicted in about 7 years of screening under average UK conditions of age and breast thickness. (author)

Risk of cancer subsequent to low-dose radiation

International Nuclear Information System (INIS)

Warren, S.

1980-01-01

The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident

Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008

Energy Technology Data Exchange (ETDEWEB)

Moseeva, Maria B.; Azizova, Tamara V.; Grigoryeva, Evgenia S. [Southern Urals Biophysics Institute (SUBI), Ozyorsk, Chelyabinsk Region (Russian Federation); Haylock, Richard [Public Health of England, London (United Kingdom)

2014-05-15

The new Mayak Worker Dosimetry System 2008 (MWDS-2008) was published in 2013 and supersedes the Doses-2005 dosimetry system for Mayak Production Association (PA) workers. It provides revised external and internal dose estimates based on the updated occupational history data. Using MWDS-2008, a cohort of 18,856 workers first employed at one of the main Mayak PA plants during 1948-1972 and followed up to 2005 was identified. Incidence and mortality risks from ischemic heart disease (IHD) (International Classification of Diseases (ICD)-9 codes 410-414) and from cerebrovascular diseases (CVD) (ICD-9 codes 430-438) were examined in this cohort and compared with previously published risk estimates in the same cohort based on the Doses-2005 dosimetry system. Significant associations were observed between doses from external gamma-rays and IHD and CVD incidence and also between internal doses from alpha-radiation and IHD mortality and CVD incidence. The estimates of excess relative risk (ERR)/Gy were consistent with those estimates from the previous studies based on Doses-2005 system apart from the relationship between CVD incidence and internal liver dose where the ERR/Gy based on MWDS-2008 was just over three times higher than the corresponding estimate based on Doses-2005 system. Adjustment for smoking status did not show any effect on the estimates of risk from internal alpha-particle exposure. (orig.)

Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme

International Nuclear Information System (INIS)

Sneed, Penny K.; Lamborn, Kathleen R.; Larson, David A.; Prados, Michael D.; Malec, Mary K.; McDermott, Michael W.; Weaver, Keith A.; Phillips, Theodore L.; Wara, William M.; Gutin, Philip H.

1996-01-01

Purpose: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125 I implant boost after external beam radiotherapy. Methods and Materials: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analyses of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. Results: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm 3 of normal brain. Conclusion: Although higher minimum brachytherapy tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy

Risk of low-doses in radiodiagnosis; Risque des faibles doses en radiodiagnostic. Mythes, reglementation et rationalite

Energy Technology Data Exchange (ETDEWEB)

Cordoliani, Y.S.; Sarrazin, J.L.; Le Frian, G.; Soulie, D.; Leveque, C. [Hopital d`Instruction des Armees du Val-de-Grace, 75 - Paris (France)

1997-12-31

The effect of low doses of X-rays is inferred from the indubitable effects of high doses in human carcinogenesis, Genetic and teratogenic effects are mainly inferred from animal experimentation because clinical surveys of irradiated pregnant women have failed to demonstrate such consequences in the children, except for mental retardation after Japanese atomic bombing. Since no evidence of carcinogenic effect has been produced by epidemiological studies for doses lower than 500 mSv. the estimation of the risk due to low doses has been extrapolated from the linear relation between dose and cancers at high doses. Such an extrapolation gives a maximal risk which is falsely used as a probability of cancer. The actual risk lies between zero and this maximal number, and many epidemiologic surveys in people receiving doses much higher than the mean level of background irradiation failed to demonstrate higher rate of cancer. The explanation of this fact, which is supported by the most recent biological data, is the efficacy of the DNA repair system at low level of exposure to ionizing radiations. We expose the principles of regulation of radioprotection for workers, and give estimations of the doses delivered to the patients and the personnel by diagnostic investigations, by comparing these doses with those of natural irradiation. Practical aspect for conventional and computed radiology are exposed for patients and workers. (authors)

Total Risk Management for Low Dose Radiation Exposures

International Nuclear Information System (INIS)

Simic, Z.; Mikulicic, V.; Sterc, D.

2012-01-01

Our civilization is witnessing about century of nuclear age mixed with enormous promises and cataclysmic threats. Nuclear energy seems to encapsulate both potential for pure good and evil or at least we humans are able to perceive that. These images are continuously with us and they are both helping and distracting from making best of nuclear potentials for civilization. Today with nuclear use significantly present and with huge potential to further improve our life with energy and medical use it is of enormous importance to try to have calmed, rational, and objective view on potential risks and certain benefits. Because all use of nuclear energy proved that their immediate risks are negligible (i.e., Three Mile Island and Fukushima) or much smaller than from the other alternatives (i.e., Chernobyl) it seems that the most important issue is the amount of risk from the long term effects to people from exposure to small doses of radiation. A similar issue is present in the increased use of modern computational tomography and other radiation sources use in medicine for examination and therapy. Finally, extreme natural exposures are third such potential risk sources. Definition of low doses varies depending on the way of delivery (i.e., single, multiple or continuous exposures), and for this paper usual dose of 100 mSv is selected as yearly upper amount. There are three very different scientifically supported views on the potential risks from the low doses exposure. The most conservative theory is that all radiation is harmful, and even small increments from background levels (i.e., 2-3 mSv) present additional risk. This view is called linear no threshold theory (LNT) and it is accepted as a regulatory conservative simple approach which guarantees safety. Risk is derived from the extrapolation of the measured effects of high levels of radiation. Opposite theory to LNT is hormesis which assumes that in fact small doses of radiation are helpful and they are improving our

Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better?

International Nuclear Information System (INIS)

Vicini, Frank A.; Abner, Anthony; Baglan, Kathy L.; Kestin, Larry L.; Martinez, Alvaro A.

2001-01-01

Purpose: Data were reviewed addressing the association between radiation therapy (RT) dose and treatment outcome for localized prostate cancer to help clarify the existence of a potential dose-response relationship. Methods and Materials: Articles were identified through the MEDLINE database, CancerLit database, and reference lists of relevant articles. Studies were categorized into four groups based upon the endpoint analyzed, including biochemical control (BC), local control (LC), pathologic control (PC), and cause-specific survival (CSS). The impact of increasing RT dose with each endpoint was recorded. Results: Twenty-two trials involving a total of 11,297 patients were identified. Of the 11 trials addressing the association of RT dose with LC, 9 showed statistically significant improvements. Of the 12 trials that reported BC with RT dose, all showed statistically significant improvements. Two out of 4 studies analyzing PC with increasing dose showed a positive correlation. Finally, 3 out of 9 studies addressing RT dose with CSS showed statistically significant improvements. Despite inconclusive results, patients with poor risk features (e.g., prostate-specific antigen [PSA] ≥10, Gleason score [GS] ≥7, or tumor stage ≥T2b) were most likely to benefit from increasing dose with respect to each endpoint. However, the optimal RT dose and the magnitude of benefit of dose escalation could not be identified. Conclusions: Although RT dose appears to correlate with various measures of treatment outcome, objective, high-quality data addressing this critical issue are still lacking. At the present time, the absolute improvement in outcome due to dose escalation, the subset of patients benefiting most, and the optimal dose remain to be defined

Re-distribution of brachytherapy dose using a differential dose prescription adapted to risk of local failure in low-risk prostate cancer patients

DEFF Research Database (Denmark)

Rylander, Susanne; Polders, Daniel; Steggerda, Marcel J

2015-01-01

BACKGROUND AND PURPOSE: We investigated the application of a differential target- and dose prescription concept for low-dose-rate prostate brachytherapy (LDR-BT), involving a re-distribution of dose according to risk of local failure and treatment-related morbidity. MATERIAL AND METHODS: Our study......- and dose prescription concept of prescribing a lower dose to the whole gland and an escalated dose to the GTV using LDR-BT seed planning was technically feasible and resulted in a significant dose-reduction to urethra and bladder neck....

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

Directory of Open Access Journals (Sweden)

Dropkin Greg

2009-12-01

Full Text Available Abstract 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

Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer

International Nuclear Information System (INIS)

Pearcey, R.G.; Petereit, D.G.

2000-01-01

This paper investigates the outcome using different dose/fractionation schedules in high dose rate (HDR) post-operative vaginal vault radiotherapy in patients with low to intermediate risk endometrial cancer. The world literature was reviewed and thirteen series were analyzed representing 1800 cases. A total of 12 vaginal vault recurrences were identified representing an overall vaginal control rate of 99.3%. A wide range of dose fractionation schedules and techniques have been reported. In order to analyze a dose response relationship for tumor control and complications, the biologically effective doses to the tumor and late responding tissues were calculated using the linear quadratic model. A threshold was identified for complications, but not vaginal control. While dose fractionation schedules that delivered a biologically effective dose to the late responding tissues in excess of 100 Gy 3 (LQED = 60 Gy) predicted for late complications, dose fractionation schedules that delivered a modest dose to the vaginal surface (50 Gy 10 or LQED = 30 Gy) appeared tumoricidal with vaginal control rates of at least 98%. By using convenient, modest dose fractionation schedules, HDR vaginal vault - brachytherapy yields very high local control and extremely low morbidity rates. (author)

A Multiphase Non-Linear Mixed Effects Model: An Application to Spirometry after Lung Transplantation

Science.gov (United States)

Rajeswaran, Jeevanantham; Blackstone, Eugene H.

2014-01-01

In medical sciences, we often encounter longitudinal temporal relationships that are non-linear in nature. The influence of risk factors may also change across longitudinal follow-up. A system of multiphase non-linear mixed effects model is presented to model temporal patterns of longitudinal continuous measurements, with temporal decomposition to identify the phases and risk factors within each phase. Application of this model is illustrated using spirometry data after lung transplantation using readily available statistical software. This application illustrates the usefulness of our flexible model when dealing with complex non-linear patterns and time varying coefficients. PMID:24919830

New risk estimates at low doses

International Nuclear Information System (INIS)

Fry, R.J.M.

1992-01-01

The age of molecular radiation epidemiology may be at hand. The techniques are available to establish with the degree of precision required to determine whether agent-specific mutations can be identified consistently. A concerted effort to examine radiation-induced changes in as many relevant genes as possible appears to be justified. Cancers in those exposed to low doses of ionizing radiation should be chosen for the investigation. Parallel studies of radiation-induced cancers in experimental animals would not only complement the human studies, but perhaps reveal approaches to extrapolation of risk estimates across species. A caveat should be added to this optimistic view of what molecular studies might contribute to the knotty problem of risk estimates at low doses. The suggestions are made by one with no expertise in the field of molecular biology

Relationships betwen mitotic delay and the dose rate of X radiation

International Nuclear Information System (INIS)

Yi, P.N.; Rha, C.K.; Evans, H.H.; Beer, J.Z.

1994-01-01

Upon exposure of cells to radiation delivered at a continuous low dose rate, cell proliferation may be sustained with the cells exhibiting a constant doubling time that is independent of the total dose. The doubling time or mitotic delay under these conditions has been shown to depend on the dose rate in HeLa, V79 and P388F cells. Reanalysis of the data for these particular cell lines shows that there is a threshold dose rate for mitotic delay, and that above the threshold there is a linear relationship between the length of mitotic delay and the logarithm of the dose rate which is referred to as the dose-rate response. We have observed the same relationships for L5178Y (LY)-R and LY-S cells exposed to low-dose-rate radiation. The threshold dose rates for LY-R, LY-S and P388F cells are similar (0.01-0.02 Gy/h) and are much lower than for V79 and HeLa cells. The slope of the dose-rate response curve is the greatest for HeLa cells, followed in order by LY-S, V79 and P388F cells, and finally by LY-R cells. The slopes for HeLa and LY-R cells differ by a factor of 35. 20 refs., 3 figs., 1 tab

Lysis solution composition and non-linear dose-response to ionizing radiation in the non-denaturing DNA filter elution technique

International Nuclear Information System (INIS)

Radford, I.R.

1990-01-01

The suggestion by Okayasu and Iliakis (1989) that the non-linear dose-response curve, obtained with the non-denaturing filter elution technique for mammalian cells exposed to low-LET radiation, is the result of a technical artefact, was not confirmed. (author)

Dose-stress synergism in cancer risk assessment

International Nuclear Information System (INIS)

Pop-Jordanova, N.; Pop-Jordanov, J.

2001-01-01

Our hypothesis is that the relatively low risk of cancer or leukaemia from depleted uranium, as predicted by the World Health Organization and the International Atomic Energy Agency, is a result of neglecting the synergism between physico-chemical agents and psychological stress agents (here shortly denoted as dose-stress synergism). We use the modified risk assessment model that comprises a psycho-somatic extension, originally developed by us for assessing the risks of energy sources. Our preliminary meta-analysis of animal and human studies on cancers confirmed the existence of stress effects, including the amplifying synergism. Consequently, the psychological stress can increase the probability of even small toxic chemical or ionizing radiation exposure to produce malignancy. Such dose-stress synergism might influence the health risks among military personnel and the residents in the highly stressful environment in the Balkans. Further investigation is needed to estimate the order of magnitude of these combined effects in particular circumstances. (Original)

Patient Doses and Risk Evaluation in Bone Mineral Densitometry

International Nuclear Information System (INIS)

Angelucci, M.; Borio, R.; Chiocchini, S.; Degli Esposti, P.; Dipilato, A.C.; Policani, G.

1999-01-01

The aim of this work was to evaluate the equipment dose to the organs and tissues and the effective dose of patients undergoing the most frequent examinations carried out in bone mineral densitometry (BMD): lumbar spine and femur. Experimental measurements of absorbed doses on a Rando phantom, allow comparison of the performances of three different photon emitter facilities. The comparison of the entrance and exit doses measured on a Rando phantom and on 50 female non-obese patients show that entrance doses on Rando can be used as 'diagnostic reference levels' for patients. A quantitative estimate of the stochastic risk due to BMD procedures was made: the results obtained show that the stochastic risk is very low and that the BMD is, at present, the most confirmed procedure for osteoporosis diagnosis and management. (author)

The Non-Linear Relationship between BMI and Health Care Costs and the Resulting Cost Fraction Attributable to Obesity.

Science.gov (United States)

Laxy, Michael; Stark, Renée; Peters, Annette; Hauner, Hans; Holle, Rolf; Teuner, Christina M

2017-08-30

This study aims to analyse the non-linear relationship between Body Mass Index (BMI) and direct health care costs, and to quantify the resulting cost fraction attributable to obesity in Germany. Five cross-sectional surveys of cohort studies in southern Germany were pooled, resulting in data of 6757 individuals (31-96 years old). Self-reported information on health care utilisation was used to estimate direct health care costs for the year 2011. The relationship between measured BMI and annual costs was analysed using generalised additive models, and the cost fraction attributable to obesity was calculated. We found a non-linear association of BMI and health care costs with a continuously increasing slope for increasing BMI without any clear threshold. Under the consideration of the non-linear BMI-cost relationship, a shift in the BMI distribution so that the BMI of each individual is lowered by one point is associated with a 2.1% reduction of mean direct costs in the population. If obesity was eliminated, and the BMI of all obese individuals were lowered to 29.9 kg/m², this would reduce the mean direct costs by 4.0% in the population. Results show a non-linear relationship between BMI and health care costs, with very high costs for a few individuals with high BMI. This indicates that population-based interventions in combination with selective measures for very obese individuals might be the preferred strategy.

Single point estimation of phenytoin dosing: a reappraisal.

Science.gov (United States)

Koup, J R; Gibaldi, M; Godolphin, W

1981-11-01

A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

Dose-response relationship in local radiotherapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Hee Chul; Seong, Jinsil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Suh, Chang Ok

2002-01-01

Purpose: Dose escalation using three-dimensional conformal radiotherapy (3D-CRT) is based on the hypothesis that increasing the dose can enhance tumor control. This study aimed to determine whether a dose-response relationship exists in local radiotherapy for primary hepatocellular carcinoma (HCC). Methods and Materials: One hundred fifty-eight patients were enrolled in the present study between January 1992 and March 2000. The exclusion criteria included the presence of an extrahepatic metastasis, liver cirrhosis of Child class C, tumors occupying more than two-thirds of the entire liver, and a performance status on the Eastern Cooperative Oncology Group scale of more than 3. Radiotherapy was given to the field, including the tumor, with generous margin using 6- or 10-MV X-rays. The mean radiation dose was 48.2 ± 7.9 Gy in daily 1.8-Gy fractions. The tumor response was assessed based on diagnostic radiologic examinations, including a computed tomography scan, magnetic resonance imaging, and hepatic artery angiography 4-8 weeks after the completion of treatment. Liver toxicity and gastrointestinal complications were evaluated. Results: An objective response was observed in 106 of 158 (67.1%) patients. Statistical analysis revealed that the total dose was the most significant factor associated with the tumor response. The response rates in patients treated with doses 50 Gy were 29.2%, 68.6%, and 77.1%, respectively. Survivals at 1 and 2 years after radiotherapy were 41.8% and 19.9%, respectively, with a median survival time of 10 months. The rate of liver toxicity according to the doses 50 Gy was 4.2%, 5.9%, and 8.4%, respectively, and the rate of gastrointestinal complications was 4.2%, 9.9%, and 13.2%, respectively. Conclusions: The present study showed the existence of a dose-response relationship in local radiotherapy for primary HCC. Only the radiation dose was a significant factor for predicting an objective response. The results of this study showed that 3D

Dose response relationship in local radiotherapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok

2001-01-01

In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2±7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver

Exploring Longitudinal Risk-return Relationships

DEFF Research Database (Denmark)

Andersen, Torben J.; Bettis, Richard A.

2015-01-01

We study a longitudinal fit model of adaptation and its association with the longitudinal risk-return relationship. The model allows the firm to adjust its position in response to partial learning about a changing environment characterized by two path-dependent processes—a random walk and a stoch......We study a longitudinal fit model of adaptation and its association with the longitudinal risk-return relationship. The model allows the firm to adjust its position in response to partial learning about a changing environment characterized by two path-dependent processes—a random walk...... can lead to the inverse longitudinal risk-return relationships observed empirically. We discuss this apparent paradox and the possible resolution between mindless and conscious behavior as plausible causes of the longitudinal Bowman Paradox....

Methods for Addressing Uncertainty and Variability to Characterize Potential Health Risk From Trichloroethylene-Contaminated Ground Water Beale Air Force Base in California: Integration of Uncertainty and Variability in Pharmacokinetics and Dose-Response; TOPICAL

International Nuclear Information System (INIS)

Bogen, K.T.

1999-01-01

Traditional estimates of health risk are typically inflated, particularly if cancer is the dominant endpoint and there is fundamental uncertainty as to mechanism(s) of action. Risk is more realistically characterized if it accounts for joint uncertainty and interindividual variability after applying a unified probabilistic approach to the distributed parameters of all (linear as well as nonlinear) risk-extrapolation models involved. Such an approach was applied to characterize risks to potential future residents posed by trichloroethylene (TCE) in ground water at an inactive landfill site on Beale Air Force Base in California. Variability and uncertainty were addressed in exposure-route-specific estimates of applied dose, in pharmacokinetically based estimates of route-specific metabolized fractions of absorbed TCE, and in corresponding biologically effective doses estimated under a genotoxic/linear (MA(sub g)) vs. a cytotoxic/nonlinear (MA(sub c)) mechanistic assumption for TCE-induced cancer. Increased risk conditional on effective dose was estimated under MA(sub G) based on seven rodent-bioassay data sets, and under MA, based on mouse hepatotoxicity data. Mean and upper-bound estimates of combined risk calculated by the unified approach were and lt;10(sup -6) and and lt;10(sup -4), respectively, while corresponding estimates based on traditional deterministic methods were and gt;10(sup -5) and and gt;10(sup -4), respectively. It was estimated that no TCE-related harm is likely occur due any plausible residential exposure scenario involving the site. The unified approach illustrated is particularly suited to characterizing risks that involve uncertain and/or diverse mechanisms of action

A non-linear detection of phospho-histone H2AX in EA.hy926 endothelial cells following low-dose X-irradiation is modulated by reactive oxygen species

International Nuclear Information System (INIS)

Large, Martin; Reichert, Sebastian; Hehlgans, Stephanie; Fournier, Claudia; Rödel, Claus; Rödel, Franz

2014-01-01

A discontinuous dose response relationship is a major characteristic of the anti-inflammatory effects of low-dose X-irradiation therapy. Although recent data indicate an involvement of a variety of molecular mechanisms in these characteristics, the impact of reactive oxygen species (ROS) production to give rise or contribute to these phenomena in endothelial cells (EC) remains elusive. HUVEC derived immortalized EA.hy926 cells were stimulated by tumor necrosis factor-α (TNF-α, 20 ng/ml) 4 h before irradiation with doses ranging from 0.3 to 1 Gy. To analyse DNA repair capacity, phospho-histone H2AX foci were assayed at 1 h, 4 h and 24 h after irradiation. ROS production and superoxide dismutase (SOD) activity were analysed by fluorometric 2′,7′-dichlorodihydrofluorescein-diacetate (H2DCFDA) and colorimetric assays. A functional impact of ROS on γH2AX production was analysed by treatment with the scavenger N-acetyl-L-cysteine (NAC). Irrespective of stimulation by TNF-α, EA.hy926 cells revealed a linear dose response characteristic of γH2AX foci detection at 1 h and 4 h after irradiation. By contrast, we observed a discontinuity in residual γH2AX foci detection at 24 h after irradiation with locally elevated values following a 0.5 Gy exposure that was abolished by inhibition of ROS by NAC. Moreover, SOD protein expression was significantly decreased at doses of 0.5 Gy and 0.7 Gy concomitant with a reduced SOD activity. These data implicate a non-linear regulation of ROS production and SOD activity in EA.hy926 EC following irradiation with doses < 1 Gy that may contribute to a discontinuous dose-response relationship of residual γH2AX foci detection

The relationship between external beam radiotherapy dose and chronic urinary dysfunction - A methodological critique

International Nuclear Information System (INIS)

Rosewall, Tara; Catton, Charles; Currie, Geoffrey; Bayley, Andrew; Chung, Peter; Wheat, Janelle; Milosevic, Michael

2010-01-01

Purpose: To perform a methodological critique of the literature evaluating the relationship between external beam radiotherapy dose/volume parameters and chronic urinary dysfunction to determine why consistent associations between dose and dysfunction have not been found. Methods and materials: The radiotherapy literature was reviewed using various electronic medical search engines with appropriate keywords and MeSH headings. Inclusion criteria comprised of; English language articles, published between 1999 and June 2009, incorporating megavoltage external beam photons in standard-sized daily fraction. A methodological critique was then performed, evaluating the factors affected in the quantification of radiotherapy dose and chronic urinary dysfunction. Results: Nine of 22 eligible studies successfully identified a clinically and statistically significant relationship between dose and dysfunction. Accurate estimations of external beam radiotherapy dose were compromised by the frequent use of dosimetric variables which are poor surrogates for the dose received by the lower urinary tract tissue and do not incorporate the effect of daily variations in isocentre and bladder position. The precise categorization of chronic urinary dysfunction was obscured by reliance on subjective and aggregated toxicity metrics which vary over time. Conclusions: A high-level evidence-base for the relationship between external beam radiotherapy dose and chronic urinary dysfunction does not currently exist. The quantification of the actual external beam dose delivered to the functionally important tissues using dose accumulation strategies and the use of objective measures of individual manifestations of urinary dysfunction will assist in the identification of robust relationships between dose and urinary dysfunction for application in widespread clinical practice.

Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

Energy Technology Data Exchange (ETDEWEB)

Scott, Bobby, R., Ph.D.

2003-06-27

applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low

Effects of low doses; Effet des faibles doses

Energy Technology Data Exchange (ETDEWEB)

Le Guen, B. [Electricite de France (EDF-LAM-SCAST), 93 - Saint-Denis (France)

2001-07-01

Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

Radiation dose dependent risk of liver cancer mortality in the German uranium miners cohort 1946–2003

International Nuclear Information System (INIS)

Dufey, F; Walsh, L; Sogl, M; Tschense, A; Schnelzer, M; Kreuzer, M

2013-01-01

An increased risk of mortality from primary liver cancers among uranium miners has been observed in various studies. An analysis of the data from a German uranium miner cohort (the ‘Wismut cohort’) was used to assess the relationship with ionising radiation. To that end the absorbed organ dose due to high and low linear energy transfer radiation was calculated for 58 987 miners with complete information on radiation exposure from a detailed job–exposure matrix. 159 deaths from liver cancer were observed in the follow-up period from 1946 to 2003. Relative risk models with either linear or categorical dependence on high and low linear energy transfer radiation liver doses were fitted by Poisson regression, stratified on age and calendar year. The linear trend of excess relative risk in a model with both low and high linear transfer radiation is −0.8 (95% confidence interval (CI): −3.7, 2.1) Gy −1 and 48.3 (95% CI: −32.0, 128.6) Gy −1 for low and high linear energy transfer radiation, respectively, and thus not statistically significant for either dose. The increase of excess relative risk with equivalent liver dose is 0.57 (95% CI: −0.69, 1.82) Sv −1 . Adjustment for arsenic only had a negligible effect on the radiation risk. In conclusion, there is only weak evidence for an increase of liver cancer mortality with increasing radiation dose in the German uranium miners cohort considered. However, both a lack of statistical power and potential misclassification of primary liver cancer are issues. (paper)

The dose-response relationship for UV-tumorigenesis

International Nuclear Information System (INIS)

Gruijl, F.R. de.

1982-01-01

The main objective of the investigations was to extend the knowledge on experimental UV-carcinogenesis and to use the experimental results as guidelines for developing a dose-response model for UV-carcinogenesis. The animal experiments carried out were all long-term ones. It was decided that - in anticipation of the data to be obtained - a model for such an assessment should be developed using the experimental results available at the start of the present study (1977). This initial study is presented. The results of two animal experiments are presented, which show that UV radiation is capable of inducing a systemic effect that enhances the de novo formation of UV induced tumors. The results of the main experiment are presented. In this experiment groups of mice were subjected to daily exposure to a certain dose of UV radiation in order to find the dose-response relationship. The relation between the daily dose and the duration of the treatment till the appearance of tumors (for instance, as measured by the yield) was ascertained for tumors of different sizes. It appears that the growth of a tumor is dose-independent, and, therefore, only the initiation of a tumor is dose-dependent. Finally an experiment is presented in which it was measured that, if a mouse is subjected to daily UV exposure, the transmission of the epidermis in the shortwave UV region decreases continuously. This decrease is due to hyperplasia of the epidermis, i.e., thickening of the epidermis by an increase in the number of cells per unit surface area. (Auth.)

Risk equivalent of exposure versus dose of radiation

International Nuclear Information System (INIS)

Bond, V.P.

1986-01-01

This report describes a risk analysis study of low-dose irradiation and the resulting biological effects on a cell. The author describes fundamental differences between the effects of high-level exposure (HLE) and low-level exposure (LLE). He stresses that the concept of absorbed dose to an organ is not a dose but a level of effect produced by a particular number of particles. He discusses the confusion between a linear-proportional representation of dose limits and a threshold-curvilinear representation, suggesting that a LLE is a composite of both systems

Quantifying the dose-response of walking in reducing coronary heart disease risk: meta-analysis.

Science.gov (United States)

Zheng, Henry; Orsini, Nicola; Amin, Janaki; Wolk, Alicja; Nguyen, Van Thi Thuy; Ehrlich, Fred

2009-01-01

The evidence for the efficacy of walking in reducing the risk of and preventing coronary heart disease (CHD) is not completely understood. This meta-analysis aimed to quantify the dose-response relationship between walking and CHD risk reduction for both men and women in the general population. Studies on walking and CHD primary prevention between 1954 and 2007 were identified through Medline, SportDiscus and the Cochrane Database of Systematic Reviews. Random-effect meta-regression models were used to pool the relative risks from individual studies. A total of 11 prospective cohort studies and one randomized control trial study met the inclusion criteria, with 295,177 participants free of CHD at baseline and 7,094 cases at follow-up. The meta-analysis indicated that an increment of approximately 30 min of normal walking a day for 5 days a week was associated with 19% CHD risk reduction (95% CI = 14-23%; P-heterogeneity = 0.56; I (2) = 0%). We found no evidence of heterogeneity between subgroups of studies defined by gender (P = 0.67); age of the study population (P = 0.52); or follow-up duration (P = 0.77). The meta-analysis showed that the risk for developing CHD decreases as walking dose increases. Walking should be prescribed as an evidence-based effective exercise modality for CHD prevention in the general population.

Dairy products consumption and risk of type 2 diabetes: systematic review and dose-response meta-analysis.

Directory of Open Access Journals (Sweden)

Dengfeng Gao

Full Text Available BACKGROUND: The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM, but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies, low-fat dairy products (8 studies, cheese (7 studies and yogurt (7 studies and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97 and 0.88 (0.84-0.93 for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93 and 0.91 (0.82-1.00 for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

Why we need new approaches to low-dose risk modeling

International Nuclear Information System (INIS)

Alvarez, J.L.; Seiler, F.A.

1996-01-01

The linear no-threshold model for radiation effects was introduced as a conservative model for the design of radiation protection programs. The model has persisted not only as the basis for such programs, but has come to be treated as a dogma and is often confused with scientific fact. In this examination a number of serious problems with the linear no-threshold model of radiation carcinogenesis were demonstrated, many of them invalidating the hypothesis. It was shown that the relative risk formalism did not approach 1 as the dose approaches zero. When morality ratios were used instead, the data in the region below 0.3 Sv were systematically below the predictions of the linear model. It was also shown that the data above 0.3 Sv were of little use in formulating a model at low doses. In addition, these data are valid only for doses accumulated at high dose rates, and there is no scientific justification for using the model in low-dose, low-dose-rate extrapolations for purposes of radiation protection. Further examination of model fits to the Japanese survivor data were attempted. Several such models were fit to the data including an unconstrained linear, linear-square root, and Weibull, all of which fit the data better than the relative risk, linear no-threshold model. These fits were used to demonstrate that the linear model systematically over estimates the risk at low doses in the Japanese survivor data set. It is recommended here that an unbiased re-analysis of the data be undertaken and the results used to construct a new model, based on all pertinent data. This model could then form the basis for managing radiation risks in the appropriate regions of dose and dose rate

Non-Linear Relationships between Aflatoxin B1 Levels and the Biological Response of Monkey Kidney Vero Cells

Directory of Open Access Journals (Sweden)

Mendel Friedman

2013-08-01

Full Text Available Aflatoxin-producing fungi contaminate food and feed during pre-harvest, storage and processing periods. Once consumed, aflatoxins (AFs accumulate in tissues, causing illnesses in animals and humans. Most human exposure to AF seems to be a result of consumption of contaminated plant and animal products. The policy of blending and dilution of grain containing higher levels of aflatoxins with uncontaminated grains for use in animal feed implicitly assumes that the deleterious effects of low levels of the toxins are linearly correlated to concentration. This assumption may not be justified, since it involves extrapolation of these nontoxic levels in feed, which are not of further concern. To develop a better understanding of the significance of low dose effects, in the present study, we developed quantitative methods for the detection of biologically active aflatoxin B1 (AFB1 in Vero cells by two independent assays: the green fluorescent protein (GFP assay, as a measure of protein synthesis by the cells, and the microculture tetrazolium (MTT assay, as a measure of cell viability. The results demonstrate a non-linear dose-response relationship at the cellular level. AFB1 at low concentrations has an opposite biological effect to higher doses that inhibit protein synthesis. Additional studies showed that heat does not affect the stability of AFB1 in milk and that the Vero cell model can be used to determine the presence of bioactive AFB1 in spiked beef, lamb and turkey meat. The implication of the results for the cumulative effects of low amounts of AFB1 in numerous foods is discussed.

Patient doses and radiation risks in film-screen mammography in Finland

International Nuclear Information System (INIS)

Servomaa, A.; Parviainen, T.; Komppa, T.

1995-01-01

Screen-film mamography is the most sensitive method for the early detection of breast cancer. Breast doses in mamography should be measured for several reasons, especially for the evaluation of patient risk in a screening programme, but also for the assessment and comparison of imaging techniques and equipment performance. In this study, the factors affecting patient doses were assessed by making performance and patient dose measurements; about 50 mammographic units used for screening were included in the study. The lifetime risk as a function of age at exposure was calculated using the average glandular dose, the relative risk model shown in the BEIR V report, and the breast cancer mortality in Finland. The mean surface dose of a 4.5 cm thick phantom was 6.3 mGy, and the mean glandular dose 1.0 mGy. Analysis of the surface dose with respect to film optical density, relative speed of film processing, sensitivity of image receptors, and antiscatter grid showed that the mean surface dose could be decreased by more than 50%. For the screened age group of 50 to 59 years, the risk of exposure-induced death (REID) of breast cancer is about 1.4 x 10 -6 mSv -1 , and the average loss of life expectancy due to the radiation-induced breast cancer deaths (LLE/REID) is about 9.5 years. (Author)

Parametric relationships for gamma dose and irradiation homogeneity in a sewage sludge irradiator

International Nuclear Information System (INIS)

Krishnamurthy, K.

1986-01-01

A study on the inter-relationships between factors governing γ dose and irradiation homogeneity in a sewage sludge irradiator is presented here. The analysis involves a 60 Co irradiator of cylindrical irradiation geometry with batchwise operation for hygienisation of liquid sludge. The influence of the parameters such as the source-target geometry, strength of 60 Co sources in the irradiator, hygienisation dose and rheological and hydraulic characteristics of sewage sludge on the selection of the three critical factors viz. the pumping rate (P) required to maintain turbulent flow regime in the irradiation zone; the mininum re-circulation time (Tsub(m)) essential to achieve a certain degree of homogeneity of dose absorption in the fluid; and the irradiation time (Tsub(i)) required to impart the necessary dose for the desired hygienisation effect in the sludge has been discussed in detail and inter-relationships among these three factors have been worked out. The applicability of the relationships to a typical operating plant has also been elucidated. (author)

Acute Radiation Risk and BRYNTRN Organ Dose Projection Graphical User Interface

Science.gov (United States)

Cucinotta, Francis A.; Hu, Shaowen; Nounu, Hateni N.; Kim, Myung-Hee

2011-01-01

The integration of human space applications risk projection models of organ dose and acute radiation risk has been a key problem. NASA has developed an organ dose projection model using the BRYNTRN with SUM DOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUM DOSE are a Baryon transport code and an output data processing code, respectively. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN. A GUI for the ARR and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. BRYNTRN code operation requires extensive input preparation. Only a graphical user interface (GUI) can handle input and output for BRYNTRN to the response models easily and correctly. The purpose of the GUI development for ARRBOD is to provide seamless integration of input and output manipulations for the operations of projection modules (BRYNTRN, SLMDOSE, and the ARR probabilistic response model) in assessing the acute risk and the organ doses of significant Solar Particle Events (SPEs). The assessment of astronauts radiation risk from SPE is in support of mission design and operational planning to manage radiation risks in future space missions. The ARRBOD GUI can identify the proper shielding solutions using the gender-specific organ dose assessments in order to avoid ARR symptoms, and to stay within the current NASA short-term dose limits. The quantified evaluation of ARR severities based on any given shielding configuration and a specified EVA or other mission

Diabetogenic action of streptozotocin: relationship of dose to metabolic response

Science.gov (United States)

Junod, Alain; Lambert, André E.; Stauffacher, Werner; Renold, Albert E.

1969-01-01

The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections. PMID:4241908

Using plant biomonitors and flux modelling to develop O3 dose-response relationships in Catalonia

International Nuclear Information System (INIS)

Filella, Iolanda; Pen-tilde uelas, Josep; Ribas, Angela

2005-01-01

We used tobacco Bel-W3 biomonitoring data and ozone flux modelling (WINDEP model) with the aim of developing the absorbed dose-response relationship, and comparing this approach with the most commonly used AOT40 (the sum of hourly ozone concentrations above a cut-off of 40 ppb during daylight hours, when global radiation exceeds 50 W m -2 ) in the estimation of exposure-damage curves. Leaf damage values were more related to OAD 15days,potential (potential ozone absorbed dose calculated over 15 consecutive days) than to AOT40 in all the studied stations. An OAD 15days,potential of 180 mg m -2 was found to be the threshold for damage to the most sensitive species in this region under well watered conditions. The results show the applicability of the flux approach for risk assessment at the local scale, the improvement of the ozone damage estimation when the potential absorbed dose is modelled and used instead of just the ozone exposure, and finally, the possibilities opened by the use of biomonitoring networks. - Modelling of biomonitors ozone absorbed dose improves damage estimation in comparison with exposure indices such as AOT40

Daytime napping and risk of type 2 diabetes: a meta-analysis of prospective studies.

Science.gov (United States)

Chen, Guo-Chong; Liu, Meng-Meng; Chen, Li-Hua; Xu, Jia-Ying; Hidayat, Khemayanto; Li, Fu-Rong; Qin, Li-Qiang

2017-06-13

Prospective studies reported inconsistent findings on the relationship between daytime napping and risk of type 2 diabetes (T2D). Categorized and dose-response meta-analyses were performed to quantify this relation. Potentially eligible studies were identified by searching PubMed and Embase databases. Dose-response effects were assessed by the generalized least squares trend estimation and study-specific summary relative risks (RRs) with 95% confidence intervals (CIs) were computed with a random-effects model. Seven prospective studies including one US, four European, and two Chinese cohorts involving 249,077 participants and 13,237 cases of T2D were included. The overall analyses showed a 17% increased risk of T2D when comparing habitual nappers with non-nappers (RR = 1.17, 95% CI 1.08-1.27). By region, the summary RR was 1.21 (95% CI 1.17-1.26), 1.15 (95% CI 1.03-1.30) and 1.23 (95% CI 0.87-1.73) for the US, European, and Chinese studies, respectively. Limiting to five studies that excluded subjects with known major chronic disorders yielded a summary RR of 1.16 (95% CI 1.03-1.30). A dose-response analysis suggested an 11% (95% CI 7-16%) increased T2D risk for each increment in daytime napping of 30 min/day and, despite no evidence for nonlinearity (P nonlinearity  = 0.65), the increased risk of T2D for short nap (napping is associated with an increased risk of T2D. Given the limited number of cohorts and inconsistency in terms of methodological and population characteristics across these cohorts, residual confounders and/or reverse causality cannot be fully addressed, and our findings should be interpreted with great caution. Future well-designed prospective studies are still warranted.

Non-linear relationship between oxygen uptake and power output in the Astrand nomogram-old data revisited.

Science.gov (United States)

Zoladz, J A; Szkutnik, Z; Majerczak, J; Duda, K; Pedersen, P K

2007-06-01

For the last decade there have been considerable discussion concerning the linearity / non-linearity of the oxygen uptake (V(O2)) - power output (W) relationship with strong experimental evidence of non-linearity provided mainly by breath-by-breath measurements. In this study, we attempted to answer the question whether the V(O2) - W relationship in the Astrand nomogram, as presented in the Textbook of Work Physiology, P.-O. Astrand et al. (2003), page 281, based on the Douglas bag method, is indeed linear, as stated by the authors before, or if a change point in V(O2), described by Zoladz et al. (1998) Eur J Appl Physiol 78: 369-377, can possibly be detected in those data. The V(O2) - W data were taken from the Astrand nomogram referenced above and from the Table 9.5 on page 282 in the same reference and tested for the presence of the change point in V(O2), using our two-phase model (see the reference above). In the first phase, a linear V(O2) - W relationship was assumed, whereas in the second one (above the so-called change point) an additional increase in V(O2) above the values expected from the linear model was allowed. It was found that in the data taken from the Astrand nomogram (data for men), as well as in the data taken from the Table 9.5, statistically significant change points in V(O2) were present at the power output of 150 W. The documentation of the presence of a change point in the V(O2) - W relationship in the Astrand data provides further evidence for the existence of a non-linearity in the V(O2) - W relationship in incremental exercise tests of humans, also in V(O2) data based upon the Douglas bag method.

The role of uncertainty analysis in dose reconstruction and risk assessment

International Nuclear Information System (INIS)

Hoffman, F.O.; Simon, S.L.; Thiessen. K.M.

1996-01-01

Dose reconstruction and risk assessment rely heavily on the use of mathematical models to extrapolate information beyond the realm of direct observation. Because models are merely approximations of real systems, their predictions are inherently uncertain. As a result, full disclosure of uncertainty in dose and risk estimates is essential to achieve scientific credibility and to build public trust. The need for formal analysis of uncertainty in model predictions was presented during the nineteenth annual meeting of the NCRP. At that time, quantitative uncertainty analysis was considered a relatively new and difficult subject practiced by only a few investigators. Today, uncertainty analysis has become synonymous with the assessment process itself. When an uncertainty analysis is used iteratively within the assessment process, it can guide experimental research to refine dose and risk estimates, deferring potentially high cost or high consequence decisions until uncertainty is either acceptable or irreducible. Uncertainty analysis is now mandated for all ongoing dose reconstruction projects within the United States, a fact that distinguishes dose reconstruction from other types of exposure and risk assessments. 64 refs., 6 figs., 1 tab

A Non-linear "Inflation-Relative Prices Variability" Relationship: Evidence from Latin America

OpenAIRE

Mª Ángeles Caraballo Pou; Carlos Dabús; Diego Caramuta

2006-01-01

This paper presents evidence on a non-linear "inflation-relative prices variability" relationship in three Latin American countries with very high inflation experiences: Argentina, Brazil and Peru. More precisely, and in contrast to results found in previous literature for similar countries, we find a non-concave relation at higher inflation regimes, i.e. when inflation rate surpasses certain threshold. This non-concavity is mainly explained by the unexpected component of inflation, which sug...

Application of the Generalized Nonlinear Complementary Relationship for Estimating Evaporation in North China

Science.gov (United States)

Yu, M.; Wu, B.

2017-12-01

As an important part of the coupled Eco-Hydrological processes, evaporation is the bond for exchange of energy and heat between the surface and the atmosphere. However, the estimation of evaporation remains a challenge compared with other main hydrological factors in water cycle. The complementary relationship which proposed by Bouchet (1963) has laid the foundation for various approaches to estimate evaporation from land surfaces, the essence of the principle is a relationship between three types of evaporation in the environment. It can simply implemented with routine meteorological data without the need for resistance parameters of the vegetation and bare land, which are difficult to observed and complicated to estimate in most surface flux models. On this basis the generalized nonlinear formulation was proposed by Brutsaert (2015). The daily evaporation can be estimated once the potential evaporation (Epo) and apparent potential evaporation (Epa) are known. The new formulation has a strong physical basis and can be expected to perform better under natural water stress conditions, nevertheless, the model has not been widely validated over different climate types and underlying surface patterns. In this study, we attempted to apply the generalized nonlinear complementary relationship in North China, three flux stations in North China are used for testing the universality and accuracy of this model against observed evaporation over different vegetation types, including Guantao Site, Miyun Site and Huailai Site. Guantao Site has double-cropping systems and crop rotations with summer maize and winter wheat; the other two sites are dominated by spring maize. Detailed measurements of meteorological factors at certain heights above ground surface from automatic weather stations offered necessary parameters for daily evaporation estimation. Using the Bowen ratio, the surface energy measured by the eddy covariance systems at the flux stations is adjusted on a daily scale

Therapeutic effects of low radiation doses

Energy Technology Data Exchange (ETDEWEB)

Trott, K.R. (Dept. of Radiation Biology, St. Bartholomew' s Medical College, London (United Kingdom))

1994-01-01

This editorial explores the scientific basis of radiotherapy with doses of < 1 Gy for various non-malignant conditions, in particular dose-effect relationships, risk-benefit considerations and biological mechanisms. A review of the literature, particularly clinical and experimental reports published more than 50 years ago was conducted to clarify the following problems. 1. The dose-response relationships for the therapeutic effects on three groups of conditions: non-malignant skin disease, arthrosis and other painful degenerative joint disorders and anti-inflammatory radiotherapy; 2. risks after radiotherapy and after the best alternative treatments; 3. the biological mechanisms of the different therapeutic effects. Radiotherapy is very effective in all three groups of disease. Few dose-finding studies have been performed, all demonstrating that the optimal doses are considerable lower than the generally recommended doses. In different conditions, risk-benefit analysis of radiotherapy versus the best alternative treatment yields very different results: whereas radiotherapy for acute postpartum mastitis may not be justified any more, the risk-benefit ratio of radiotherapy of other conditions and particularly so in dermatology and some anti-inflammatory radiotherapy appears to be more favourable than the risk-benefit ratio of the best alternative treatments. Radiotherapy can be very effective treatment for various non-malignant conditions such as eczema, psoriasis, periarthritis humeroscapularis, epicondylitis, knee arthrosis, hydradenitis, parotitis and panaritium and probably be associated with less acute and long-term side effects than similarly effective other treatments. Randomized clinical studies are required to find the optimal dosage which, at present, may be unnecessarily high.

Analysis of thermal-dose response to heat

International Nuclear Information System (INIS)

Storm, F.; Roe, D.; Drury, B.

1987-01-01

The authors reasoned that if hyperthermia alone has a clinical anti-tumor effect, response should have a thermal dose relationship. The authors analyzed 100 patients with advanced cancer treated with magnetic-induction. Three methods of determining thermal dose were used: (A) t1x10, the lowest temperature sustained throughout the tumor for 30-60min during the first of ten daily treatments, which represents one usual course of ten hourly sessions; (B) t43 (equivalent minutes at 43C) which accounts for non-linear tumor heating by combining serially measured temperatures during the first treatment with a mathematical description of the time-temperature relationship for thermal inactivation or damage; (C) Ct43 (cumulative t43), which represents the t43 value multiplied by the actual number of subsequent daily treatments received. Response was defined as CR+PR+MR. The results show a statistically significant effect of heat alone for t1x10, t43, and Ct43. These analyses demonstrate a thermal-dose relationship between hyperthermia therapy and tumor response as a sole independent variable, which indicates that heat therapy has clinical anti-cancer activity

Reproductive factors, menopausal hormone therapies and primary liver cancer risk: a systematic review and dose-response meta-analysis of observational studies.

Science.gov (United States)

Zhong, Guo-Chao; Liu, Yan; Chen, Nan; Hao, Fa-Bao; Wang, Kang; Cheng, Jia-Hao; Gong, Jian-Ping; Ding, Xiong

2016-12-01

A striking gender disparity in the incidence and outcome of primary liver cancer (PLC) has been well recognized. Mounting evidence from basic research suggests that hormonal factors may be involved in the gender disparity of PLC. Whether hormonal exposures in human subjects are associated with PLC risk is largely unknown. Whether reproductive factors and use of menopausal hormone therapies (MHTs) in women are associated with PLC risk remains controversial. We conducted this study to clarify this issue. PubMed and EMBASE were searched to July, 2016 for studies published in English or Chinese. Observational studies (cohort, nested case-control and case-control) that provided risk estimates of reproductive factors, MHTs and PLC risk were eligible. The quality of included studies was determined based on the Newcastle-Ottawa quality assessment scale. Summary risk ratios (RRs) were calculated using a random-effects model. Dose-response analysis was conducted where possible. Fifteen peer-reviewed studies, involving 1795 PLC cases and 2 256 686 women, were included. Overall meta-analyses on parity and PLC risk did not find any significant associations; however, when restricting to studies with PLC cases ≥100, increasing parity was found to be significantly associated with a decreased risk of PLC [RR for the highest versus lowest parity 0.67, 95% CI 0.52, 0.88; RR for parous versus nulliparous 0.71, 95% CI 0.53, 0.94; RR per one live birth increase 0.93, 95% CI 0.88, 0.99]. A J-shaped relationship between parity and PLC risk was identified (P non-linearity  Parity is associated with PLC risk in a J-shaped dose-response pattern. Late age at menarche and ever use of MHT are associated with a reduced risk of PLC, whereas there is no association of ever use of ET and EPT, age at first birth, or spontaneous and induced abortion with PLC risk. Compared to women with no history of oophorectomy, those with a history of oophorectomy are at an increased risk of PLC. Our findings

Low-dose effect on blood chromosomes

International Nuclear Information System (INIS)

Pohl-Rueling, J.

1992-01-01

Linear dose response relationships of biological effects at low doses are experimentally and theoretically disputed. Structural chromosome aberration rates at doses ranging from normal background exposures up to about 30 mGy/yr in vivo and up to 50 mGy in vitro were investigated by the author and other scientists. Results are comparable and dose effect curves reveal following shapes; within the normal burden and up to 2-10 mGy/yr in vivo rates they increase sharply to about 3-6 times the lowest values; subsequent doses either from natural, occupational or accidental exposures up to about 30 mGy/yr yield either constant aberration rates, assuming a plateau, or perhaps even a decrease. In vitro experiments show comparable results up to 50 mGy. Other biological effects seem to have similar dose dependencies. The non-linearity of low-dose effects can be explained by induction of repair enzymes at certain damage to the DNA. This hypothesis is sustained experimentally and theoretically by several papers in literature. (author). 14 refs., 5 figs

SU-F-18C-12: On the Relationship of the Weighted Dose to the Surface Dose In Abdominal CT - Patient Size Dependency

Energy Technology Data Exchange (ETDEWEB)

Zhou, Y; Scott, A; Allahverdian, J [Cedars-Sinai Medical Center, Los Angeles, CA (United States)

2014-06-15

Purpose: It is possible to measure the patient surface dose non-invasively using radiolucent dosimeters. However, the patient size specific weighted dose remains unknown. We attempted to study the weighted dose to surface dose relationship as the patient size varies in abdominal CT. Methods: Seven abdomen phantoms (CIRS TE series) simulating patients from an infant to a large adult were used. Size specific doses were measured with a 100 mm CT chamber under axial scans using a Siemens Sensation 64 (mCT) and a GE 750 HD. The scanner settings were 120 kVp, 200 mAs with fully opened collimations. Additional kVps (80, 100, 140) were added depending on the phantom sizes. The ratios (r) of the weighted CT dose (Dw) to the surface dose (Ds) were related to the phantom size (L) defined as the diameter resulting the equivalent cross-sectional area. Results: The Dw versus Ds ratio (r) was fitted to a linear relationship: r = 1.083 − 0.007L (R square = 0.995), and r = 1.064 − 0.007L (R square = 0.953), for Siemens Sensation 64 and GE 750 HD, respectively. The relationship appears to be independent of the scanner specifics. Conclusion: The surface dose to the weighted dose ratio decreases linearly as the patient size increases. The result is independent of the scanner specifics. The result can be used to obtain in vivo CT dosimetry in abdominal CT.

SU-F-18C-12: On the Relationship of the Weighted Dose to the Surface Dose In Abdominal CT - Patient Size Dependency

International Nuclear Information System (INIS)

Zhou, Y; Scott, A; Allahverdian, J

2014-01-01

Purpose: It is possible to measure the patient surface dose non-invasively using radiolucent dosimeters. However, the patient size specific weighted dose remains unknown. We attempted to study the weighted dose to surface dose relationship as the patient size varies in abdominal CT. Methods: Seven abdomen phantoms (CIRS TE series) simulating patients from an infant to a large adult were used. Size specific doses were measured with a 100 mm CT chamber under axial scans using a Siemens Sensation 64 (mCT) and a GE 750 HD. The scanner settings were 120 kVp, 200 mAs with fully opened collimations. Additional kVps (80, 100, 140) were added depending on the phantom sizes. The ratios (r) of the weighted CT dose (Dw) to the surface dose (Ds) were related to the phantom size (L) defined as the diameter resulting the equivalent cross-sectional area. Results: The Dw versus Ds ratio (r) was fitted to a linear relationship: r = 1.083 − 0.007L (R square = 0.995), and r = 1.064 − 0.007L (R square = 0.953), for Siemens Sensation 64 and GE 750 HD, respectively. The relationship appears to be independent of the scanner specifics. Conclusion: The surface dose to the weighted dose ratio decreases linearly as the patient size increases. The result is independent of the scanner specifics. The result can be used to obtain in vivo CT dosimetry in abdominal CT

Competing risk theory and radiation risk assessment

International Nuclear Information System (INIS)

Groer, P.G.

1980-01-01

New statistical procedures are applied to estimate cumulative distribution functions (c.d.f.), force of mortality, and latent period for radiation-induced malignancies. It is demonstrated that correction for competing risks influences the shape of dose response curves, estimates of the latent period, and of the risk from ionizing radiations. The equivalence of the following concepts is demonstrated: force of mortality, hazard rate, and age or time specific incidence. This equivalence makes it possible to use procedures from reliability analysis and demography for radiation risk assessment. Two methods used by reliability analysts - hazard plotting and total time on test plots - are discussed in some detail and applied to characterize the hazard rate in radiation carcinogenesis. C.d.f.'s with increasing, decreasing, or constant hazard rate have different shapes and are shown to yield different dose-response curves for continuous irradiation. Absolute risk is shown to be a sound estimator only if the force of mortality is constant for the exposed and the control group. Dose-response relationships that use the absolute risk as a measure for the effect turn out to be special cases of dose-response relationships that measure the effect with cumulative incidence. (H.K.)

Thyroid nodules in the population living around semipalatinsk nuclear test site. Possible implications for dose-response relationships study

International Nuclear Information System (INIS)

Zhumadilov, Z.

2006-01-01

The risk of radiation-induced nodules is higher than the risk for radiation-induced cancer. Risk factors and specific modifiers of the dose-response relationship may vary among different populations and not be well recognized. Many thyroid studies have considered thyroid nodularity itself, but not specific morphological types of thyroid nodules. There are many specific types of thyroid nodules which follow a morphological classification of thyroid lesions, including some congenital and tumor-like conditions. Modern equipment and technique can help us to identify particular specific types of thyroid nodules. In this study we report some results of a clinically applicable approach to materials derived from three studies. From 1999 through 2002, we have screened 571 current residents from 4 exposed and 1 control village near the Semipalatinsk Nuclear Test Site area, who were of similar ages (<20) at the time of major radiation fallout events at the Semipalatinsk Nuclear Test Site (SNTS). Prevalent nodules were identified by ultrasound and fine-needle aspiration biopsy, cytopathology results. Analysis of ultrasound images and cytopathology of thyroid lesions among exposed and non-exposed population allowed us to distinguish some interesting ultrasound features for specific types of thyroid nodules. We believe that it would be interesting and possibly more informative for thyroid dosimetry studies to consider specific morphological types of thyroid nodules. We need more detailed research to clarify the feasibility of applying these findings for study of the dose-response relationship. (author)

Health effect of low dose/low dose rate radiation

International Nuclear Information System (INIS)

Kodama, Seiji

2012-01-01

The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

Cytogenetic effects of low-dose radiation

International Nuclear Information System (INIS)

Metalli, P.

1983-01-01

The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

Estimates of radiation doses and cancer risk from food intake in Korea

International Nuclear Information System (INIS)

Moon, Eun Kyeong; Lee, Won Jin; Ha, Wi Ho; Seo, Song Won; Jin, Young Woo; Jeong, Kyu Hwan; Yoon, Hae Jung; Kim, Hyoung Soo; Hwang, Myung Sil; Choi, Hoon

2016-01-01

After the Fukushima Daiichi nuclear power plant accident, a widespread public concern for radiation exposure through the contamination of domestic or imported food has continued worldwide. Because the internal exposure from contaminated food is an important consideration for human health effect, some studies for estimating radiation doses and cancer risk from the Fukushima nuclear accident have been conducted in several countries (1). The aims of the study is to estimate internal radiation dose and lifetime risks of cancer from food ingestion in Korean population. Our findings suggest no discernible increase n radiation doses or excess fatal cancer risk from food ingestion at this stage in Korea, and provide scientific evidence of the risk communication with general public associated with low-dose radiation exposure.

Estimates of radiation doses and cancer risk from food intake in Korea

Energy Technology Data Exchange (ETDEWEB)

Moon, Eun Kyeong; Lee, Won Jin [Korea University, Seoul (Korea, Republic of); Ha, Wi Ho; Seo, Song Won; Jin, Young Woo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Jeong, Kyu Hwan [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Yoon, Hae Jung; Kim, Hyoung Soo; Hwang, Myung Sil [Ministry of Food and Drug Safety, Cheongju (Korea, Republic of); Choi, Hoon [Wonkwang University, Iksan (Korea, Republic of)

2016-04-15

After the Fukushima Daiichi nuclear power plant accident, a widespread public concern for radiation exposure through the contamination of domestic or imported food has continued worldwide. Because the internal exposure from contaminated food is an important consideration for human health effect, some studies for estimating radiation doses and cancer risk from the Fukushima nuclear accident have been conducted in several countries (1). The aims of the study is to estimate internal radiation dose and lifetime risks of cancer from food ingestion in Korean population. Our findings suggest no discernible increase n radiation doses or excess fatal cancer risk from food ingestion at this stage in Korea, and provide scientific evidence of the risk communication with general public associated with low-dose radiation exposure.

Vitamin E and risk of age-related cataract: a meta-analysis.

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Zhang, Yufei; Jiang, Wenjie; Xie, Zhutian; Wu, Wenlong; Zhang, Dongfeng

2015-10-01

We conducted a meta-analysis to evaluate the relationship between vitamin E and age-related cataract (ARC). The fixed- or random-effect model was selected based on heterogeneity. Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Begg's test. The dose-response relationship was assessed by a restricted cubic spline model. Relevant studies were identified by a search of PubMed and the Cochrane Library to May 2014, without language restrictions. Studies involved samples of people of all ages. Dietary vitamin E intake, dietary and supplemental vitamin E intake, and high serum tocopherol levels were significantly associated with decreased risk of ARC, the pooled relative risk was 0·73 (95% CI 0·58, 0·92), 0·86 (95% CI 0·75, 0·99) and 0·77 (95% CI 0·66, 0·91), respectively. Supplemental vitamin E intake was non-significantly associated with ARC risk (relative risk=0·92; 95% CI 0·78, 1·07). The findings from dose-response analysis showed evidence of a non-linear association between dietary vitamin E intake and ARC. The risk of ARC decreased with dietary vitamin E intake from 7 mg/d (relative risk=0·94; 95% CI 0·90, 0·97). The findings of the meta-analysis indicated that dietary vitamin E intake, dietary and supplemental vitamin E intake, and high level of serum tocopherol might be significantly associated with reduced ARC risk.

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

Science.gov (United States)

Yang, Yi-Sun; Kornelius, Edy; Chiou, Jeng-Yuan; Lai, Yung-Rung; Lo, Shih-Chang; Peng, Chiung-Huei; Huang, Chien-Ning

2017-12-01

Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

Brand relationships and risk: influence of risk avoidance and gender on brand consumption

OpenAIRE

Lee, Seung-Hee; Workman, Jane E.; Jung, Kwangho

2016-01-01

Recent brand relationship research has paid attention to brand love, brand credibility, and brand loyalty. In market and society, various collaborations and co-creations derived from brand relationships generate various social network markets and open business innovations. Brand relationships and collaborative forms heavily depend on risk taking or risk avoidance. However, few studies have examined how brand relationship is related to risk avoidance. The purpose of this study is to investigat...

Understanding the Puzzling Risk-Return Relationship for Housing

OpenAIRE

Lu Han

2013-01-01

Standard theory predicts a positive relationship between risk and return, yet recent data show that housing returns vary positively with risk in some markets but negatively in others. This paper rationalizes these cross-market differences in the risk-return relationship for housing, and in so doing, explains the puzzling negative relationship. The paper shows that when the current house provides a hedge against the risk associated with the future housing consumption, households are willing to...

[Efficacy of low-dose tadalafil on ED assessed by Self-Esteem and Relationship Questionnaire].

Science.gov (United States)

Li, Jing-Ping; Li, Fei; Guo, Wen-Bin; Zhou, Qi-Zhao; Liu, Cun-Dong; Mao, Xiang-Ming; Tan, Wan-Long; Zheng, Shao-Bin

2010-12-01

To explore the effects of low-dose oral tadalafil on self-esteem, confidence and sexual relationship in ED patients. We treated 17 ED patients with oral tadalafil at the low dose of 5 mg once daily for 12 weeks, and used the paired t test to compare their scores on The Self-Esteem and Relationship Questionnaire (SEAR) and IIEF-5 and the results of nocturnal penile tumescence (NPT) obtained by nocturnal electrobioimpedance volumetric assessment (NEVA) before and after the medication. The scores on SEAR and IIEF-5 were significantly increased (P P Low-dose oral tadalafil once daily can significantly improve the self-esteem, confidence, sexual relationship satisfaction and NPT of ED patients.

Risks and radiation doses due to residential radon in Germany

International Nuclear Information System (INIS)

Beck, T.R.

2017-01-01

The population-averaged risk rate and the annual average effective dose due to residential radon in Germany were calculated. The calculations were based on an epidemiological approach taking into account the age- and gender-specific lung cancer incidence rates for the German population and the excess relative risk of 0.16 per 100 Bq.m"-"3 for residential radon. In addition, the risk estimates adjusted for the smoking habits were determined. The population-averaged risk rate for the whole population was estimated with 4.1.10"-"5 y"-"1 (95% confidence interval (CI) 1.4.10"-"5 - 7.6.10"-"5 y"-"1). Residential radon causes a detriment per year of 3.3.10"-"5 y"-"1 (95% CI 1.1.10"-"5 - 6.0.10"-"5 y"-"1), which corresponds to an annual average effective dose of 0.6 mSv (95% CI 0.2-1.1 mSv). Annually, ∼3400 lung cancer incidences are attributed to residential radon. The results from the epidemiological approach exercised in this study are considerably lower than the effective dose, which would be obtained from the dose conversion coefficient calculated using biokinetic and dosimetric models. (author)

Rationale for nonlinear dose response functions of power greater or less than one

International Nuclear Information System (INIS)

Baum, J.W.

1977-08-01

Risk estimates and radiation protection standards are generally made using a nonthreshold premise and linear extrapolations from existing data to estimate biological radiation effects at lower doses and at lower dose rates. This seems reasonable in light of the variety of shapes of dose-effect relations which have been observed both in animal studies and in human epidemiological studies. An unexplained observation in several studies was a response which followed a power function of dose with exponent less than one. One explanation offered for this type of response in humans was a postulated population of heterogeneous sensitivity. An alternate, though related, way of considering this question is in terms of multiple-stresses, and this postulate is discussed

Revision of risk estimates and implications for dose limits

International Nuclear Information System (INIS)

Clarke, R.H.

1989-01-01

It has been apparent for some time that our estimates of the risks associated with exposure to ionizing radiation must be increased above those values reported by UNSCEAR in 1977 an dused by ICRP to form their present recommendations. NRPB foresaw some of these changes and introduced interim advice within the UK to restrict exposures of wordkers and members of the public to levels below the existing limits. Since that advice was given, UNSCEAR has produced a 1988 report reviewing human data to provide new estimates of risks associated with exposure at high doses and high doserates. These risk figures are up to 4 times higher than when UNSCEAR reported in 1977. In this paper, the reasons for the changes in the estimates of risk will be described and the current NRPB guidelines for risk factors for protection purposes will be presented. The implications of these new risk factors for the setting of dose limits will then be discussed. (Author). 10 refs.; 2 tabs

Average annual doses, lifetime doses and associated risk of cancer death for radiation workers in various fuel fabrication facilities in India

International Nuclear Information System (INIS)

Iyer, P.S.; Dhond, R.V.

1980-01-01

Lifetime doses based on average annual doses are estimated for radiation workers in various fuel fabrication facilities in India. For such cumulative doses, the risk of radiation-induced cancer death is computed. The methodology for arriving at these estimates and the assumptions made are discussed. Based on personnel monitoring records from 1966 to 1978, the average annual dose equivalent for radiation workers is estimated as 0.9 mSv (90 mrem), and the maximum risk of cancer death associated with this occupational dose as 1.35x10 -5 a -1 , as compared with the risk of death due to natural causes of 7x10 -4 a -1 and the risk of death due to background radiation alone of 1.5x10 -5 a -1 . (author)

Radiation dose and cancer risk among pediatric patients undergoing interventional neuroradiology procedures

International Nuclear Information System (INIS)

Thierry-Chef, Isabelle; Simon, Steven L.; Miller, Donald L.

2006-01-01

During interventional neuroradiology procedures, patients can be exposed to moderate to high levels of radiation. Special considerations are required to protect children, who are generally more sensitive to the short- and long-term detrimental effects of radiation exposure. Estimates of dose to the skin of children from certain interventional procedures have been published elsewhere, but we are not aware of data on dose to the brain or on the long-term risk of cancer from brain radiation. Our goals were to estimate radiation doses to the brain in 50 pediatric patients who had undergone cerebral embolization and to assess their lifetime risks of developing radiation-related brain cancer. Entrance-peak skin dose and various assumptions on conditions of exposure were used as input for dosimetric calculations to estimate the spatial pattern of dose within the brain and the average dose to the whole brain for each child. The average dose and the age of the child at time of exposure were used to estimate the lifetime risk of developing radiation-related brain cancer. Among the 50 patients, average radiation doses to the brain were estimated to vary from 100 mGy to 1,300 mGy if exposed to non-collimated fields and from 20 mGy to 160 mGy for collimated, moving fields. The lifetime risk of developing brain cancer was estimated to be increased by 2% to 80% as a result of the exposure. Given the very small lifetime background risk of brain tumor, the excess number of cases will be small even though the relative increase might be as high as 80%. ALARA principles of collimation and dose optimization are the most effective means to minimize the risk of future radiation-related cancer. (orig.)

Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

International Nuclear Information System (INIS)

Shueng, Pei-Wei; Lin, Shih-Chiang; Chang, Hou-Tai; Chong, Ngot-Swan; Chen, Yu-Jen; Wang, Li-Ying; Hsieh, Yen-Ping; Hsieh, Chen-Hsi

2009-01-01

The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy

Health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques: a case study with rice farmers in Vietnam.

Science.gov (United States)

Phung, Dung Tri; Connell, Des; Yu, Qiming; Chu, Cordia

2013-09-01

Various methods for risk characterization have been developed using probabilistic approaches. Data on Vietnamese farmers are available for the comparison of outcomes for risk characterization using different probabilistic methods. This article addresses the health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques obtained from a case study with rice farmers in Vietnam. Urine samples were collected from farmers and analyzed for trichloropyridinol (TCP), which was converted into absorbed daily dose of chlorpyrifos. Adverse health response doses due to chlorpyrifos exposure were collected from epidemiological studies to develop dose-adverse health response relationships. The health risk of chlorpyrifos was quantified using hazard quotient (HQ), Monte Carlo simulation (MCS), and overall risk probability (ORP) methods. With baseline (prior to pesticide spraying) and lifetime exposure levels (over a lifetime of pesticide spraying events), the HQ ranged from 0.06 to 7.1. The MCS method indicated less than 0.05% of the population would be affected while the ORP method indicated that less than 1.5% of the population would be adversely affected. With postapplication exposure levels, the HQ ranged from 1 to 32.5. The risk calculated by the MCS method was that 29% of the population would be affected, and the risk calculated by ORP method was 33%. The MCS and ORP methods have advantages in risk characterization due to use of the full distribution of data exposure as well as dose response, whereas HQ methods only used the exposure data distribution. These evaluations indicated that single-event spraying is likely to have adverse effects on Vietnamese rice farmers. © 2013 Society for Risk Analysis.

Effective dose and cancer risk in PET/CT exams; Dose efetiva e risco de cancer em exames de PET/CT

Energy Technology Data Exchange (ETDEWEB)

Pinto, Gabriella M.; Sa, Lidia Vasconcellos de, E-mail: montezano@ird.gov.br, E-mail: Iidia@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2013-07-01

Due to the use of radiopharmaceutical positron-emitting in PET exam and realization of tomography by x-ray transmission in CT examination, an increase of dose with hybrid PET/CT technology is expected. However, differences of doses have been reported in many countries for the same type of procedure. It is expected that the dose is an influent parameter to standardize the protocols of PET/CT. This study aimed to estimate the effective doses and absorbed in 65 patients submitted to oncological Protocol in a nuclear medicine clinic in Rio de Janeiro, considering the risk of induction of cancer from the scan. The CT exam-related doses were estimated with a simulator of PMMA and simulated on the lmPACT resistance, which for program effective dose, were considered the weight factors of the lCRP 103. The PET exam doses were estimated by multiplying the activity administered to the patient with the ICRP dose 80 factors. The radiological risk for cancer incidence were estimated according to the ICRP 103. The results showed that the effective dose from CT exam is responsible for 70% of the effective total in a PET/CT scan. values of effective dose for the PET/CT exam reached average values of up to 25 mSv leading to a risk of 2, 57 x 10{sup -4}. Considering that in staging of oncological diseases at least four tests are performed annually, the total risk comes to 1,03x 10{sup -3}.

Non-Linear Relationship between Economic Growth and CO₂ Emissions in China: An Empirical Study Based on Panel Smooth Transition Regression Models.

Science.gov (United States)

Wang, Zheng-Xin; Hao, Peng; Yao, Pei-Yi

2017-12-13

The non-linear relationship between provincial economic growth and carbon emissions is investigated by using panel smooth transition regression (PSTR) models. The research indicates that, on the condition of separately taking Gross Domestic Product per capita (GDPpc), energy structure (Es), and urbanisation level (Ul) as transition variables, three models all reject the null hypothesis of a linear relationship, i.e., a non-linear relationship exists. The results show that the three models all contain only one transition function but different numbers of location parameters. The model taking GDPpc as the transition variable has two location parameters, while the other two models separately considering Es and Ul as the transition variables both contain one location parameter. The three models applied in the study all favourably describe the non-linear relationship between economic growth and CO₂ emissions in China. It also can be seen that the conversion rate of the influence of Ul on per capita CO₂ emissions is significantly higher than those of GDPpc and Es on per capita CO₂ emissions.

Soy food intake and risk of gastric cancer: A dose-response meta-analysis of prospective studies.

Science.gov (United States)

Weng, Ke-Gui; Yuan, Ya-Ling

2017-08-01

Epidemiological studies were inconsistent on the association between soy food intake and risk of gastric cancer (GC). This study aimed to determine the role of soy food intake in the development of GC.A systematic search was conducted in PubMed and Web of Science to identify all relevant studies. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model, and the dose-response relationship between soy food intake and GC risk was also assessed.Thirteen prospective studies were identified with a total of 517,106 participants and 5800 cases. Among 11 types of soy food, high intake of total soy food (the highest vs the lowest category: RR: 0.78, 95% CI: 0.62-0.98) and nonfermented soy food (RR: 0.63, 95% CI: 0.50-0.79) were inversely associated with GC risk, while high intake of miso soup was associated with the risk in male (RR: 1.17, 95% CI: 1.02-1.36). In dose-response meta-analysis, total soy food intake (0-150 g/day) showed no significant association with GC risk, while high intake of nonfermented soy food was inversely related, especially an intake of more than 100 g/day. In male, miso soup intake (1-5 cups/day) was significantly associated with GC risk.High intake of nonfermented soy food might reduce the risk of GC, while miso soup intake might increase the risk in male.

Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia

International Nuclear Information System (INIS)

Kempen-Harteveld, M. Loes van; Belkacemi, Yazid; Kal, Henk B.; Labopin, Myriam; Frassoni, Francesco

2002-01-01

Purpose: To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, α/β, and the rate of repair of sublethal damage, μ value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. Methods and Materials: The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for α/β and μ were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, α/β and μ values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of α/β and μ values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. Results: The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was

Low doses of ionizing radiation: Relationship between biological benefit and damage induction. A synopsis

International Nuclear Information System (INIS)

Feinendegen, L.E.

2005-01-01

damage at high doses but protection at low doses. This low-dose induced protection mainly functions against accumulation of DNA damage from endogenous sources, such as ROS. Bystander effects from high-dosed cells to non-irradiated neighboring cells appear to induce both damage and protection. With respect to oncogenesis, a model using microdosimetry and based on the above dual response pattern at low doses and dose rates is consistent with published non-linear epidemiological and experimental data and, thus, contradicts the linear-no-threshold dose-risk hypothesis for radiation induced cancer. The LNT hypothesis should be abandoned and be replaced by a hypothesis that is scientifically justified and causes less unreasonable fear and unnecessary expenditure. (author)

Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.

Science.gov (United States)

Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola

2014-10-15

Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A recalculation of the age dependent dose-effect-relationship of the life span study of Hiroshima and Nagasaki

International Nuclear Information System (INIS)

Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

1996-01-01

The basis of the presented model is the multistage process of carcinogenesis as a biological effect. It provides simultaneously the age-dependent mortality of spontaneous and radiation induced solid tumors and dose-effect relationships at any age after exposure. The model has been used to describe the solid cancer mortality rates of the atomic bomb survivors of Hiroshima and Nagasaki. It has characteristics of both relative and absolute risk projections depending on the age of exposure. (author)

Thyroid doses and risk to paediatric patients undergoing neck CT examinations

Energy Technology Data Exchange (ETDEWEB)

Spampinato, Maria Vittoria; Tipnis, Sameer; Huda, Walter [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Tavernier, Joshua [Medical University of South Carolina, College of Medicine, Charleston, SC (United States)

2015-07-15

To estimate thyroid doses and cancer risk for paediatric patients undergoing neck computed tomography (CT). We used average CTDI{sub vol} (mGy) values from 75 paediatric neck CT examinations to estimate thyroid dose in a mathematical anthropomorphic phantom (ImPACT Patient CT Dosimetry Calculator). Patient dose was estimated by modelling the neck as mass equivalent water cylinder. A patient size correction factor was obtained using published relative dose data as a function of water cylinder size. Additional correction factors included scan length and radiation intensity variation secondary to tube-current modulation. The mean water cylinder diameter that modelled the neck was 14 ± 3.5 cm. The mathematical anthropomorphic phantom has a 16.5-cm neck, and for a constant CT exposure, would have thyroid doses that are 13-17 % lower than the average paediatric patient. CTDI{sub vol} was independent of age and sex. The average thyroid doses were 31 ± 18 mGy (males) and 34 ± 15 mGy (females). Thyroid cancer incidence risk was highest for infant females (0.2 %), lowest for teenage males (0.01 %). Estimated absorbed thyroid doses in paediatric neck CT did not significantly vary with age and gender. However, the corresponding thyroid cancer risk is determined by gender and age. (orig.)

The time factor in dose-effect relationships

International Nuclear Information System (INIS)

Jones, H.B.; Grendon, A.; White, M.R.; California Univ., Berkeley

1976-01-01

The assumption that carcinogenic risk is proportional to dose fails to consider that probable time of actual cancer incidence. The time lag between exposure and carcinogenic effect for radiation and chemical agents varies as Dosesup(-1/n), with napproximately3. A model is offered explaining that concentration of initially altered cells depends on dose, whereas their chance for development into tumours on their proximity, which varies as Dsup(-1/3). Because of biological variability, n has a range of values. The model implies that tumours resulting from a single exposure should be closely distributed in time, producing a pulse of cases and subsequently being essentially without effect. Testing of the Dsup(-1/3) rule was extended and its model, by further refinement of methods, applied to radiogenic leukaemia risk and to the effect of urethan in inducing lung tumours in mice with and without radiation exposure as a possible cocarcinogen. Radiation did not affect the tumour yield from urethan in mice. Radiogenic leukaemia and lung tumours induced by urethan both occur in proportion to exposure, but the time of their occurrence is limited to a short interval in relation to life span. Similarly, in murine or in human radiogenic leukaemia, leukaemia risk occurs in proportion to exposure, but the time of occurrences is limited to a short interval in relation to life span. In both sets of observations, as well as in other test systems of carcinogenesis, the peak of occurrence or the mean latent period is roughly inversely related to Dsup(-1/3). Applied to lung tumours and leukaemia, the spread of cases about the peak incidence was found to be typically less than a fifth of the life span. Exposure risks do not continue to act over life span. Neoplastic disease risk from carcinogens levels too low to be tested experimentally, theoretically usually lies beyond the life span. The social and economic consequences of a theoretically calculated number of deaths due to those

Radiation Dose Risk and Diagnostic Benefit in Imaging Investigations

OpenAIRE

Dobrescu, Lidia; Rădulescu, Gheorghe-Cristian

2015-01-01

The paper presents many facets of medical imaging investigations radiological risks. The total volume of prescribed medical investigations proves a serious lack in monitoring and tracking of the cumulative radiation doses in many health services. Modern radiological investigations equipment is continuously reducing the total dose of radiation due to improved technologies, so a decrease in per caput dose can be noticed, but the increasing number of investigations has determined a net increase ...

Towards a new dose and dose-rate effectiveness factor (DDREF)? Some comments.

Science.gov (United States)

Chadwick, K H

2017-06-26

The aim of this article is to offer a broader, mechanism-based, analytical tool than that used by (Rühm et al 2016 Ann. ICRP 45 262-79) for the interpretation of cancer induction relationships. The article explains the limitations of this broader analytical tool and the implications of its use in view of the publications by Leuraud et al 2015 (Lancet Haematol. 2 e276-81) and Richardson et al 2015 (Br. Med. J. 351 h5359). The publication by Rühm et al 2016 (Ann. ICRP 45 262-79), which is clearly work in progress, reviews the current status of the dose and dose-rate effectiveness factor (DDREF) as recommended by the ICRP. It also considers the issues which might influence a reassessment of both the value of the DDREF as well as its application in radiological protection. In this article, the problem is approached from a different perspective and starts by commenting on the limited scientific data used by Rühm et al 2016 (Ann. ICRP 45 262-79) to develop their analysis which ultimately leads them to use a linear-quadratic dose effect relationship to fit solid cancer mortality data from the Japanese life span study of atomic bomb survivors. The approach taken here includes more data on the induction of DNA double strand breaks and, using experimental data taken from the literature, directly relates the breaks to cell killing, chromosomal aberrations and somatic mutations. The relationships are expanded to describe the induction of cancer as arising from radiation induced cytological damage coupled to cell killing since the cancer mutated cell has to survive to express its malignant nature. Equations are derived for the induction of cancer after both acute and chronic exposure to sparsely ionising radiation. The equations are fitted to the induction of cancer in mice to illustrate a dose effect relationship over the total dose range. The 'DDREF' derived from the two equations varies with dose and the DDREF concept is called into question. Although the equation for

Nonlinear model of high-dose implantation

International Nuclear Information System (INIS)

Danilyuk, A.

2001-01-01

The models of high-dose implantation, using the distribution functions, are relatively simple. However, they must take into account the variation of the function of distribution of the implanted ions with increasing dose [1-4]. This variation takes place owing to the fact that the increase of the concentration of the implanted ions results in a change of the properties of the target. High-dose implantation is accompanied by sputtering, volume growth, diffusion, generation of defects, formation of new phases, etc. The variation of the distribution function is determined by many factors and is not known in advance. The variation within the framework of these models [1-4] is taken into account in advance by the introduction of intuitive assumptions on the basis of implicit considerations. Therefore, these attempts should be regarded as incorrect. The model prepared here makes it possible to take into account the sputtering of the target, volume growth and additional declaration on the implanted ions. Without any assumptions in relation to the variation of the distribution function with increasing dose. In our model it is assumed that the type of distribution function for small doses in a pure target substance is the same as in substances with implanted ions. A second assumption relates to the type of the distribution function valid for small doses in the given substances. These functions are determined as a result of a large number of theoretical and experimental investigations and are well-known at the present time. They include the symmetric and nonsymmetric Gauss distribution, the Pearson distribution, and others. We examine implantation with small doses of up to 10 14 - 10 15 cm -2 when the accurately known distribution is valid

Estimated risk for secondary cancer in the contra-lateral breast following radiation therapy of breast cancer

International Nuclear Information System (INIS)

Johansen, Safora; Danielsen, Turi; Olsen, Dag Rune

2008-01-01

Purpose. To facilitate a discussion about the impact of dose heterogeneity on the risk for secondary contralateral breast (CB) cancer predicted with linear and non linear models associated with primary breast irradiation. Methods and materials. Dose volume statistics of the CB calculated for eight patients using a collapsed cone algorithm were used to predict the excess relative risk (ERR) for cancer induction in CB. Both linear and non-linear models were employed. A sensitivity analysis demonstrating the impact of different parameter values on calculated ERR for the eight patients was also included in this study. Results. A proportionality assumption was established to make the calculations with a linear and non-linear model comparable. ERR of secondary cancer predicted by the linear model varied considerably between the patients, while the predicted ERR for the same patients using the non-linear model showed very small variation. The predicted ERRs by the two models were indistinguishable for small doses, i.e. below ∼3 Gy. The sensitivity analysis showed that the quadratic component of the radiation-induction pre-malignant cell term is negligible for lower dose level. The ERR is highly sensitive to the value of agr1 and agr2. Conclusions. Optimization of breast cancer radiation therapy, where also the risk for radiation induced secondary malignancies in the contralateral breast is taken into account, requires robust and valid risk assessment. The linear dose-risk model does not account for the complexity in the mechanisms underlying the development of secondary malignancies following exposure to radiation; this is particularly important when estimating risk associated with highly heterogeneous dose distributions as is the case in the contralateral breast of women receiving breast cancer irradiation

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer.

Science.gov (United States)

de Vathaire, Florent; Haddy, Nadia; Allodji, Rodrigue S; Hawkins, Mike; Guibout, Catherine; El-Fayech, Chiraz; Teinturier, Cécile; Oberlin, Odile; Pacquement, Hélène; Diop, Fara; Kalhouche, Amar; Benadjaoud, Mohamedamine; Winter, David; Jackson, Angela; Bezin Mai-Quynh, Giao; Benabdennebi, Aymen; Llanas, Damien; Veres, Cristina; Munzer, Martine; Nguyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Deutsch, Eric; Lefkopoulos, Dimitri; Schlumberger, Martin; Diallo, Ibrahima; Rubino, Carole

2015-11-01

Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation. This study aimed to investigate the role of potential modifiers of the dose response. We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1). Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.

Low dose diagnostic radiation does not increase cancer risk in cancer prone mice

Energy Technology Data Exchange (ETDEWEB)

Boreham, D., E-mail: dboreham@nosm.ca [Northern Ontario School of Medicine, ON (Canada); Phan, N., E-mail: nghiphan13@yahoo.com [Univ. of Ottawa, Ottawa, ON (Canada); Lemon, J., E-mail: lemonja@mcmaster.ca [McMaster Univ., Hamilton, ON (Canada)

2014-07-01

The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten consecutive weeks adding an additional radiation burden of 0.1 Gy. Short-term biological responses and subsequent lifetime cancer risk were investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower constitutive levels of oxidative DNA damage and cell death (apoptosis), compared to non-CT scanned mice. This shows that multiple low dose radiation exposures modified the radio response and indicates protective processes were induced in mice. In mice treated with the multiple CT scans following the high cancer-inducing 4 Gy dose, tumour latency was increased, significantly prolonging lifespan. We conclude that repeated CT scans can reduce the cancer risk of a prior high-dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in Trp53+/-mice. This research shows for the first time that low dose exposure long after cancer initiation events alter risk and reduce cancer morbidity. Cancer induction following low doses does not follow a linear non-threshold model of risk and this model should not be used to extrapolate risk to humans following low dose exposure to ionizing radiation. (author)

Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Kanemoto, Ayae

2013-01-01

Background: Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT). Material and methods: The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients' characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography. Results. Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p ≥ 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy 3 (RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy 3 ] and the AUCs of V30 to V120 (EQD2; 18-72 Gy 3 ) and D max to D 1 0 cm 3 were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture. Conclusion. DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and D max to D 1 0 cm 3 were also significant and clinically useful for estimating the risk of rib fracture after hypofractionated PBT

Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Kanemoto, Ayae [Proton Medical Research Center and Dept. of Radiation Oncology, Univ. of Tsukuba, Ibaraki (Japan)], e-mail: ayaek@pmrc.tsukuba.ac.jp [and others

2013-04-15

Background: Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT). Material and methods: The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients' characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography. Results. Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p {>=} 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy{sub 3} (RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy{sub 3}] and the AUCs of V30 to V120 (EQD2; 18-72 Gy{sub 3}) and D{sub max} to D{sub 1}0{sub cm}{sup 3} were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture. Conclusion. DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and D{sub max} to D{sub 1}0{sub cm}{sup 3} were also significant and clinically useful for estimating

Evaluation of effective dose and excess lifetime cancer risk from ...

African Journals Online (AJOL)

Evaluation of effective dose and excess lifetime cancer risk from indoor and outdoor gamma dose rate of university of Port Harcourt Teaching Hospital, Rivers State. ... Therefore, the management of University of Port Harcourt teaching hospital ...

Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

Science.gov (United States)

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

2017-08-17

To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis.

Science.gov (United States)

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Sciacca, Salvatore; Pajak, Andrzej; Martínez-González, Miguel A; Giovannucci, Edward L; Galvano, Fabio

2016-12-01

Coffee consumption has been associated with several benefits toward human health. However, its association with mortality risk has yielded contrasting results, including a non-linear relation to all-cause and cardiovascular disease (CVD) mortality and no association with cancer mortality. As smoking habits may affect the association between coffee and health outcomes, the aim of the present study was to update the latest dose-response meta-analysis of prospective cohort studies on the association between coffee consumption and mortality risk and conduct stratified analyses by smoking status and other potential confounders. A systematic search was conducted in electronic databases to identify relevant studies, risk estimates were retrieved from the studies, and dose-response analysis was modeled by using restricted cubic splines. A total of 31 studies comprising 1610,543 individuals and 183,991 cases of all-cause, 34,574 of CVD, and 40,991 of cancer deaths were selected. Analysis showed decreased all-cause [relative risk (RR) = 0.86, 95 % confidence interval (CI) = 0.82, 0.89)] and CVD mortality risk (RR = 0.85, 95 % CI = 0.77, 0.93) for consumption of up to 4 cups/day of coffee, while higher intakes were associated with no further lower risk. When analyses were restricted only to non-smokers, a linear decreased risk of all-cause (RR = 0.94, 95 % CI = 0.93, 0.96), CVD (RR = 0.94, 95 % CI = 0.91, 0.97), and cancer mortality (RR = 0.98, 95 % CI = 0.96, 1.00) for 1 cup/day increase was found. The search for other potential confounders, including dose-response analyses in subgroups by gender, geographical area, year of publication, and type of coffee, showed no relevant differences between strata. In conclusion, coffee consumption is associated with decreased risk of mortality from all-cause, CVD, and cancer; however, smoking modifies the observed risk when studying the role of coffee on human health.

Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis

International Nuclear Information System (INIS)

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Sciacca, Salvatore; Pajak, Andrzej; Martínez-González, Miguel A.; Giovannucci, Edward L.; Galvano, Fabio

2016-01-01

Coffee consumption has been associated with several benefits toward human health. However, its association with mortality risk has yielded contrasting results, including a non-linear relation to all-cause and cardiovascular disease (CVD) mortality and no association with cancer mortality. As smoking habits may affect the association between coffee and health outcomes, the aim of the present study was to update the latest dose-response meta-analysis of prospective cohort studies on the association between coffee consumption and mortality risk and conduct stratified analyses by smoking status and other potential confounders. A systematic search was conducted in electronic databases to identify relevant studies, risk estimates were retrieved from the studies, and dose-response analysis was modeled by using restricted cubic splines. A total of 31 studies comprising 1610,543 individuals and 183,991 cases of all-cause, 34,574 of CVD, and 40,991 of cancer deaths were selected. Analysis showed decreased all-cause [relative risk (RR) = 0.86, 95 % confidence interval (CI) = 0.82, 0.89)] and CVD mortality risk (RR = 0.85, 95 % CI = 0.77, 0.93) for consumption of up to 4 cups/day of coffee, while higher intakes were associated with no further lower risk. When analyses were restricted only to non-smokers, a linear decreased risk of all-cause (RR = 0.94, 95 % CI = 0.93, 0.96), CVD (RR = 0.94, 95 % CI = 0.91, 0.97), and cancer mortality (RR = 0.98, 95 % CI = 0.96, 1.00) for 1 cup/day increase was found. The search for other potential confounders, including dose-response analyses in subgroups by gender, geographical area, year of publication, and type of coffee, showed no relevant differences between strata. In conclusion, coffee consumption is associated with decreased risk of mortality from all-cause, CVD, and cancer; however, smoking modifies the observed risk when studying the role of coffee on human health.

Generation of dose-response relationships to assess the effects of acidity in precipitation on growth and productivity of vegetation

International Nuclear Information System (INIS)

Evans, L.S.

1981-01-01

Experiments were performed with several plant species in natural environments as well in a greenhouse and/or tissue culture facilities to establish dose-response functions of plant responses to simulated acidic rain in order to determine environmental risk assessments to ambient levels of acidic rain. Response functions of foliar injury, biomass of leaves and seed of soybean and pinto beans, root yields of radishes and garden beets, and reproduction of bracken fern are considered. The dose-response function of soybean seed yields with the hydrogen ion concentration of simulated acidic rainfalls was expressed by the equation y = 21.06-1.01 log x where y = seed yield in grams per plant and x = the hydrogen concentration if μeq l -1 . The correlation coefficient of this relationship was -0.90. A similar dose-response function was generated for percent fertilization of ferns in a forest understory. When percent fertilization is plotted on logarithmic scale with hydrogen ion concentration of the simulated rain solution, the Y intercept is 51.18, slope -0.041 with a correlation coefficient of -0.98. Other dose-response functions were generated that assist in a general knowledge as to which plant species and which physiological processes are most impacted by acidic precipitation. Some responses did not produce convenient dose-response relationships. In such cases the responses may be altered by other environmental factors or there may be no differences among treatment means

Concomitant chemo-radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after cancer in childhood: a case control study

International Nuclear Information System (INIS)

Guerin, S.; Guibout, C.; Vathaire, F. de; Shamsaldin, A.; Diallo, I.; Oberlin, O.; Hartmann, O.; Le Deley, M.C.; Dondon, M.G.; Hawkins, M.

2006-01-01

Radiotherapy and chemotherapy are associated with an increased risk of a second malignant neoplasm. after a cancer during childhood. This study specified the dose effect relationship between the local dose of radiation received at the site of the second malignant neoplasm and the risk of a second malignant neoplasm.It also investigated the effect of chemo radiotherapy on the risk of second malignant neoplasm. An European cohort of 4581 patients, treated for a solid cancer during childhood have been included in the study. 153 cases with a second malignant neoplasm, and 442 controls were matched according to sex, age at first cancer, calendar year, type of first cancer and follow-up. The local dose of radiation was estimated at the site of the second malignant neoplasm, for each case and at the same site, for his matched control. In conclusion, radiation was the foremost treatment related risk factor for the occurrence of a second malignant neoplasm. Compared to sequential treatment, concomitant chemo radiotherapy may lead to a higher risk of a second malignant neoplasm. (N.C.)

Radiation dose and second cancer risk in patients treated for cancer of the cervix

International Nuclear Information System (INIS)

Boice, J.D. Jr.; Engholm, G.; Kleinerman, R.A.

1988-01-01

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors

The relationship between liquidity risk and credit risk in Islamic banking industry of Iran

Directory of Open Access Journals (Sweden)

Hashem Nikomaram

2013-04-01

Full Text Available An integrated risk management is a process, which enables banks to measure and manage all risks, simultaneously. The recent turbulent chaos on banking industry has increase the relative importance of risk management, more than before. This paper investigates the relationship between credit risk and liquidity risk among Iranian banks. The proposed study includes all private and governmental banks as population over the period 2005-2012. The results Pearson correlation has disclosed a positive and meaningful relationship between credit and liquidity risks. Bank size also impacts on two mentioned risk factors but we there seems to be no relationship between financial chaos and type of ownership with risk factors.

Nonlinear Uncertainty Propagation of Satellite State Error for Tracking and Conjunction Risk Assessment

Science.gov (United States)

2017-12-18

AFRL-RV-PS- AFRL-RV-PS- TR-2017-0177 TR-2017-0177 NONLINEAR UNCERTAINTY PROPAGATION OF SATELLITE STATE ERROR FOR TRACKING AND CONJUNCTION RISK...Uncertainty Propagation of Satellite State Error for Tracking and Conjunction Risk Assessment 5a. CONTRACT NUMBER FA9453-16-1-0084 5b. GRANT NUMBER...prediction and satellite conjunction analysis. Statistical approach utilizes novel methods to build better uncertainty state characterization in the context

Equivalent dose, effective dose and risk assessment from cephalometric radiography to critical organs

International Nuclear Information System (INIS)

Kang, Seong Sook; Cho, Bon Hae; Kim, Hyun Ja

1995-01-01

In head and neck region, the critical organ and tissue doses were determined, and the risks were estimated from lateral, posteroanterial and basilar cephalometric radiography. For each cephalometric radiography, 31 TLDs were placed in selected sites (18 internal and 13 external sites) in a tissue-equivalent phantom and exposed, then read-out in the TLD reader. The following results were obtained; 1. From lateral cephalometric radiography, the highest effective dose recorded was that delivered to the salivary gland (3.6 μSv) and the next highest dose was that received by the bone marrow (3 μSv). 2. From posteroanterial cephalometric radiography, the highest effective dose recorded was that delivered to the salivary gland (2 μSv) and the next highest dose was that received by the bone marrow (1.8 μSv). 3. From basilar cephalometric radiography, the highest effective dose recorded was that delivered to the thyroid gland (31.4 μSv) and the next highest dose was that received by the salivary gland (13.3 μSv). 4. The probabilities of stochastic effect from lateral, posteroanterial and basilar cephalometric radiography were 0.72 X 10 -6 , 0.49 X 10 -6 and 3.51 X 10 -6 , respectively.

Dose effect relationships for radiation induced cancer: relevance of animal evidence

International Nuclear Information System (INIS)

Coggle, J.E.

1982-01-01

This article is based upon a paper which was presented at the SRP meeting on the Biological Bases of Radiation Protection Standards, October 1981. It is suggested that experimental radiation carcinogenesis data derived from animal studies will probably never provide numerical evidence of risk that is applicable to man. The uncertainties involved in any extrapolation of risk estimates from mice to men surely outweigh the uncertainties in the human epidemiological data. It is also suggested that at least in the foreseeable future animal data will not solve the perennial problem of the shape at low doses of the dose response curve for radiogenic cancer. At most the data may clarify the debate over linearity-non linearity and over the existence or otherwise of a threshold. However, the paper does suggest a very positive role for animal data in providing semi-quantitative generalisations for radiological protection concerning such variables as dose rate, radiation quality, partial body/organ exposure and in situations where the dose is received in a highly inhomogeneous fashion, e.g. the special problems of internal emitters. (author)

Radiation dose and subsequent risk for stomach cancer in long-term survivors of cervical cancer

DEFF Research Database (Denmark)

Kleinerman, Ruth A; Smith, Susan A; Holowaty, Eric

2013-01-01

To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer.......To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer....

Internal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer.

Science.gov (United States)

Thor, Maria; Owosho, Adepitan A; Clark, Haley D; Oh, Jung Hun; Riaz, Nadeem; Hovan, Allan; Tsai, Jillian; Thomas, Steven D; Yom, Sae Hee K; Wu, Jonn S; Huryn, Joseph M; Moiseenko, Vitali; Lee, Nancy Y; Estilo, Cherry L; Deasy, Joseph O

2017-02-01

To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. Objective xerostomia was assessed in 121 patients (n Cohort1 =55; n Cohort2 =66) treated to 70Gy@2Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (p HL )). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean contra , Dmean ipsi ) were estimated from the generated dose-response curves. The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmean contra and Dmean ipsi (Cohort1: 0.17·Dmean contra +0.11·Dmean ipsi -8.13; AUC=0.90±0.05; p=0.0002±0.002; p HL =0.22±0.23; Cohort2: AUC=0.81; pxerostomia following IMRT. Our results also suggest decreasing Dmean contra to below 20Gy, while keeping Dmean ipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Radiation exposure and risk of death

International Nuclear Information System (INIS)

Hongo, Syozo

1979-01-01

By using the risk factor given in ICRP publication 26 and an assumption of linear relationship between risk and dose, death rate and death number which correspond to radiation dose level and collective dose level of Japanese are estimated and they are compared with vital statistics of Japanese in 1975 to get out some ideas about radiation risk relative to the risks of everyday life. (author)

High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer

Directory of Open Access Journals (Sweden)

Keisei Okamoto

2017-02-01

Full Text Available Purpose : To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR brachytherapy in combination with external beam radiotherapy (EBRT and short-term androgen deprivation therapy (ADT. Material and methods : From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT. The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%, 61 patients with 2 high-risk factors (43%, and 22 patients with 3 high-risk factors (15% including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. Results : Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS rate of 97.2%, and an overall survival (OS rate of 95.5%. Conclusions : High-dose (BED ≥ 220 Gy radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further.

Risk-return relationship in a complex adaptive system.

Directory of Open Access Journals (Sweden)

Kunyu Song

Full Text Available For survival and development, autonomous agents in complex adaptive systems involving the human society must compete against or collaborate with others for sharing limited resources or wealth, by using different methods. One method is to invest, in order to obtain payoffs with risk. It is a common belief that investments with a positive risk-return relationship (namely, high risk high return and vice versa are dominant over those with a negative risk-return relationship (i.e., high risk low return and vice versa in the human society; the belief has a notable impact on daily investing activities of investors. Here we investigate the risk-return relationship in a model complex adaptive system, in order to study the effect of both market efficiency and closeness that exist in the human society and play an important role in helping to establish traditional finance/economics theories. We conduct a series of computer-aided human experiments, and also perform agent-based simulations and theoretical analysis to confirm the experimental observations and reveal the underlying mechanism. We report that investments with a negative risk-return relationship have dominance over those with a positive risk-return relationship instead in such a complex adaptive systems. We formulate the dynamical process for the system's evolution, which helps to discover the different role of identical and heterogeneous preferences. This work might be valuable not only to complexity science, but also to finance and economics, to management and social science, and to physics.

Risk-return relationship in a complex adaptive system.

Science.gov (United States)

Song, Kunyu; An, Kenan; Yang, Guang; Huang, Jiping

2012-01-01

For survival and development, autonomous agents in complex adaptive systems involving the human society must compete against or collaborate with others for sharing limited resources or wealth, by using different methods. One method is to invest, in order to obtain payoffs with risk. It is a common belief that investments with a positive risk-return relationship (namely, high risk high return and vice versa) are dominant over those with a negative risk-return relationship (i.e., high risk low return and vice versa) in the human society; the belief has a notable impact on daily investing activities of investors. Here we investigate the risk-return relationship in a model complex adaptive system, in order to study the effect of both market efficiency and closeness that exist in the human society and play an important role in helping to establish traditional finance/economics theories. We conduct a series of computer-aided human experiments, and also perform agent-based simulations and theoretical analysis to confirm the experimental observations and reveal the underlying mechanism. We report that investments with a negative risk-return relationship have dominance over those with a positive risk-return relationship instead in such a complex adaptive systems. We formulate the dynamical process for the system's evolution, which helps to discover the different role of identical and heterogeneous preferences. This work might be valuable not only to complexity science, but also to finance and economics, to management and social science, and to physics.

Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

Science.gov (United States)

Godos, Justyna; Micek, Agnieszka; Marranzano, Marina; Salomone, Federico; Rio, Daniele Del; Ray, Sumantra

2017-08-28

A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.

Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

Science.gov (United States)

Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

2016-04-15

While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer. © 2015 UICC.

Collective effective dose equivalent, population doses and risk estimates from occupational exposures in Japan

International Nuclear Information System (INIS)

Maruyama, Takashi; Nishizawa, Kanae; Kumamoto, Yoshikazu; Iwai, Kazuo; Mase, Naomichi.

1993-01-01

Collective dose equivalent and population dose from occupational exposures in Japan, 1988 were estimated on the basis of a nationwide survey. The survey was conducted on annual collective dose equivalents by sex, age group and type of radiation work for about 0.21 million workers except for the workers in nuclear power stations. The data on the workers in nuclear power stations were obtained from the official report of the Japan Nuclear Safety Commission. The total number of workers including nuclear power stations was estimated to be about 0.26 million. Radiation works were subdivided as follows: medical works including dental; non-atomic energy industry; research and education; atomic energy industry and nuclear power station. For the determination of effective dose equivalent and population dose, organ or tissue doses were measured with a phantom experiment. The resultant doses were compared with the doses previously calculated using a chord length technique and with data from ICRP publications. The annual collective effective dose equivalent were estimated to be about 21.94 person·Sv for medical workers, 7.73 person·Sv for industrial workers, 0.75 person·Sv for research and educational workers, 2.48 person·Sv for atomic energy industry and 84.4 person ·Sv for workers in nuclear power station. The population doses were calculated to be about 1.07 Sv for genetically significant dose, 0.89 Sv for leukemia significant dose and 0.42 Sv for malignant significant dose. The population risks were estimated using these population doses. (author)

Application and inspiration of risk control in dose control in Fukushima nuclear accident

International Nuclear Information System (INIS)

Yu Shaoqing; Chen Yan; Chai Jianshe; Zhang Chunming

2013-01-01

The article introduced the basic concept of risk and risk control methods. Using the risk control methods, we analyzed and evaluated the actions to control dose of public and occupational radiation exposure in the Fukushima Dai-ichi nuclear power plant accident, especially found out the weak points of these actions, and finally discussed the application of the risk control methods in dose management during nuclear accidents. (authors)

Chronic periodontitis and smoking. Prevalence and dose-response relationship.

Science.gov (United States)

Khan, Shahrukh; Khalid, Taimur; Awan, Kamran H

2016-08-01

To determine the prevalence and dose-response relationship of chronic periodontitis among smokers in Pakistan.   This is a cross-sectional study among participants seeking dental care in Karachi Medical and Dental College, Karachi, Pakistan. A total of 443 participants with a mean age of 44.3 (±6.5) participated in the study from April 2011 to December 2011. Males comprised 64.7%, and females comprised 35.2%. Participants were interviewed on social demographics and oral habits. Participants with shallow pockets (3.5-5.5 mm) and deep pockets (greater than 5.5 mm) were considered suffering from chronic periodontitis. The characteristics of participants were assessed using frequency distribution for categorical variables and mean (standard deviation) for continuous variables.  Among 443 participants, smokers were distributed as 55.1% and non-smokers as 44.9%. Smoking was found to be significantly related to young adults (p less than 0.007), male gender (p less than 0.001), and lower education level (p less than 0.01). Overall prevalence of chronic periodontitis among smokers was estimated at 81.6%. Heavy smoking was found to have significantly high prevalence (p less than 0.001) and severity (p less than 0.001) of periodontitis as compared with moderate and light smokers. The multivariate unadjusted model depicted 3.5 times higher risk of chronic periodontitis among smokers (p less than 0.001). Chronic periodontitis had a high prevalence among smokers. Heavy smoking was found to have a higher risk for having periodontitis.

On the genetic risk after high dose radioiodine therapy with regard to the gonadal dose

International Nuclear Information System (INIS)

Ehrenheim, C.; Hauswirth, C.; Fitschen, J.; Martin, E.; Oetting, G.; Hundeshagen, H.

1997-01-01

Aim: The genetic risk for the offspring of patients treated with high doses of radioiodine was to be assessed with special regard to the gonadal dose caused by diagnostic and therapeutic procedures. Methods: 41 young females (aged between 19 and 39 years) and four young males (aged 26 to 36 years) treated with radioiodine because of a thyroid carcinoma were interviewed by use of a questionnaire. The course of pregnancy and birth history could be documented as well as the congenital and developmental conditions of 56 children. Results: The amount of radioactivity applied for therapy and whole body scans ranged over 4,144 and 35,15 GBq I-131; the individual gonadal dose was calculated based on the MIRD model and ranged over 0,2 and 2,2 Sv (0,51 Sv at a mean). The period of time between the last radioiodine application and confinement was at least 9 months, not exceeding 14 years. As to the course of pregnancy and birth two early abortions, one extrauterine gravidity and one premature birth due to an insufficiency of the placenta were stated. In one case a chromosomal translocation 7/14 occured as a genetic defect which lead to an interruption. The children's development was unconspicuous except of two cases of neurodermatitis as well as multiple allergies and an early closure of the anterior fontanelle in one child each. Conclusion: Although the genetic risk is supposed to increase with the gonadal dose achieved (doubling dose 1 Sv) and the increased risk of any congenital anomaly was calculated as about 13% at a mean in our patients, the rate of genetic determined diseases was not elevated (1,8% or 1/57). Thus, no increase of genetic defects or congenital malformations was reported in a total of 408 children described in the literature and in our group. (orig.) [de

Single toxin dose-response models revisited

Energy Technology Data Exchange (ETDEWEB)

Demidenko, Eugene, E-mail: eugened@dartmouth.edu [Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH03756 (United States); Glaholt, SP, E-mail: sglaholt@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States); Kyker-Snowman, E, E-mail: ek2002@wildcats.unh.edu [Department of Natural Resources and the Environment, University of New Hampshire, Durham, NH03824 (United States); Shaw, JR, E-mail: joeshaw@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Chen, CY, E-mail: Celia.Y.Chen@dartmouth.edu [Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States)

2017-01-01

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.

Whole body irradiation in paediatrics: in vivo dose heterogeneity and relationship with survival and the complications rate

International Nuclear Information System (INIS)

Paoli, J.B.; Pignon, T.; Porcheron, D.; Juin, P.; Coze, C.; Bernard, J.L.

2000-01-01

No relationship has been found between the in vivo measured dose and the survival, neither relationship between the measured dose and the toxicity. The only organ for which an inter patients heterogeneity has been found was the lung. The reduction of the lung radiation dose allows to avoid any interstitial pneumopathy, but is significantly associated to a shortening of the survival. (N.C.)

Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship

International Nuclear Information System (INIS)

Erselcan, Taner; Ozdemir, Semra; Turgut, Bulent; Dogan, Derya; Sungu, Selma; Ozdemir, Ozturk

2004-01-01

Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of 131 I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean±SD) were 3.19±0.93, 10.83±1.72 and 5.75±2.06, respectively, in the whole group, and these values differed significantly from each other (P 131 I dose in the whole group, but a negative correlation was found between the 131 I dose and the RR at the 6th month (r=-0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x-28.4x 2 +38.1 (R 2 =0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of 131 I and DR and RR were obtained with a linear-quadratic model (Y=αD+βD 2 ) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient β to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following 131 I treatment. Further studies are therefore needed to clarify the effect of the negative β value on the biological dosimetry approach in continuous internal low LET radiation, as in the case

YOUNG ADULT DATING RELATIONSHIPS AND THE MANAGEMENT OF SEXUAL RISK.

Science.gov (United States)

Manning, Wendy D; Giordano, Peggy C; Longmore, Monica A; Flanigan, Christine M

2012-04-01

Young adult involvement in sexual behavior typically occurs within a relationship context, but we know little about the ways in which specific features of romantic relationships influence sexual decision-making. Prior work on sexual risk taking focuses attention on health issues rather than relationship dynamics. We draw on data from the Toledo Adolescent Relationships Study (TARS) (n = 475) to examine the association between qualities and dynamics of current/most recent romantic relationships such as communication and emotional processes, conflict, demographic asymmetries, and duration and the management of sexual risk. We conceptualize 'risk management' as encompassing multiple domains, including (1) questioning the partner about previous sexual behaviors/risks, (2) using condoms consistently, and (3) maintaining sexual exclusivity within the relationship. We identify distinct patterns of risk management among dating young adults and find that specific qualities and dynamics of these relationships are linked to variations in risk management. Results from this paper suggest the need to consider relational dynamics in efforts to target and influence young adult sexual risk-taking and reduce STIs, including HIV.

YOUNG ADULT DATING RELATIONSHIPS AND THE MANAGEMENT OF SEXUAL RISK

Science.gov (United States)

Manning, Wendy D.; Giordano, Peggy C.; Longmore, Monica A.; Flanigan, Christine M.

2012-01-01

Young adult involvement in sexual behavior typically occurs within a relationship context, but we know little about the ways in which specific features of romantic relationships influence sexual decision-making. Prior work on sexual risk taking focuses attention on health issues rather than relationship dynamics. We draw on data from the Toledo Adolescent Relationships Study (TARS) (n = 475) to examine the association between qualities and dynamics of current/most recent romantic relationships such as communication and emotional processes, conflict, demographic asymmetries, and duration and the management of sexual risk. We conceptualize ‘risk management’ as encompassing multiple domains, including (1) questioning the partner about previous sexual behaviors/risks, (2) using condoms consistently, and (3) maintaining sexual exclusivity within the relationship. We identify distinct patterns of risk management among dating young adults and find that specific qualities and dynamics of these relationships are linked to variations in risk management. Results from this paper suggest the need to consider relational dynamics in efforts to target and influence young adult sexual risk-taking and reduce STIs, including HIV. PMID:23805015

Foetal Radiation Dose and Risk from Diagnostic Radiology Procedures: A Multinational Study

International Nuclear Information System (INIS)

Osei, Ernest K.; Darko, Johnson

2012-01-01

In diagnostic radiology examinations there is a benefit that the patient derives from the resulting diagnosis. Given that so many examinations are performed each year, it is inevitable that there will be occasions when an examination(s) may be inadvertently performed on pregnant patients or occasionally it may become clinically necessary to perform an examination(s) on a pregnant patient. In all these circumstances it is necessary to request an estimation of the foetal dose and risk. We initiated a study to investigate fetal doses from different countries. Exposure techniques on 367 foetuses from 414 examinations were collected and investigated. The FetDoseV4 program was used for all dose and risk estimations. The radiation doses received by the 367 foetuses ranges: <0.001–21.9 mGy depending on examination and technique. The associated probability of induced hereditary effect ranges: <1 in 200000000 (5 × 10 −9 ) to 1 in 10000 (1 × 10 −4 ) and the risk of childhood cancer ranges <1 in 12500000 (8 × 10 −8 ) to 1 in 500 (2 × 10 −3 ). The data indicates that foetal doses from properly conducted diagnostic radiology examinations will not result in any deterministic effect and a negligible risk of causing radiation induced hereditary effect in the descendants of the unborn child

Risks to health from radiation at low dose rates

International Nuclear Information System (INIS)

Gentner, N.E.; Osborne, R.V.

1997-01-01

Our focus is on whether, using a balance-of-evidence approach, it is possible to say that at a low enough dose, or at a sufficiently low dose rate, radiation risk reduces to zero in a population. We conclude that insufficient evidence exists at present to support such a conclusion. In part this reflects statistical limitations at low doses, and in part (although mechanisms unquestionably exist to protect us against much of the damage induced by ionizing radiation) the biological heterogeneity of human populations, which means these mechanisms do not act in all members of the population at all times. If it is going to be possible to demonstrate that low doses are less dangerous than we presently assume, the evidence, paradoxically, will likely come from studies of higher dose and dose rate scenarios than are encountered occupationally. (author)

Hiroshima and Nagasaki: New doses, risks, and their implications

International Nuclear Information System (INIS)

Schull, W.J.; Shimizu, Y.; Kato, H.

1990-01-01

This presentation summarizes the recent re-evaluations of the dose and risk of cancer among survivors of the atomic bombing of Hiroshima and Nagasaki. It addresses briefly their limitations, and describes some of their implications for the lifetime projection of the risk of a fatal cancer following exposure to ionizing radiation

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Science.gov (United States)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose

Excipient Usage Technical Risk Assessment for Generic Solid Dose Products

Directory of Open Access Journals (Sweden)

Ajay Babu Pazhayattil

2017-09-01

Full Text Available This paper proposes an assessment methodology for solid dose generic small molecule drug products. It addresses the ‘usage of the excipient’ portion of the trinomial by utilizing the systematic approach of Risk Identification, Risk Analysis and Risk Evaluation as per ICH Q9 Quality Risk Management outlined for developing risk control strategies. The assessment and maintenance of excipient risk profile is essential to minimize any potential risk associated to excipients impacting patients.

Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model

DEFF Research Database (Denmark)

Larsen, Malte Selch; Keizer, Ron; Munro, Gordon

2016-01-01

PURPOSE: Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA......-induced inflammatory hyperalgesia. METHODS: A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration...

Probabilistic relationships in acceptable risk studies

International Nuclear Information System (INIS)

Benjamin, J.R.

1977-01-01

Acceptable risk studies involve uncertainties in future events; consequences and associated values, the acceptability levels, and the future decision environment. Probabilistic procedures afford the basic analytical tool to study the influence of each of these parameters on the acceptable risk decision, including their interrelationships, and combinations. A series of examples are presented in the paper in increasing complexity to illustrate the principles involved and to quantify the relationships to the acceptable risk decision. The basic objective of such studies is to broaden the scientific basis of acceptable risk decision making. It is shown that rationality and consistency in decision making is facilitated by such studies and that rather simple relationships exist in many situations of interest. The variation in criteria associated with an increase in the state of knowledge or change in the level of acceptability is also discussed. (Auth.)

Probabilistic relationships in acceptable risk studies

International Nuclear Information System (INIS)

Benjamin, J.R.

1977-01-01

Acceptable risk studies involve uncertainties in future events: consequences and associated values, the acceptability levels, and the future decision environment. Probabilistic procedures afford the basic analytical tool to study the influence of each of these parameters on the acceptable risk decision, including their interrelationships, and combinations. A series of examples are presented in the paper in increasing complexity to illustrate the principles involved and to quantify the relationships to the acceptable risk decision. The basic objective of such studies is to broaden the scientific basis of acceptable risk decision making. It is shown that rationality and consistency in decision making is facilitated by such studies and that rather simple relationships exist in many situations of interest. The variation in criteria associated with an increase in the state of knowledge or change in the level of acceptability is also discussed

The study on the dose-effect relationship of radiation from α particles of plutonium on certain lung cells (in vivo and in vitro)

International Nuclear Information System (INIS)

Wu Dechang; Ye Changqing; Gong Yifen; Yan Xiaoshan; Xie Guoliang; Liu Guolian; Chen Winchung; Hu Lianping; Shen Zhiyuan

1993-01-01

It is well known that plutonium is one of the most toxic radionuclides and its carcinogenic risk has been seriously concerned. In this study, the dose effect relationship of radiation from α particles of plutonium on certain lung cells (in vivo and in vitro) were investigated. The topics of study are as following: In vivo: deposition and clearance of Pu in respiratory tract, dose-effect relationship of lung cancer induced, histopathological type of lung cancer, primary hemangiosarcoma occurred in thoracic lumph node, radiation effects on Alveolar Macrophage (AM), radiation effect on Natural Killer Cell (NK) and radiation effect on Alveolar Type II (AT-II). In vitro: radiation effect on the immunological functions of AM, radiation effect on the membrane of AM, possible relationship between cytotoxicity and membranes of AM, effects of radiation (X, α) on the transformation of Wistar rat lung fibroblast cell line (WAL-F1) and protective effect of Se 4+ against transformation

Dose limits cause unacceptable risk

International Nuclear Information System (INIS)

Collier, Sylvia.

1985-01-01

This paper on radiation dose limits for workers and the public discusses the following: Medical Research Council report; safety standards; risk assessment; deaths from cancers; biological radiation effects; UK legislation; low-level radiation; public concern; UKAEA staff survey; Ionising Radiations Regulations; United Nations Scientific Committee on Effects of Atomic Radiation; US studies on work force in nuclear establishments; problems of extrapolation; Japanese data from Hiroshima and Nagasaki; International Commission on Radiological Protection recommendations; studies on uranium miners; UK Health and Safety Executive; UK National Radiological Protection Board. (U.K.)

Correlation between effective dose and radiological risk: general concepts

Energy Technology Data Exchange (ETDEWEB)

Costa, Paulo Roberto; Yoshimura, Elisabeth Mateus; Nersissian, Denise Yanikian; Melo, Camila Souza, E-mail: pcosta@if.usp.br [Universidade de Sao Paulo (IF/USP), Sao Paulo, SP (Brazil). Instituto de Fisica

2016-05-15

The present review aims to offer an educational approach related to the limitations in the use of the effective dose magnitude as a tool for the quantification of doses resulting from diagnostic applications of ionizing radiation. We present a critical analysis of the quantities accepted and currently used for dosimetric evaluation in diagnostic imaging procedures, based on studies published in the literature. It is highlighted the use of these quantities to evaluate the risk attributed to the procedure and to calculate the effective dose, as well as to determine its correct use and interpretation. (author)

Couple Relationship Functioning as a Source or Mitigator of HIV Risk: Associations Between Relationship Quality and Sexual Risk Behavior in Peri-urban Uganda.

Science.gov (United States)

Ruark, Allison; Kajubi, Phoebe; Ruteikara, Sam; Green, Edward C; Hearst, Norman

2018-04-01

Despite evidence that a greater focus on couples could strengthen HIV prevention efforts, little health-related research has explored relationship functioning and relationship quality among couples in Africa. Using data from 162 couples (324 individuals) resident in a peri-urban Ugandan community, we assessed actor and partner effects of sexual risk behaviors on relationship quality, using psychometric measures of dyadic adjustment, sexual satisfaction, commitment, intimacy, and communication. For women and men, poor relationship quality was associated with having concurrent sexual partners and suspecting that one's partner had concurrent sexual partners (actor effects). Women's poor relationship quality was also associated with men's sexual risk behaviors (partner effects), although the inverse partner effect was not observed. These findings suggest that relationship quality is linked to HIV risk, particularly through the pathway of concurrent sexual partnerships, and that positive relationship attributes such as sexual satisfaction, intimacy, and constructive communication can help couples to avoid risk.

Investigation of mean glandular dose versus compressed breast thickness relationship for mammography

International Nuclear Information System (INIS)

Bor, D.; Tukel, S.; Olgar, T.; Toklu, T.; Aydin, E.; Akyol, O.

2008-01-01

The relationship between the mean glandular dose (MGD) and the compressed breast thickness (CBT) is commonly used for the presentation of mammographic dose survey results and could also be useful for the assessment of individual breast doses retrospectively in case of lack of necessary dosimetric instrumentation. The high data scattering from the best fit reduces the reliability of this technique. The aim of this study was to investigate the accuracy of this relationship using the data collected from a patient survey and phantom experiment. Patients were divided into three different groups according to their breast glandularities, which were predicted from the inspection of previous mammograms. X-ray beam qualities that will be used in patient examinations were determined according to breast thickness and predicted glandularities. The MGD versus CBT relationship for all the examined patients resulted in a poor correlation (R 2 = 0.28). This relationship was separately obtained for each glandularity group and also for sub-groups of specific beam qualities. The best correlation (R 2 = 0.73) was obtained for the fatty breast group and Mo/Mo combination. A low correlation (R 2 = 0.34) was observed in the mid-glandularity group due to inclusion of a wide range of glandularities in this group. In the case of the dense breast group, although the glandularity range was narrow, there were e still high data scattering (R 2 = 0.25). This was probably due to the use of Mo/Rh and Mo/Mo combinations. This is validated by obtaining the MGD-CBT relationship specific to Mo/Mo combination (R 2 = 0.61). (authors)

Medulloblastoma: time-dose relationship based on a 30-year review

International Nuclear Information System (INIS)

Charco, John O. del; Bolek, Timothy W.; McCollough, W. Mark; Maria, Bernard L.; Kedar, Amos; Braylan, Raul C.; Mickle, J. Parker; Buatti, John M.; Mendenhall, Nancy P.; Marcus, Robert B.

1998-01-01

Purpose: Time-dose relationships have proven important in many cancer sites. This study evaluates the time factors involved in the successful postoperative radiotherapy of medulloblastoma, based on a 30-year experience in a single institution. Methods and Materials: Fifty-three patients with medulloblastoma received postoperative craniospinal radiotherapy with curative intent between 1963 and 1993. Seven patients (13%) underwent biopsy alone, 28 patients (53%) had subtotal excision, and 18 patients (34%) had gross total excision. Eleven patients received adjuvant chemotherapy. The mean posterior fossa dose was 53.1 Gy; most patients received 54.0 Gy (range, 34.3 to 69.6 Gy). For 41 patients receiving once-a-day therapy, the mean dose was 50.6 Gy (range, 34.3 to 56.0 Gy). For 12 patients receiving twice-a-day therapy, the mean dose was 61.8 Gy (range, 52.6 to 69.6 Gy). Minimum follow-up was 2 years, and median follow-up was 10.7 years. Survival, freedom from relapse, and disease control in the posterior fossa were calculated using the Kaplan-Meier method, and multivariate analysis was performed for prognostic factors. Variables related to radiotherapy were examined, including dose to the craniospinal axis, dose to the posterior fossa, fractionation (once-a-day vs. twice-a-day), use of adjuvant chemotherapy, risk group [high (≥T3b or ≥M1) or low (≤T3a and M0-MX)], interval between surgery and radiotherapy (excluding patients receiving chemotherapy before radiotherapy), and duration of radiotherapy. Results: At 5 and 10 years, overall survival rates were 68 and 64%, respectively, and freedom-from-relapse rates were 61 and 52%, respectively. Rates of disease control in the posterior fossa at 5 and 10 years were 79 and 68%, respectively. At 5 years, absolute survival rates after biopsy alone, subtotal excision, and gross total excision were 43, 67, and 78%, respectively (p = 0.04), and posterior fossa control rates were 27, 89, and 83%, respectively (p = 0

Modelling long term rockslide displacements with non-linear time-dependent relationships

Science.gov (United States)

De Caro, Mattia; Volpi, Giorgio; Castellanza, Riccardo; Crosta, Giovanni; Agliardi, Federico

2015-04-01

Rockslides undergoing rapid changes in behaviour pose major risks in alpine areas, and require careful characterization and monitoring both for civil protection and mitigation activities. In particular, these instabilities can undergo very slow movement with occasional and intermittent acceleration/deceleration stages of motion potentially leading to collapse. Therefore, the analysis of such instabilities remains a challenging issue. Rockslide displacements are strongly conditioned by hydrologic factors as suggested by correlations with groundwater fluctuations, snowmelt, with a frequently observed delay between perturbation and system reaction. The aim of this work is the simulation of the complex time-dependent behaviour of two case studies for which also a 2D transient hydrogeological simulation has been performed: Vajont rockslide (1960 to 1963) and the recent Mt. de La Saxe rockslide (2009 to 2012). Non-linear time-dependent constitutive relationships have been used to describe long-term creep deformation. Analyses have been performed using a "rheological-mechanical" approach that fits idealized models (e.g. viscoelastic, viscoplastic, elasto-viscoplastic, Burgers, nonlinear visco-plastic) to the experimental behaviour of specific materials by means of numerical constants. Bidimensional simulations were carried out using the finite difference code FLAC. Displacements time-series, available for the two landslides, show two superimposed deformation mechanisms: a creep process, leading to movements under "steady state" conditions (e.g. constant groundwater level), and a "dynamic" process, leading to an increase in displacement rate due to changes of external loads (e.g. groundwater level). For both cases sliding mass is considered as an elasto-plastic body subject to its self-weight, inertial and seepage forces varying with time according to water table fluctuation (due to snowmelt or changing in reservoir level) and derived from the previous hydrogeological

Effective doses and standardised risk factors from paediatric diagnostic medical radiation exposures: Information for radiation risk communication

International Nuclear Information System (INIS)

Bibbo, Giovanni

2018-01-01

In the paediatric medical radiation setting, there is no consistency on the radiation risk information conveyed to the consumer (patient/carer). Each communicator may convey different information about the level of risk for the same radiation procedure, leaving the consumer confused and frustrated. There is a need to standardise risks resulting from medical radiation exposures. In this study, paediatric radiographic, fluoroscopic, CT and nuclear medicine examination data have been analysed to provide (i) effective doses and radiation induced cancer risk factors from common radiological and nuclear medicine diagnostic procedures in standardised formats, (II) awareness of the difficulties that may be encountered in communicating risks to the layperson, and (iii) an overview of the deleterious effects of ionising radiation so that the risk communicator can convey with confidence the risks resulting from medical radiation exposures. Paediatric patient dose data from general radiographic, computed tomography, fluoroscopic and nuclear medicine databases have been analysed in age groups 0 to <5 years, 5 to <10 years, 10 to <15 years and 15 to <18 years to determine standardised risk factors. Mean, minimum and maximum effective doses and the corresponding mean lifetime risks for general radiographic, fluoroscopic, CT and nuclear medicine examinations for different age groups have been calculated. For all examinations, the mean lifetime cancer induction risk is provided in three formats: statistical, fraction and category. Standardised risk factors for different radiological and nuclear medicine examinations and an overview of the deleterious effects of ionising radiation and the difficulties encountered in communicating the risks should facilitate risk communication to the patient/carer.

Effects of low doses

International Nuclear Information System (INIS)

Le Guen, B.

2001-01-01

Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

Insignificant levels of dose

International Nuclear Information System (INIS)

Webb, G.A.M.; McLean, A.S.

1977-01-01

The procedures recommended by the International Commission on Radiological Protection (ICRP) for making decisions concerning controllable sources of radiation exposure of the public include 'justification' and 'optimisation'. The tool recommended by the ICRP for reaching these decisions is collective dose or dose commitment supplemented by consideration of doses to individuals. In both these considerations the practical problem arises of whether very small doses to large numbers of people should contribute to the final decision-making process. It may be that at levels of dose which are small increments on natural background, the relationship between dose and effect is linear even though the slope may be close to zero. If so, collective dose is a meaningful concept and the calculation of total detriment for the purpose of justification could legitimately include all doses. In the calculation of collective doses for the purpose of optimisation, which involves decisions on how much money or resource should be allocated to dose reduction, it is necessary to appraise radiation detriment realistically. At low levels of dose to the individual such as those small by comparison with variations in natural background within the UK, the risk to the individual is such that his well-being will not be significantly changed by the presence or absence of the radiation dose. These small doses, which are well below the point at which an individual attaches significance, should not carry a societal significance. Societal acceptance of risk is analysed with a view to assessing a level of possible risk, and hence dose, below which resources should not in general be diverted to secure further reduction. A formulation for collective dose commitment is proposed incorporating a cut-off to exclude insignificant doses. The implications of this formulation in practical situations are discussed

Current features on risk perception and risk communication of radiation

International Nuclear Information System (INIS)

Kusama, Tomoko

1997-01-01

Health effects and risks of radiation and radionuclides are being misunderstood by many members of general public. Many peoples have fear and anxieties for radiation. So far, the health effects from radiation at low dose and low dose rate have not been cleared on biological aspects. Then, we have quantitatively estimated health risks of low-dose radiation on the basis of linear dose response relationship without threshold from the viewpoints of radiation protection by using both epidemiological data, such as atomic bomb survivors, and some models and assumptions. It is important for researchers and relevant persons in radiation protection to understand the process of risk estimation of radiation and to communicate an exact knowledge of radiation risks of the public members. (author)

A nonlinear isobologram model with Box-Cox transformation to both sides for chemical mixtures.

Science.gov (United States)

Chen, D G; Pounds, J G

1998-12-01

The linear logistical isobologram is a commonly used and powerful graphical and statistical tool for analyzing the combined effects of simple chemical mixtures. In this paper a nonlinear isobologram model is proposed to analyze the joint action of chemical mixtures for quantitative dose-response relationships. This nonlinear isobologram model incorporates two additional new parameters, Ymin and Ymax, to facilitate analysis of response data that are not constrained between 0 and 1, where parameters Ymin and Ymax represent the minimal and the maximal observed toxic response. This nonlinear isobologram model for binary mixtures can be expressed as [formula: see text] In addition, a Box-Cox transformation to both sides is introduced to improve the goodness of fit and to provide a more robust model for achieving homogeneity and normality of the residuals. Finally, a confidence band is proposed for selected isobols, e.g., the median effective dose, to facilitate graphical and statistical analysis of the isobologram. The versatility of this approach is demonstrated using published data describing the toxicity of the binary mixtures of citrinin and ochratoxin as well as a new experimental data from our laboratory for mixtures of mercury and cadmium.

Estimation of effective dose and lifetime attributable risk from multiple head CT scans in ventriculoperitoneal shunted children

International Nuclear Information System (INIS)

Aw-Zoretic, J.; Seth, D.; Katzman, G.; Sammet, S.

2014-01-01

Purpose: The purpose of this review is to determine the averaged effective dose and lifetime attributable risk factor from multiple head computed tomography (CT) dose data on children with ventriculoperitoneal shunts (VPS). Method and materials: A total of 422 paediatric head CT exams were found between October 2008 and January 2011 and retrospectively reviewed. The CT dose data was weighted with the latest IRCP 103 conversion factor to obtain the effective dose per study and the averaged effective dose was calculated. Estimates of the lifetime attributable risk were also calculated from the averaged effective dose using a conversion factor from the latest BEIR VII report. Results: Our study found the highest effective doses in neonates and the lowest effective doses were observed in the 10–18 years age group. We estimated a 0.007% potential increase risk in neonates and 0.001% potential increased risk in teenagers over the base risk. Conclusion: Multiple head CTs in children equates to a slight potential increase risk in lifetime attributable risk over the baseline risk for cancer, slightly higher in neonates relative to teenagers. The potential risks versus clinical benefit must be assessed

Sleep duration and risk of all-cause mortality: A flexible, non-linear, meta-regression of 40 prospective cohort studies.

Science.gov (United States)

Liu, Tong-Zu; Xu, Chang; Rota, Matteo; Cai, Hui; Zhang, Chao; Shi, Ming-Jun; Yuan, Rui-Xia; Weng, Hong; Meng, Xiang-Yu; Kwong, Joey S W; Sun, Xin

2017-04-01

Approximately 27-37% of the general population experience prolonged sleep duration and 12-16% report shortened sleep duration. However, prolonged or shortened sleep duration may be associated with serious health problems. A comprehensive, flexible, non-linear meta-regression with restricted cubic spline (RCS) was used to investigate the dose-response relationship between sleep duration and all-cause mortality in adults. Medline (Ovid), Embase, EBSCOhost-PsycINFO, and EBSCOhost-CINAHL Plus databases, reference lists of relevant review articles, and included studies were searched up to Nov. 29, 2015. Prospective cohort studies investigating the association between sleep duration and all-cause mortality in adults with at least three categories of sleep duration were eligible for inclusion. We eventually included in our study 40 cohort studies enrolling 2,200,425 participants with 271,507 deaths. A J-shaped association between sleep duration and all-cause mortality was present: compared with 7 h of sleep (reference for 24-h sleep duration), both shortened and prolonged sleep durations were associated with increased risk of all-cause mortality (4 h: relative risk [RR] = 1.05; 95% confidence interval [CI] = 1.02-1.07; 5 h: RR = 1.06; 95% CI = 1.03-1.09; 6 h: RR = 1.04; 95% CI = 1.03-1.06; 8 h: RR = 1.03; 95% CI = 1.02-1.05; 9 h: RR = 1.13; 95% CI = 1.10-1.16; 10 h: RR = 1.25; 95% CI = 1.22-1.28; 11 h: RR = 1.38; 95% CI = 1.33-1.44; n = 29; P < 0.01 for non-linear test). With regard to the night-sleep duration, prolonged night-sleep duration was associated with increased all-cause mortality (8 h: RR = 1.01; 95% CI = 0.99-1.02; 9 h: RR = 1.08; 95% CI = 1.05-1.11; 10 h: RR = 1.24; 95% CI = 1.21-1.28; n = 13; P < 0.01 for non-linear test). Subgroup analysis showed females with short sleep duration a day (<7 h) were at high risk of all-cause mortality (4 h: RR = 1.07; 95% CI = 1.02-1.13; 5 h: RR = 1.08; 95

Risk and responsibility: a complex and evolving relationship.

Science.gov (United States)

Kermisch, Céline

2012-03-01

This paper analyses the nature of the relationship between risk and responsibility. Since neither the concept of risk nor the concept of responsibility has an unequivocal definition, it is obvious that there is no single interpretation of their relationship. After introducing the different meanings of responsibility used in this paper, we analyse four conceptions of risk. This allows us to make their link with responsibility explicit and to determine if a shift in the connection between risk and responsibility can be outlined. (1) In the engineer's paradigm, the quantitative conception of risk does not include any concept of responsibility. Their relationship is indirect, the locus of responsibility being risk management. (2) In Mary Douglas' cultural theory, risks are constructed through the responsibilities they engage. (3) Rayner and (4) Wolff go further by integrating forms of responsibility in the definition of risk itself. Analysis of these four frameworks shows that the concepts of risk and responsibility are increasingly intertwined. This tendency is reinforced by increasing public awareness and a call for the integration of a moral dimension in risk management. Therefore, we suggest that a form of virtue-responsibility should also be integrated in the concept of risk. © Springer Science+Business Media B.V. 2010

Dose-Response Association Between Physical Activity and Incident Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies.

Science.gov (United States)

Liu, Xuejiao; Zhang, Dongdong; Liu, Yu; Sun, Xizhuo; Han, Chengyi; Wang, Bingyuan; Ren, Yongcheng; Zhou, Junmei; Zhao, Yang; Shi, Yuanyuan; Hu, Dongsheng; Zhang, Ming

2017-05-01

Despite the inverse association between physical activity (PA) and incident hypertension, a comprehensive assessment of the quantitative dose-response association between PA and hypertension has not been reported. We performed a meta-analysis, including dose-response analysis, to quantitatively evaluate this association. We searched PubMed and Embase databases for articles published up to November 1, 2016. Random effects generalized least squares regression models were used to assess the quantitative association between PA and hypertension risk across studies. Restricted cubic splines were used to model the dose-response association. We identified 22 articles (29 studies) investigating the risk of hypertension with leisure-time PA or total PA, including 330 222 individuals and 67 698 incident cases of hypertension. The risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.96) with each 10 metabolic equivalent of task h/wk increment of leisure-time PA. We found no evidence of a nonlinear dose-response association of PA and hypertension ( P nonlinearity =0.094 for leisure-time PA and 0.771 for total PA). With the linear cubic spline model, when compared with inactive individuals, for those who met the guidelines recommended minimum level of moderate PA (10 metabolic equivalent of task h/wk), the risk of hypertension was reduced by 6% (relative risk, 0.94; 95% confidence interval, 0.92-0.97). This meta-analysis suggests that additional benefits for hypertension prevention occur as the amount of PA increases. © 2017 American Heart Association, Inc.

Estimating doses and risks associated with decontamination and decommissioning activities using the CRRIS

International Nuclear Information System (INIS)

Miller, C.W.; Sjoreen, A.L.; Cotter, S.J.

1986-01-01

The Computerized Radiological Risk Investigation System (CRRIS) is applicable to determining doses and risks from a variety of decontamination and decommissioning activities. For example, concentrations in air from resuspended radionuclides initially deposited on the ground surface and the concentrations of deposited radionuclides in various soil layers can be obtained. The CRRIS will estimate exposure to radon and its progeny in terms of working-level months, and will compute the resulting health risks. The CRRIS consists of seven integrated computer codes that stand alone or are run as a system to calculate environmental transport, doses, and risks. PRIMUS output provides other CRRIS codes the capability to handle radionuclide decay chains. ANEMOS and RETADD-II calculate atmospheric dispersion and deposition for local and regional distances, respectively. Multiple ANEMOS runs for sources within a small area are combined on a master grid by SUMIT. MLSOIL is used to estimate effective ground surface concentrations for dose computations. TERRA calculates food chain transport, and ANDROS calculates individual or population exposures, doses, and risks. Applications of the CRRIS to decontamination problems are discussed. 16 refs., 1 fig

Relationship between human tooth enamel free radical concentration and radiation dose

International Nuclear Information System (INIS)

Zhou Yongzeng; Wang Jiadong; Jia Xiaomei; Wu Ke; Cong Jianbo; Sun Cunpu

1999-01-01

Free radical concentrations of 25 adult tooth enamel samples were measured by electron spin resonance (ESR) technique in this paper, and the relationship between free radical concentration of tooth enamel and radiation dose was also investigated. In the 25 adult enamel samples they are 16 male samples and 9 female samples, Ages of tooth donors range from 18-41 years. Difference in background ESR signal intensity between male and female samples was no observed; free radical concentration (or increment of radiation-induced free radical concentration) in tooth enamel increases linearly with increasing of radiation dose. In the case of radiation accident, the study results of this paper could be applied to dose estimation when conditions of ESR measurement of exposed individual tooth enamel are similar to measurement conditions of dose-effect calibration curve in this paper

Nonlinear Kalman Filtering in Affine Term Structure Models

DEFF Research Database (Denmark)

Christoffersen, Peter; Dorion, Christian; Jacobs, Kris

When the relationship between security prices and state variables in dynamic term structure models is nonlinear, existing studies usually linearize this relationship because nonlinear fi…ltering is computationally demanding. We conduct an extensive investigation of this linearization and analyze...... the potential of the unscented Kalman …filter to properly capture nonlinearities. To illustrate the advantages of the unscented Kalman …filter, we analyze the cross section of swap rates, which are relatively simple non-linear instruments, and cap prices, which are highly nonlinear in the states. An extensive...

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

Science.gov (United States)

Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

Patient and staff doses and relationships between them in fluoroscopically guided procedures

International Nuclear Information System (INIS)

Avramova-Cholakova, S.; Christova-Popova, Y.; Sagorska, A.

2015-01-01

Full text: Medical exposure has the main contribution to man-made sources of exposures to the population in developed countries. Fluoroscopically guided procedures in interventional cardiology, gastroenterology, urology, orthopaedics and others may be related to high doses to both patients and staff. The main risk for both groups is the radiation carcinogenesis and it is increasing with dose. However deterministic effects are also possible: severe patient skin injuries occur sometimes. There are such cases in Bulgarian radiological practice. For the medical staff, involved in the procedures, radiation induced cataract is observed occasionally. Learning objective: In many cases there is direct correlation between patient and staff doses. Several simple rules must be observed in order to decrease exposure. Rules related to patient: Patient dose (dose-area product (DAP), fluoroscopy time, number of series,number of images) should be recorded for every patient; The patient should be positioned as far away as possible from the x-ray tube and as closer as possible to the image intensifier/digital image receptor; Fluoroscopy time should be minimized; Pulsed fluoroscopy with the lowest dose rate and the lowest frame rate providing acceptable image quality should be used; Different skin areas should be exposed in different projections; Oblique projections increase the dose - they should be avoided; Magnification also increases the dose several times and should be avoided; The acquisition mode should be avoided; it delivers dozens of times higher doses. Minimal number of frames and cine runs should be used. Use of “last image hold” is encouraged; The x-ray beam should be collimated to the area of interest. Rules related to staff: The staff receives scattered radiation from patient’s body. Every measure to decrease patient’s dose decreases staff dose as well; Every available protective device should be used (lead apron, thyroid collar, lead glasses, screens). They

Risk of cancer in the vicinity of municipal solid waste incinerators: importance of using a flexible modelling strategy

Directory of Open Access Journals (Sweden)

Goria Sarah

2009-05-01