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Sample records for biologically effective dose-response

  1. Biological effects in lymphocytes irradiated with 99mTc: determination of the curve dose-response

    International Nuclear Information System (INIS)

    Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with 99m Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with 99m Tc were used, allowing the irradiation of blood with different administered activities of 99m Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with 99m Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with 99m Tc was best fitted by the curve Y=(8,99 ±2,06) x 1--4 + (1,24 ±0,62) x 10-2 D + (5,67 ± 0,64) x 10-2 D2. (author)

  2. Molecular circuits, biological switches, and nonlinear dose-response relationships.

    OpenAIRE

    Andersen, Melvin E.; Yang, Raymond S.H.; French, C. Tenley; Chubb, Laura S; Dennison, James E

    2002-01-01

    Signaling motifs (nuclear transcriptional receptors, kinase/phosphatase cascades, G-coupled protein receptors, etc.) have composite dose-response behaviors in relation to concentrations of protein receptors and endogenous signaling molecules. "Molecular circuits" include the biological components and their interactions that comprise the workings of these signaling motifs. Many of these molecular circuits have nonlinear dose-response behaviors for endogenous ligands and for exogenous toxicants...

  3. Low-dose neutron dose response of zebrafish embryos obtained from the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility

    International Nuclear Information System (INIS)

    The dose response of embryos of the zebrafish, Danio rerio, irradiated at 5 h post fertilization (hpf) by 2-MeV neutrons with ≤100 mGy was determined. The neutron irradiations were made at the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility in the National Institute of Radiological Sciences (NIRS), Chiba, Japan. A total of 10 neutron doses ranging from 0.6 to 100 mGy were employed (with a gamma-ray contribution of 14% to the total dose), and the biological effects were studied through quantification of apoptosis at 25 hpf. The responses for neutron doses of 10, 20, 25, and 50 mGy approximately fitted on a straight line, while those for neutron doses of 0.6, 1 and 2.5 mGy exhibited neutron hormetic effects. As such, hormetic responses were generically developed by different kinds of ionizing radiations with different linear energy transfer (LET) values. The responses for neutron doses of 70 and 100 mGy were significantly below the lower 95% confidence band of the best-fit line, which strongly suggested the presence of gamma-ray hormesis. - Highlights: • Neutron dose response was determined for embryos of the zebrafish, Danio rerio. • Neutron doses of 0.6, 1 and 2.5 mGy led to neutron hormetic effects. • Neutron doses of 70 and 100 mGy accompanied by gamma rays led to gamma-ray hormesis

  4. Biologically effective uniform dose (D) for specification, report and comparison of dose response relations and treatment plans

    International Nuclear Information System (INIS)

    Developments in radiation therapy planning have improved the information about the three-dimensional dose distribution in the patient. Isodose graphs, dose volume histograms and most recently radiobiological models can be used to evaluate the dose distribution delivered to the irradiated organs and volumes of interest. The concept of a biologically effective uniform dose (D) assumes that any two dose distributions are equivalent if they cause the same probability for tumour control or normal tissue complication. In the present paper the D concept both for tumours and normal tissues is presented, making use of the fact that probabilities averaged over both dose distribution and organ radiosensitivity are more relevant to the clinical outcome than the expected number of surviving clonogens or functional subunits. D can be calculated in complex target volumes or organs at risk either from the 3D dose matrix or from the corresponding dose volume histograms of the dose plan. The value of the D concept is demonstrated by applying it to two treatment plans of a cervix cancer. Comparison is made of the D concept with the effective dose (Deff) and equivalent uniform dose (EUD) that have been suggested in the past. The value of the concept for complex targets and fractionation schedules is also pointed out. (author)

  5. Non-Linear Dose Response Relationships in Biology, Toxicology, and Medicine (June 8-10, 2004). Final Report

    International Nuclear Information System (INIS)

    The conference attracts approximately 500 scientists researching in the area of non-linear low dose effects. These scientists represent a wide range of biological/medical fields and technical disciplines. Observations that biphasic dose responses are frequently reported in each of these areas but that the recognition of similar dose response relationships across disciplines is very rarely appreciated and exploited. By bringing scientist of such diverse backgrounds together who are working on the common area of non-linear dose response relationships this will enhance our understanding of the occurrence, origin, mechanism, significance and practical applications of such dose response relationships

  6. Biological effects in lymphocytes irradiated with {sup 99m}Tc: determination of the curve dose-response; Efeitos biologicos em linfocitos irradiados com {sup 99m}Tc: determinacao da curva dose-resposta

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Romero Marcilio Barros Matias de

    2002-08-01

    Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with {sup 99m} Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with {sup 99m} Tc were used, allowing the irradiation of blood with different administered activities of {sup 99m} Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with {sup 99m} Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with {sup 99m} Tc was best fitted by the curve Y=(8,99 {+-}2,06) x 1-{sup -4} + (1,24 {+-}0,62) x 10{sup -2} D + (5,67 {+-} 0,64) x 10{sup -2} D{sup 2}. (author)

  7. Alcohol and cirrhosis: dose--response or threshold effect?

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Grønbaek, Morten; Tolstrup, Janne;

    2004-01-01

    BACKGROUND/AIMS: General population studies have shown a strong association between alcohol intake and death from alcoholic cirrhosis, but whether this is a dose-response or a threshold effect remains unknown, and the relation among alcohol misusers has not been studied. METHODS: A cohort of 6152...... alcohol misusing men and women aged 15-83 were interviewed about drinking pattern and social issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis mortality. Data was analyzed by means of Cox-regression models. RESULTS: In this large prospective cohort study of alcohol misusers...... there was a 27 fold increased mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from alcoholic cirrhosis in women compared to the Danish population. Number of drinks per day was not significantly associated with death from alcoholic cirrhosis, since there was no additional risk of death...

  8. The impact of different dose response parameters on biologically optimized IMRT in breast cancer

    Science.gov (United States)

    Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

    2008-05-01

    The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients

  9. The impact of different dose-response parameters on biologically optimized IMRT in breast cancer

    International Nuclear Information System (INIS)

    The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I-II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose, dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose-response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump

  10. Similarity criterion analysis of dose-response curves in biological assay and radioimmunoassay of hormones

    International Nuclear Information System (INIS)

    The difficulties involved in the control of biological and radioimmunological assay systems, and in the maintenance of standard, as well as, the usual heterogeneity of assayed samples require some evidence of similarity between the dose-response curves obtained with the standard and the sample. Nowadays the parallelism test is used to provide such evidence. However, some indications of non-normal errors distribution, such as the presence of out layers, render the parallelism test both conceptually implausible and statistically inefficient. In such a manner we suggest the non-parametric 'frequencial' test as a more sounding option. (author)

  11. The effect of measurement error on the dose-response curve.

    OpenAIRE

    Yoshimura, I

    1990-01-01

    In epidemiological studies for an environmental risk assessment, doses are often observed with errors. However, they have received little attention in data analysis. This paper studies the effect of measurement errors on the observed dose-response curve. Under the assumptions of the monotone likelihood ratio on errors and a monotone increasing dose-response curve, it is verified that the slope of the observed dose-response curve is likely to be gentler than the true one. The observed variance...

  12. Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves

    International Nuclear Information System (INIS)

    Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health

  13. Dose response curves for effects of low-level radiation

    International Nuclear Information System (INIS)

    The linear dose-response model used by international committees to assess the genetic and carcinogenic hazards of low-level radiation appears to be the most reasonable interpretation of the available scientific data that are relevant to this topic. There are, of course, reasons to believe that this model may overestimate radiation hazards in certain instances, a fact acknowledged in recent reports of these committees. The linear model is now also being utilized to estimate the potential carcinogenic hazards of other agents such as asbestos and polycyclic aromatic hydrocarbons. This model implies that there is no safe dose for any of these agents and that potential health hazards will increase in direct proportion to total accumulated dose. The practical implication is the recommendation that all exposures should be kept 'as low as reasonably achievable, economic and social factors being taken into account'. (auth)

  14. Radiation effects on livestock: physiological effects, dose response

    International Nuclear Information System (INIS)

    Farm livestock show no measurable effects from being exposed to ionizing radiation unless the level is greatly in excess of the natural background radiation. Possible sources of ionizing radiation which might affect livestock or contribute to radioactivity in the food chain to humans are reactor accidents, fuel reprocessing plant accidents and thermonuclear explosions. Most data on ionizing radiation effects on livestock are from whole body gamma doses near the LD 50/60 level. However, grazing livestock would be subjected to added beta exposure from ingested and skin retained radioactive particles. Results of attempts to simulate exposure of the Hereford cattle at Alamogardo, NM show that cattle are more sensitive to ingested fallout radiation than other species. Poultry LD 50/60 for gamma exposure is about twice the level for mammals, and swine appear to have the most efficient repair system being able to withstand the most chronic gamma exposure. Productivity of most livestock surviving an LD 50/60 exposure is temporarily reduced and longterm effects are small. Livestock are good screeners against undesirables in our diet and with the exception of radiosotopes of iodine in milk, very little fission product radioactivity would be expected to be transferred through the food chain in livestock products for humans. Feeding of stored feed or moving livestock to uncontaminated pastures would be the best protective action to follow. 29 references

  15. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework

    International Nuclear Information System (INIS)

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines

  16. Biological dosimetry in radiological protection: dose response curves elaboration for 60Co and 137Cs

    International Nuclear Information System (INIS)

    Ionizing radiation sources for pacific uses are being extensively utilized by modern society and the applications of these sources have raised the probability of the occurrence of accidents. The accidental exposition to radiation creates a necessity of the development of methods to evaluate dose quantity. This data could be obtained by the measurement of damage caused by radiation in the exposed person. The radiation dose can be estimated in exposed persons through physical methods (physical dosimetry) but the biological methods can't be dispensed, and among them, the cytogenetic one that makes use of chromosome aberrations (dicentric and centric ring) formed in peripheral blood lymphocytes (PBL) exposed to ionizing radiation. This method correlates the frequency of radioinduced aberrations with the estimated absorbed dose, as in vitro as in vivo, which is called cytogenetic dosimetry. By the introduction of improved new techniques in culture, in the interpretation of aberrations in the different analysers of slides and by the adoption of different statistical programs to analyse the data, significant differences are observed among laboratories in dose-response curves (calibration curves). The estimation of absorbed dose utilizing other laboratory calibration curves may introduce some uncertainties, so the International Atomic Energy Agency (IAEA) advises that each laboratory elaborates your own dose-response curve for cytogenetic dosimetry. The results were obtained from peripheral blood lymphocytes of the healthy and no-smoking donors exposed to 60Co and 137Cs radiation, with dose rate of 5 cGy.min.-1. Six points of dose were determined 20,50,100,200,300,400 cGy and the control not irradiated. The analysed aberrations were of chromosomic type, dicentric and centric ring. The dose response curve for dicentrics were obtained by frequencies weighted in liner-quadratic mathematic model and the equation resulted were for 60Co: Y = (3 46 +- 2.14)10-4 cGy-1 + (3.45 +- 0

  17. Biological Stress Response Terminology: Integrating the Concepts of Adaptive Response and Preconditioning Stress Within a Hormetic Dose-Response Framework

    Science.gov (United States)

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stres...

  18. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  19. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  20. Dose-response effects of fluoride in mammalian species

    International Nuclear Information System (INIS)

    A number of deleterious effects have been attributed to the ingestion of fluoride, sometimes for good reason and sometimes with no good basis. Literature describing some of these effects has been reviewed and threshold doses for the effects are suggested. Fluoride absorbed into the systemic circulation is rapidly removed, in part by storage in the skeletal system and in part by excretion in the urine. Skeletal storage evident in x-ray films as increased density to the x-rays is seen in about 10% of persons who have used drinking water containing 8 mg F per liter (8 ppm) for long periods of time. No deleterious effects are seen at this level of F storage in the bone. In the kidney the renal status of a population using water containing 8 mg F was not different from that of a population in an area where there was 0.4 ppm F in the water supply. Decreased renal function has been reported in persons using water supplies containing 10 ppm F. In human subjects growth is unaffected by prolonged use of water supplies containing up to 6-8 mg F/l (6-8 ppm). Growth in most animal species is not affected at concentrations of 100 mg F/kg diet (100 ppm). However, cattle undergoing cycle pregnancy, gestation and lactation appear to be more sensitive and growth is adversely affected at more than 40 ppm F in the diet. For cardiovascular effects, prolonged use of a water supply containing 2.5 mg F/l (2.5 ppm) was found not to increase the incidence of CVD

  1. The peripheral vascular effects of diltiazem--dose-response characteristics.

    OpenAIRE

    Finch, M B; Johnston, G D

    1985-01-01

    The acute effects of increasing doses of diltiazem on peripheral blood flow were observed in six subjects. Each subject received, in random order, a single oral dose of placebo or diltiazem 60, 120 or 180 mg. Supine heart rate, blood pressure, skin temperature, digital systolic pressure, forearm and digital blood flow were recorded before and at 1, 2, 3, 4 and 6 h post-dosing. Plasma diltiazem concentrations were measured at each time interval and at 12 and 24 h after the 120 mg dose. At dose...

  2. Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity

    NARCIS (Netherlands)

    Imre, G; Fokkema, DS; Den Boer, JA; Ter Horst, GJ

    2006-01-01

    The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PP1), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined

  3. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    Science.gov (United States)

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  4. Fundamental studies on the radiation chemical dose-response with use of thymine. Is activation of the surface between radiation biology and radiation chemistry possible?

    International Nuclear Information System (INIS)

    The review described the importance and difficulty of radiation chemical assessment of dose-response. The assessment has the tasks of the unit, low dose region evaluation and direct/indirect effects in biology. The authors' vacuum evaporated thymine for G-value determination is appropriate for XANES (X-ray absorption near edge structures) measurement with monochromic ultrasoft X-rays (-550 eV photon) generated by SPring-8. However, the data of yielded thymine derivatives as well as those yielded after 60Co γ-ray (1.5 MeV photon) irradiation are not suitable for direct application in DNA damage evaluation of living cells due to trans-scientific uncertainty. Efforts are required for reducing the uncertainty present in dose-response assessment. (K.H.)

  5. Dose-response effects of gamma irradiation on colour and antioxidant activity of wild Malva neglecta

    OpenAIRE

    Pinela, José; Antonio, Amilcar L.; Barros, Lillian; Carvalho, Ana Maria; Oliveira, M.B.P.P.; Ferreira, Isabel C. F. R.

    2014-01-01

    Radiation processing technology has been used to improve food security, safety and quality. However there are a few reports in the literature on the effect of irradiation on bioactivity of herbs and medicinal plants [1]. Hence, the present work was undertaken to investigate the dose-response effects of gamma irradiation on the colour and antioxidant activity of wild Malva neglecta Wallr. In the north-eastern of Portugal, this annual herbaceous plant is traditionally eaten raw as leafy vegetab...

  6. Dose-response regressions for algal growth and similar continuous endpoints: Calculation of effective concentrations

    DEFF Research Database (Denmark)

    Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels

    2009-01-01

    We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50......% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4......-4-(trifluoromethyl)phenoxy-phenol) with ranges of representative slopes at 50% response (0.54-2.62) and EC50s (2.20-357 mg/L) were selected. Reference EC50s and EC10s with 95% confidence limits using probit or Weibull models are calculated by nonlinear regression on the whole dataset using a dose - response...

  7. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+ 、 N+( 20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased withthe increase in dose and then increased in the high dose range and finally decreased again in thehigher dose range. Our experimental results suggest that D. radiodurans, which is considerablyradio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  8. Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review

    International Nuclear Information System (INIS)

    Chronic arsenic (As) poisoning has become a worldwide public health issue. Most human As exposure occurs from consumption of drinking water containing high amounts of inorganic As (iAs). In this paper, epidemiological studies conducted on the dose-response relationships between iAs exposure via the drinking water and related adverse health effects are reviewed. Before the review, the methods for evaluation of the individual As exposure are summarized and classified into two types, that is, the methods depending on As concentration of the drinking water and the methods depending on biological monitoring for As exposure; certain methods may be applied as optimum As exposure indexes to study dose-response relationship based on various As exposure situation. Chronic effects of iAs exposure via drinking water include skin lesions, neurological effects, hypertension, peripheral vascular disease, cardiovascular disease, respiratory disease, diabetes mellitus, and malignancies including skin cancer. The skin is quite sensitive to arsenic, and skin lesions are some of the most common and earliest nonmalignant effects related to chronic As exposure. The increase of prevalence in the skin lesions has been observed even at the exposure levels in the range of 0.005-0.01 mg/l As in drinking waters. Skin, lung, bladder, kidney, liver, and uterus are considered as sites As-induced malignancies, and the skin is though to be perhaps the most sensitive site. Prospective studies in large area of endemic As poisoning, like Bangladesh or China, where the rate of malignancies is expected to increase within the next several decades, will help to clarify the dose-response relationship between As exposure levels and adverse health effects with enhanced accuracy

  9. Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis

    DEFF Research Database (Denmark)

    Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens Einar;

    2015-01-01

    BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk of...... control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p<0.01). The risk of psychosis increased two and a half times for each additional adversity. All......-clinical control persons matched by gender, age and parents' socio-economic status. Assessment included the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Eighty-nine percent of the FEP group reported one or more adversities compared to 37% of the...

  10. Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Ellegaard-Jensen, Lea; Jensen, Keld Alstrup; Johansen, Anders

    2012-06-01

    Toxicity of nano-formulated silver to eukaryotes was assessed by exposing nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs): with average primary particle diameters of 1 nm (AgNP1) and 28nm (AgNP28, PVP coated), respectively. Tests were performed with and without presence of Escherichia coli to evaluate how the presence of a food bacterium affects the AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre-exposed to 0 and 1mgAgNPL(-1), respectively, for 20 h prior to exposure at higher concentrations of AgNP. Both AgNP1 and AgNP28 showed adverse dose-response effects and mortality on C. elegans. LC(50) for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coli in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when bacteria were not present. Pre-exposure to a low-level AgNP1 concentration made the nematodes slightly more sensitive to further exposure at higher concentrations compared to no pre-exposure, indicating that nematodes have no efficient physiological ability to counteract nano-silver toxicity by acclimation. The amount of dissolved Ag(+) was 0.18 to 0.21 mg L(-1) after 20 h at the highest AgNP1 (10 mg L(-1)) and AgNP28 (3 mg L(-1)) doses in the exposure medium, respectively. The upper limit of Ag(+) solubility cannot immediately explain the dose-response-related toxic effects of the AgNP nor the difference between AgNP1 and AgNP28. Higher toxicity of AgNP28 than AgNP1 may be explained by a combination of effects of coating, Ag-solubility and higher uptake rates due to agglomeration into μm-size agglomerates in the exposure medium. PMID:22475389

  11. Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Ellegaard-Jensen, Lea; Alstrup Jensen, Keld; Johansen, Anders

    2012-01-01

    presence of Escherichia coil to evaluate how the presence of a food bacterium affects the AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre-exposed to 0 and 1 mg AgNP L-1, respectively, for 20 h prior to exposure at higher concentrations of AgNP. Both AgNP1 and AgNP28 showed...... adverse dose-response effects and mortality on C. elegans. LC50 for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coil in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when...... AgNP1 and AgNP28. Higher toxicity of AgNP28 than AgNP1 may be explained by a combination of effects of coating, Ag-solubility and higher uptake rates due to agglomeration into mu m-size agglomerates in the exposure medium. (C) 2012 Elsevier Inc. All rights reserved....

  12. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

    Science.gov (United States)

    Urbain, Paul; Jakobsen, Jette

    2015-09-23

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon. PMID:26314311

  13. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms

    DEFF Research Database (Denmark)

    Urbain, Paul; Jakobsen, Jette

    2015-01-01

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour...... of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered...... a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P mushrooms and comparable to levels found...

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

    International Nuclear Information System (INIS)

    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)

  15. Effect of Relative Humidity on Dose Response of Effervescent Glycine Pellet Dosimeters

    Directory of Open Access Journals (Sweden)

    Santosh H Shinde

    2013-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Glycine pellet dosimeter based on spectrophotometric read-out method has a useful dose range of 100 to 1000 Gy and is apt for routine dosimetry in low dose applications of radiation processing. The read-out method requires dissolution of these pellets in acidified solution of ferrous ammonium sulphate and xylenol orange, but due to appreciable hardness of these pellets it is required to stir the solution for complete dissolution which is generally not preferable. Hence fast dissolving pellets were fabricated using sodium bicarbonate as an effervescent agent. As sodium bicarbonate is hygroscopic, study of effect of relative humidity on dose response of these pellets was carried out in the present work.  

  16. The effects of heating rate on the dose response characteristics of CaF2 :Dy (TLD-200)

    International Nuclear Information System (INIS)

    In this study; the effects of heating rates (1 degree C/s and 10 degree C/s) on the dose response characteristics of low temperature peaks, LTPs, (30 degree C - 250 degree C) and high temperature peaks, HTPs, (260 degree C- 600 degree C) of CaF2:Dy (TLD-200) crystal has been investigated using the dose dependence curve and dose response function f(D). The samples were obtained from Harshaw Chemical Company, Ohio, USA. All irradiations were performed immediately after the standard annealing at 500 degree C for 1 hour at room temperature with β rays from a 90Sr- 90Y source (∼0.04 Gy/s). Glow curves were obtained using a Harshaw QS 3500 Manuel type reader. The results of the experiments have shown that the linearity and behavior of the TL glow peaks of TLD-200 are affected from the heating rate.

  17. QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

    Science.gov (United States)

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. PMID:26812258

  18. Comparison of effects of six tritiated compounds on chromosomal aberrations in human lymphocytes in vitro and dose-response relationships

    International Nuclear Information System (INIS)

    The effects of six tritiated compounds on chromosomal aberrations were compared in cultured human lymphocytes, and dose-response relationships were analysed. According to the efficiency of inducing aberrations, these compounds could be arranged in decreasing order as follows: 3H-TdR > 3H-UdR > 3H-lysine > 3H-thymine > 3H-leucine > HTO, when the dose-response relationship was expressed in radioactivity/ml of the medium. This order is determined mainly by the radioactivities incorporated into the nuclei or the cells. However, when compared in terms of the dose absorbed by the nuclei or the cells, the differences among various compounds would be much more reduced. The data of aberration yields for different tritium activities (or absorbed dsoes) were fitted satisfactorily to the linear-quadratic dose-response equation Y = A + BX + CX2. The yields of chromatid-type and chromosometype aberrations induced by various tritiated compounds were quite different. These differences are related to the metabolism of the compounds

  19. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    DEFF Research Database (Denmark)

    Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas;

    2013-01-01

    A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted of lectu...... consensus was reached the robust discussions were helpful to inform both basic scientists and risk assessors on all the issues. There were a number of important ideas developed to help continue the discussion and improve communication over the next few years....

  20. Low dose radiation induced adaptive response upon salt stress and vacuum stress: a possible mechanism for the effect of saddle-like dose response curve

    International Nuclear Information System (INIS)

    To explore mechanism for the effect of saddle-like dose-response curve, the relationship of irradiation-vacuum stress, and irradiation-salt stress, was investigated with rice seeds irradiated to 60-560 Gy by 60Co γ-rays. The dose-response curve was simulated based on seedling height data, which showed obedient to linear-quadratic model. During germination,the irradiated rice seeds were stressed by 10-3 Pa vacuum, or by NaCl in different concentrations. After that, the dose-response curve manifested a saddle-like shape. The results indicate that while low dose irradiation could retard seedling growth synergistically with vacuum stress and salt stress, it could also induce adaptive response upon vacuum stress and salt stress. Low dose irradiation induced adaptive response upon environmental adverse factors could contribute to the mechanism for the effect of saddle-like dose-response curve. (authors)

  1. Effects of measurement strategy and statistical analysis on dose-response relations between physical workload and low back pain

    NARCIS (Netherlands)

    J.J.P. Jansen (Justin); A. Burdorf (Alex)

    2003-01-01

    textabstractBACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To evaluat

  2. Dose response relationship and Alara

    International Nuclear Information System (INIS)

    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

  3. Dose response of ferrous-xylenol orange gels: the effects of gel substrate, gelation time and dose fractionation

    Science.gov (United States)

    Jordan, K.; Battista, J.

    2004-01-01

    Investigations of the dose dependent change in optical transmission, dose response, for radiochromic ferrous-xylenol orange-gelatin gels (FXG) 3D optical CT scanning has revealed that gelation time, temperature, and dose fractionation affect the dose response (Δμ/Δdose). Correction for these factors is important for developing a reproducible dosimeter that can be reliably calibrated and used clinically. The purpose of this report is to examine trends in dose response changes for the following parameters: gelation time-temperature, concentrations of ferrous ion and xylenol orange (XO), dose range and dose fractionation.

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

    DEFF Research Database (Denmark)

    Kjellström, Tord; Grandjean, Philippe

    2007-01-01

    Toxic Effects of Metals Aluminum Antimony Arsenic Barium Beryllium Bismuth Cadmium Chromium Cobalt Copper Gallium and Semiconductor Compounds Germanium Indium Iron Lead Manganese Mercury Molybdenum Nickel Palladium Platinum Selenium Silver Tellurium Thallium Tin Titanium Tungsten Uranium Vanadium Zinc...

  5. Analysis of bias effects on the total ionizing dose response in a 180 nm technology

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhangli, E-mail: liuzhangli@mail.sim.ac.cn [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Hu Zhiyuan [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Zhang, Zhengxuan; Shao Hua [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Chen Ming [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Bi Dawei [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Ning Bingxu [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Zou Shichang [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China)

    2011-07-11

    The effects of gamma ray irradiation on the shallow trench isolation (STI) leakage current in a 180 nm technology are investigated. The radiation response is strongly influenced by the bias modes, gate bias during irradiation, substrate bias during irradiation and operating substrate bias after irradiation. We found that the worst case occurs under the ON bias condition for the ON, OFF and PASS bias mode. A positive gate bias during irradiation significantly enhances the STI leakage current, indicating the electric field influence on the charge buildup process during radiation. Also, a negative substrate bias during irradiation enhances the STI leakage current. However a negative operating substrate bias effectively suppresses the STI leakage current, and can be used to eliminate the leakage current produced by the charge trapped in the deep STI oxide. Appropriate substrate bias should be introduced to alleviate the total ionizing dose (TID) response, and lead to acceptable threshold voltage shift and subthreshold hump effect. Depending on the simulation results, we believe that the electric field distribution in the STI oxide is the key parameter influencing bias effects on the radiation response of transistor. - Highlights: > ON bias is the worst bias condition for the ON, PASS and OFF bias modes. > Larger gate bias during irradiation leads to more pronounced characteristic degradation. > TID induced STI leakage can be suppressed by negative operating substrate bias voltage. > Negative substrate bias during irradiation leads to larger increase of off-state leakage. > Electric field in the STI oxide greatly influences the device's radiation effect.

  6. Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: Evidence for the prolonged effects of radiation on the thyroid

    International Nuclear Information System (INIS)

    The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. The authors have identified 4,296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3,843 subjects. Of the 2,634 subjects who have been found, 1,043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose-response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodules within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and the screening program, which began in 1974, the authors compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose-response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr

  7. Analysis of bias effects on the total ionizing dose response in a 180 nm technology

    Science.gov (United States)

    Liu, Zhangli; Hu, Zhiyuan; Zhang, Zhengxuan; Shao, Hua; Chen, Ming; Bi, Dawei; Ning, Bingxu; Zou, Shichang

    2011-07-01

    The effects of gamma ray irradiation on the shallow trench isolation (STI) leakage current in a 180 nm technology are investigated. The radiation response is strongly influenced by the bias modes, gate bias during irradiation, substrate bias during irradiation and operating substrate bias after irradiation. We found that the worst case occurs under the ON bias condition for the ON, OFF and PASS bias mode. A positive gate bias during irradiation significantly enhances the STI leakage current, indicating the electric field influence on the charge buildup process during radiation. Also, a negative substrate bias during irradiation enhances the STI leakage current. However a negative operating substrate bias effectively suppresses the STI leakage current, and can be used to eliminate the leakage current produced by the charge trapped in the deep STI oxide. Appropriate substrate bias should be introduced to alleviate the total ionizing dose (TID) response, and lead to acceptable threshold voltage shift and subthreshold hump effect. Depending on the simulation results, we believe that the electric field distribution in the STI oxide is the key parameter influencing bias effects on the radiation response of transistor.

  8. Detector dose response in megavoltage small photon beams. II. Pencil beam perturbation effects

    International Nuclear Information System (INIS)

    Purpose: To quantify detector perturbation effects in megavoltage small photon fields and support the theoretical explanation on the nature of quality correction factors in these conditions. Methods: In this second paper, a modern approach to radiation dosimetry is defined for any detector and applied to small photon fields. Fano’s theorem is adapted in the form of a cavity theory and applied in the context of nonstandard beams to express four main effects in the form of perturbation factors. The pencil-beam decomposition method is detailed and adapted to the calculation of perturbation factors and quality correction factors. The approach defines a perturbation function which, for a given field size or beam modulation, entirely determines these dosimetric factors. Monte Carlo calculations are performed in different cavity sizes for different detection materials, electron densities, and extracameral components. Results: Perturbation effects are detailed with calculated perturbation functions, showing the relative magnitude of the effects as well as the geometrical extent to which collimating or modulating the beam impacts the dosimetric factors. The existence of a perturbation zone around the detector cavity is demonstrated and the approach is discussed and linked to previous approaches in the literature to determine critical field sizes. Conclusions: Monte Carlo simulations are valuable to describe pencil beam perturbation effects and detail the nature of dosimetric factors in megavoltage small photon fields. In practice, it is shown that dosimetric factors could be avoided if the field size remains larger than the detector perturbation zone. However, given a detector and beam quality, a full account for the detector geometry is necessary to determine critical field sizes

  9. Detector dose response in megavoltage small photon beams. II. Pencil beam perturbation effects

    Energy Technology Data Exchange (ETDEWEB)

    Bouchard, Hugo, E-mail: hugo.bouchard@npl.co.uk; Duane, Simon [Acoustics and Ionising Radiation Team, National Physical Laboratory, Hampton Road, Teddington TW11 0LW (United Kingdom); Kamio, Yuji [Centre hospitalier de l’Université de Montréal (CHUM), 1560 Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada); Palmans, Hugo [Acoustics and Ionising Radiation Team, National Physical Laboratory, Hampton Road, Teddington TW11 0LW (United Kingdom); Medical Physics, EBG MedAustron GmbH, Wiener Neustadt A-2700 (Austria); Seuntjens, Jan [Medical Physics Unit, McGill University, Montréal, Québec H3G 1A4 (Canada)

    2015-10-15

    Purpose: To quantify detector perturbation effects in megavoltage small photon fields and support the theoretical explanation on the nature of quality correction factors in these conditions. Methods: In this second paper, a modern approach to radiation dosimetry is defined for any detector and applied to small photon fields. Fano’s theorem is adapted in the form of a cavity theory and applied in the context of nonstandard beams to express four main effects in the form of perturbation factors. The pencil-beam decomposition method is detailed and adapted to the calculation of perturbation factors and quality correction factors. The approach defines a perturbation function which, for a given field size or beam modulation, entirely determines these dosimetric factors. Monte Carlo calculations are performed in different cavity sizes for different detection materials, electron densities, and extracameral components. Results: Perturbation effects are detailed with calculated perturbation functions, showing the relative magnitude of the effects as well as the geometrical extent to which collimating or modulating the beam impacts the dosimetric factors. The existence of a perturbation zone around the detector cavity is demonstrated and the approach is discussed and linked to previous approaches in the literature to determine critical field sizes. Conclusions: Monte Carlo simulations are valuable to describe pencil beam perturbation effects and detail the nature of dosimetric factors in megavoltage small photon fields. In practice, it is shown that dosimetric factors could be avoided if the field size remains larger than the detector perturbation zone. However, given a detector and beam quality, a full account for the detector geometry is necessary to determine critical field sizes.

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

    International Nuclear Information System (INIS)

    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

  11. Chronic exposure to odorous chemicals in residential areas and effects on human psychosocial health: dose-response relationships.

    Science.gov (United States)

    Blanes-Vidal, Victoria; Bælum, Jesper; Nadimi, Esmaeil S; Løfstrøm, Per; Christensen, Lars P

    2014-08-15

    Perceived air pollution, including environmental odor pollution, is known to be an environmental stressor that affects individuals' psychosocial health and well-being. However, very few studies have been able to quantify exposure-response associations based on individual-specific residential exposures to a proxy gas and to examine the mechanisms underlying these associations. In this study, individual-specific exposures in non-urban residential environments during 2005-2010 on a gas released from animal biodegradable wastes (ammonia, NH3) were calculated by the Danish Eulerian long-range transport model and the local-scale transport deposition model. We used binomial and multinomial logistic regression and mediation analyses to examine the associations between average exposures and questionnaire-based data on psychosocial responses, after controlling for person-specific covariates. About 45% of the respondents were annoyed by residential odor pollution. Exposures were associated with annoyance (adjusted odds ratio [ORadj]=3.54, 95% confidence interval [CI]=2.33-5.39), health risk perception (ORadj=4.94; 95% CI=1.95-12.5) and behavioral interference (ORadj=3.28; 95% CI=1.77-6.11), for each unit increase in loge(NH3 exposure). Annoyance was a strong mediator in exposure-behavior interference and exposure-health risk perception relationships (81% and 44% mediation, respectively). Health risk perception did not play a mediating role in exposure-annoyance or exposure-behavioral interference relationships. This is the first study to provide a quantitative estimation of the dose-response associations between ambient NH3 exposures and psychosocial effects caused by odor pollution in non-urban residential outdoor environments. It further shows that these effects are both direct and mediated by other psychosocial responses. The results support the use of NH3 as a proxy gas of air pollution from animal biodegradable wastes in epidemiologic studies. PMID:24880544

  12. Effects of the pre-irradiation storage procedure on the dose response of a Fricke xylenol orange gel dosimeter

    Directory of Open Access Journals (Sweden)

    Liosi Giulia Maria

    2015-09-01

    Full Text Available The Fricke xylenol orange (FX gel system is a chemical dosimeter characterized by good sensitivity, linear dose response, tissue equivalence, no toxicity, easy preparation, reproducibility and low cost. Thanks to the presence of the gelatinous matrix, the system is particularly suitable to perform reliable 3D mapping of the absorbed dose spatial distribution via magnetic resonance imaging (MRI or optical techniques. The aim of this work is to study in a systematic way the influence of the pre-irradiation storage procedure upon sensitivity, dose response stability and lifetime of use of a FX gel system made with gelatin from porcine skin subjected to homogeneous irradiation. For this purpose, different pre-irradiation storage procedures, in terms of temperature and duration of each storage step, were investigated. In order to evaluate the dose response stability, the optical analyses of the samples were performed up to 6 hours after irradiation. Moreover, the samples were irradiated at time intervals of 24 hours for up to 7 days after preparation in order to evaluate the system lifetime of use. Regardless of their thermal and temporal life, the samples show linear dose responses in the investigated dose range (3-24 Gy and an increase of sensitivity with the time elapsed between preparation and irradiation. Among the three pre-irradiation storage procedures considered here, a procedure that provides the best dose response stability and lifetime of use was identified and recommended for further use. The analyzed dosimetric system possesses good properties that make it promising for medical application, particularly concerning the evaluation of pre-treatment plan quality assurance within the conformational external beam radiotherapy

  13. Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid.

    Science.gov (United States)

    Weterings, Peter J J M; Loftus, Christine; Lewandowski, Thomas A

    2016-08-22

    Potential adverse effects of chemical substances on thyroid function are usually examined by measuring serum levels of thyroid-related hormones. Instead, recent risk assessments for thyroid-active chemicals have focussed on iodine uptake inhibition, an upstream event that by itself is not necessarily adverse. Establishing the extent of uptake inhibition that can be considered de minimis, the chosen benchmark response (BMR), is therefore critical. The BMR values selected by two international advisory bodies were 5% and 50%, a difference that had correspondingly large impacts on the estimated risks and health-based guidance values that were established. Potential treatment-related inhibition of thyroidal iodine uptake is usually determined by comparing thyroidal uptake of radioactive iodine (RAIU) during treatment with a single pre-treatment RAIU value. In the present study it is demonstrated that the physiological intra-individual variation in iodine uptake is much larger than 5%. Consequently, in-treatment RAIU values, expressed as a percentage of the pre-treatment value, have an inherent variation, that needs to be considered when conducting dose-response analyses. Based on statistical and biological considerations, a BMR of 20% is proposed for benchmark dose analysis of human thyroidal iodine uptake data, to take the inherent variation in relative RAIU data into account. Implications for the tolerated daily intakes for perchlorate and chlorate, recently established by the European Food Safety Authority (EFSA), are discussed. PMID:27268963

  14. Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, Peter [University of Oxford; Anderson, Jennifer [University of Oxford

    2014-10-02

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGFβ pathways initiated by low and high LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  15. Biological effects of inhaled radionuclides

    International Nuclear Information System (INIS)

    This report focuses on various types of radionuclides that may be inhaled and deposited in the respiratory tract. One of the primary goals of this ICRP Task Group is to assess specifically the biological implications of inhaled plutonium. Because other transuranics are becoming more abundant, information on americium, curium and einsteinium is included. Data are also included from studies of polonium and of several beta-gamma emitting isotopes. The Task Group evaluated most of the data on the biological effects of inhaled radionuclides in experimental animals to identify the tissues at risk and to assess possible dose-response relationships. Few data from human cases of inhaled radionuclides are available for this assessment. The biological effects of nonradioactive air pollutants were also considered to provide the perspective that all air pollutants can have a deleterious effect on human life and to emphasize the possibility for combined or synergistic effects of nonradioactive and radioactive substances on the respiratory tract. (orig./HP)

  16. Antidepressant treatments: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex.

    OpenAIRE

    Green, A. R.; Heal, D. J.; Johnson, P.; Laurence, B. E.; Nimgaonkar, V. L.

    1983-01-01

    The effects of repeated electroconvulsive shock (ECS) administration, repeated desmethylimipramine injection (5 mg kg-1, twice daily for 14 days) and acute administration of the beta-adrenoceptor, clenbuterol, on 5-hydroxytryptamine (5-HT)- and dopamine-mediated behaviours in mice have been examined. All three treatments enhanced the carbidopa/5-hydroxytryptophan (5-HTP)-induced head-twitch response at all doses of 5-HTP examined, producing a parallel shift in the dose-response curve. A singl...

  17. A Bayesian Semiparametric Model for Radiation Dose-Response Estimation.

    Science.gov (United States)

    Furukawa, Kyoji; Misumi, Munechika; Cologne, John B; Cullings, Harry M

    2016-06-01

    In evaluating the risk of exposure to health hazards, characterizing the dose-response relationship and estimating acceptable exposure levels are the primary goals. In analyses of health risks associated with exposure to ionizing radiation, while there is a clear agreement that moderate to high radiation doses cause harmful effects in humans, little has been known about the possible biological effects at low doses, for example, below 0.1 Gy, which is the dose range relevant to most radiation exposures of concern today. A conventional approach to radiation dose-response estimation based on simple parametric forms, such as the linear nonthreshold model, can be misleading in evaluating the risk and, in particular, its uncertainty at low doses. As an alternative approach, we consider a Bayesian semiparametric model that has a connected piece-wise-linear dose-response function with prior distributions having an autoregressive structure among the random slope coefficients defined over closely spaced dose categories. With a simulation study and application to analysis of cancer incidence data among Japanese atomic bomb survivors, we show that this approach can produce smooth and flexible dose-response estimation while reasonably handling the risk uncertainty at low doses and elsewhere. With relatively few assumptions and modeling options to be made by the analyst, the method can be particularly useful in assessing risks associated with low-dose radiation exposures. PMID:26581473

  18. Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.

    Science.gov (United States)

    Cai, Hong; Scott, Edwina; Kholghi, Abeer; Andreadi, Catherine; Rufini, Alessandro; Karmokar, Ankur; Britton, Robert G; Horner-Glister, Emma; Greaves, Peter; Jawad, Dhafer; James, Mark; Howells, Lynne; Ognibene, Ted; Malfatti, Michael; Goldring, Christopher; Kitteringham, Neil; Walsh, Joanne; Viskaduraki, Maria; West, Kevin; Miller, Andrew; Hemingway, David; Steward, William P; Gescher, Andreas J; Brown, Karen

    2015-07-29

    Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [(14)C]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention. PMID:26223300

  19. Biological effects

    International Nuclear Information System (INIS)

    Following an introduction into the field of cellular radiation effect considering the most important experimental results, the biological significance of the colony formation ability is brought out. The inactivation concept of stem cells does not only prove to be good, according to the present results, in the interpretation of the pathogenesis of acute radiation effects on moult tissue, it also enables chronicle radiation injuries to be interpreted through changes in the fibrous part of the organs. Radiation therapy of tumours can also be explained to a large extent by the radiation effect on the unlimited reproductiveness of tumour cells. The more or less similar dose effect curves for healthy and tumour tissue in practice lead to intermittent irradiation. The dependence of the intermittent doses and intervals on factors such as Elkind recovery, synchronisation, redistribution, reoxygenation, repopulation and regeneration are reviewed. (ORU/LH)

  20. Implicit dose-response curves.

    Science.gov (United States)

    Pérez Millán, Mercedes; Dickenstein, Alicia

    2015-06-01

    We develop tools from computational algebraic geometry for the study of steady state features of autonomous polynomial dynamical systems via elimination of variables. In particular, we obtain nontrivial bounds for the steady state concentration of a given species in biochemical reaction networks with mass-action kinetics. This species is understood as the output of the network and we thus bound the maximal response of the system. The improved bounds give smaller starting boxes to launch numerical methods. We apply our results to the sequential enzymatic network studied in Markevich et al. (J Cell Biol 164(3):353-359, 2004) to find nontrivial upper bounds for the different substrate concentrations at steady state. Our approach does not require any simulation, analytical expression to describe the output in terms of the input, or the absence of multistationarity. Instead, we show how to extract information from effectively computable implicit dose-response curves, with the use of resultants and discriminants. We moreover illustrate in the application to an enzymatic network, the relation between the exact implicit dose-response curve we obtain symbolically and the standard hysteresis diagram provided by a numerical ode solver. The setting and tools we propose could yield many other results adapted to any autonomous polynomial dynamical system, beyond those where it is possible to get explicit expressions. PMID:25008963

  1. Radiation Dose-Response Relationships and Risk Assessment

    International Nuclear Information System (INIS)

    The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is presented

  2. Biological transformation, kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

    Institute of Scientific and Technical Information of China (English)

    M A Mottaleb; J H Zimmerman; T W Moy

    2008-01-01

    Low levels (ng/g) of musk ketone (MK), used as a fragrance additive in the formulation of personal care products, are frequently detected in the water and other environment. Thus, aquatic organisms can be continuously exposed to MK. In this study, kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite, bound to cysteine-hemoglobin (Hb) in rainbow trout, formed by enzymatic nitro-reduction of MK have been demonstrated. Trout were exposed to a single exposure of 0.010, 0.030, 0.10, and or 0.30 mg MK/g of fish. Twenty-six Hb samples were collected from exposed- and control fish subsequent to exposure intervals of 1 d (24 h), 3 d (72 h), and 7 d (168 h). Basic hydrolysis released bound AMK metabolite was extracted into n-hexane and then concentrated and analyzed by gas chromatography (GC) electron capture negative ion chemical ionization (NICI) mass spectrometry (MS) using selected ion monitoring (SIM). The presence of the AMK metabolite in Hb extracts was confirmed by agreement of similar mass spectral features and retention time with a standard. In the dose-response study, maximum adduct formation was obtained at the 0.10 mg/g dose with an average AMK metabolite concentration of 2.2 ng/g. For kinetics, the highest concentration of the AMK metabolite was found to be 32.0 ng/g at 0.03 mg/g dose in 3-d sample. Further elimination of the metabolite showed kinetics with a half-life estimated to be 2 d, assuming first-order kinetics. The metabolite was not detected in the control samples, non-hydrolyzed Hb, and reagent blank extracts. The detection limit for AMK in the Hb was approximately 0.30 (g/L, based on a signal to noise ratio of 3 (S/N = 3).

  3. Application of environmental dose-response models to epidemiology and animal data for the effects of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Cothern, C.R. (Environmental Protection Agency, Washington, DC (USA)); Crawford-Brown, D.J. (Univ. of North Carolina, Chapel Hill (USA)); Wrenn, M.E. (Environmental Radiation and Toxicology Laboratory, Salt Lake City, UT (USA))

    1990-01-01

    Previous extrapolations of risk from exposure to radiation at low levels (such as environmental exposures) have focused on various empirical models that have some axiomatic base, sometimes called state-vector models and usually involving linear and quadratic functions. Such models are based on representations of the physical processes occurring in irradiated cells, but do not include consideration of biological factors that could cause variability in biological response. Some mathematical models employed in environmental risk assessments (such statistically based models as the multistage, logit, probit, and Weibull) reverse this problem, showing little axiomatic support but incorporating variability, although this is not biological variability at doses of interest here. This paper presents the results of the predictions of these latter models as they apply to environmental levels of exposure to ionizing radiation compared to the estimates made by the more commonly used models. The study involves analysis of data from hard rock miner exposure to radon, exposure of rats to radon, the ingestion of radium by watch dial painters and beagle dogs, and the exposure of Japanese citizens to atomic bomb explosions. These results then are compared with inferences obtained using the more conventional axiomatic models, such as the linear/quadratic models. It is demonstrated that the results are similar, providing partial evidence that current ranges placed on risk estimates are not altered much by the selection of a particular class of models for use in quantitative risk assessment and uncertainty analysis. (Ranges are dependent on how far the data is to be extrapolated).

  4. Biological effects of radiation

    International Nuclear Information System (INIS)

    This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

  5. Effect of Carotene and Lycopene on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

    Directory of Open Access Journals (Sweden)

    Yulan Wang

    Full Text Available Many epidemiologic studies have investigated the association between carotenoids intake and risk of Prostate cancer (PCa. However, results have been inconclusive.We conducted a systematic review and dose-response meta-analysis of dietary intake or blood concentrations of carotenoids in relation to PCa risk. We summarized the data from 34 eligible studies (10 cohort, 11 nested case-control and 13 case-control studies and estimated summary Risk Ratios (RRs and 95% confidence intervals (CIs using random-effects models.Neither dietary β-carotene intake nor its blood levels was associated with reduced PCa risk. Dietary α-carotene intake and lycopene consumption (both dietary intake and its blood levels were all associated with reduced risk of PCa (RR for dietary α-carotene intake: 0.87, 95%CI: 0.76-0.99; RR for dietary lycopene intake: 0.86, 95%CI: 0.75-0.98; RR for blood lycopene levels: 0.81, 95%CI: 0.69-0.96. However, neither blood α-carotene levels nor blood lycopene levels could reduce the risk of advanced PCa. Dose-response analysis indicated that risk of PCa was reduced by 2% per 0.2mg/day (95%CI: 0.96-0.99 increment of dietary α-carotene intake or 3% per 1mg/day (95%CI: 0.94-0.99 increment of dietary lycopene intake.α-carotene and lycopene, but not β-carotene, were inversely associated with the risk of PCa. However, both α-carotene and lycopene could not lower the risk of advanced PCa.

  6. Acute toxicity of methyl isocyanate: a preliminary study of the dose response for eye and other effects.

    Science.gov (United States)

    Salmon, A G; Kerr Muir, M; Andersson, N

    1985-12-01

    Acute toxic effects of methyl isocyanate in the rat were determined for two hour exposures to concentrations in the range 11 ppm (very slight effect) to 65 ppm (lethality: pulmonary oedema). Changes in the eye, lungs, and behaviour were noted. Eye changes were confined to erosions of the corneal epithelium and were most severe at intermediate levels of exposure. A comparison was made of the effects noted in rats with reported effects on survivors of the Bhopal disaster. Urinary thiocyanate concentrations in exposed rats were found to be reduced relative to control values. PMID:4074650

  7. Brain development in mice after prenatal irradiation: Modes of effect manifestation; dose-response-relationships and the RBE of neutrons

    International Nuclear Information System (INIS)

    Postnatal effect manifestation in the CNS after exposures during advanced prenatal stages of development is due to both the prolonged period of neurogenesis and its complexity. Apart from acute proliferative effects, examples of two types of long-term effects in the brains of prenatally exposed mice are represented. Namely, persistent structural damage, and, fluctuating responses during the histochemical and biochemical brain maturation. Structural effects following X-ray exposure are quantified on the basis of data for diameter diminution of the cortical plate, corpus callosum and fimbria hippocampi. The studies include computerized micro-videoanalysis of neuronal branching defects. Continuous extension of exposure levels to doses as low as 0.05 Gy give evidence for the existence of thresholds for these types of structural damage in the vicinity of exposures to 0.1 Gy. The effects following X-ray exposures are partly compared with corresponding effects after neutron exposures. Our studies on postnatal maturation disturbances include proliferative responses, myelin formation, as well as the determination of different biochemical parameters (ATP, myelin-proteins, Na+/K+-balance). From our experimental findings we are able to stress the special significance of neurogenetical long-term effects for risk estimates in man. (orig.)

  8. Dose responsive effects of subcutaneous pentosan polysulfate injection in mucopolysaccharidosis type VI rats and comparison to oral treatment.

    Directory of Open Access Journals (Sweden)

    Michael Frohbergh

    Full Text Available BACKGROUND: We previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS treatment in a rat model of mucopolysaccharidosis (MPS type VI. Herein we compare these effects to once weekly, subcutaneous (s.c. injection. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Injected PPS also effectively treats osteoarthritis in animals, and has shown success in osteoarthritis patients. METHODOLOGY/PRINCIPAL FINDINGS: One-month-old MPS VI rats were given once weekly s.c. injections of PPS (1, 2 and 4 mg/kg, human equivalent dose (HED, or daily oral PPS (4 mg/kg HED for 6 months. Serum inflammatory markers and total glycosaminoglycans (GAGs were measured, as were several histological, morphological and functional endpoints. Overall, weekly s.c. PPS injections led to similar or greater therapeutic effects as daily oral administration. Common findings between the two treatment approaches included reduced serum inflammatory markers, improved dentition and skull lengths, reduced tracheal deformities, and improved mobility. Enhanced effects of s.c. treatment included GAG reduction in urine and tissues, greater endurance on a rotarod, and better improvements in articular cartilage and bone in some dose groups. Optimal therapeutic effects were observed at 2 mg/kg, s.c.. No drug-related increases in liver enzymes, coagulation factor abnormalities or other adverse effects were identified following 6 months of s.c. PPS administration. CONCLUSIONS: Once weekly s.c. administration of PPS in MPS VI rats led to equal or better therapeutic effects than daily oral administration, including a surprising reduction in urine and tissue GAGs. No adverse effects from s.c. PPS administration were observed over the 6-month study period.

  9. Dose Responsive Effects of Subcutaneous Pentosan Polysulfate Injection in Mucopolysaccharidosis Type VI Rats and Comparison to Oral Treatment

    Science.gov (United States)

    Frohbergh, Michael; Ge, Yi; Meng, Fanli; Karabul, Nesrin; Solyom, Alexander; Lai, Alon; Iatridis, James; Schuchman, Edward H.; Simonaro, Calogera M.

    2014-01-01

    Background We previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS) treatment in a rat model of mucopolysaccharidosis (MPS) type VI. Herein we compare these effects to once weekly, subcutaneous (sc) injection. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Injected PPS also effectively treats osteoarthritis in animals, and has shown success in osteoarthritis patients. Methodology/Principal Findings One-month-old MPS VI rats were given once weekly sc injections of PPS (1, 2 and 4 mg/kg, human equivalent dose (HED)), or daily oral PPS (4 mg/kg HED) for 6 months. Serum inflammatory markers and total glycosaminoglycans (GAGs) were measured, as were several histological, morphological and functional endpoints. Overall, weekly sc PPS injections led to similar or greater therapeutic effects as daily oral administration. Common findings between the two treatment approaches included reduced serum inflammatory markers, improved dentition and skull lengths, reduced tracheal deformities, and improved mobility. Enhanced effects of sc treatment included GAG reduction in urine and tissues, greater endurance on a rotarod, and better improvements in articular cartilage and bone in some dose groups. Optimal therapeutic effects were observed at 2 mg/kg, sc. No drug-related increases in liver enzymes, coagulation factor abnormalities or other adverse effects were identified following 6 months of sc PPS administration. Conclusions Once weekly sc administration of PPS in MPS VI rats led to equal or better therapeutic effects than daily oral administration, including a surprising reduction in urine and tissue GAGs. No adverse effects from sc PPS administration were observed over the 6-month study period. PMID:24964042

  10. Effects of acute sublethal gamma radiation exposure on aggressive behavior in male mice: A dose-response study

    International Nuclear Information System (INIS)

    The resident-intruder paradigm was used to assess the effects of gamma radiation (0, 3, 5, 7 Gray [Gy] cobalt-60) on aggressive offensive behavior in resident male mice over a 3-month period. The defensive behavior of nonirradiated intruder mice was also monitored. A dose of 3 Gy had no effect on either the residents' offensive behavior or the defensive behavior of the intruders paired with them. Doses of 5 and 7 Gy produced decreases in offensive behavior of irradiated residents during the second week postirradiation. The nonirradiated intruders paired with these animals displayed decreases in defensive behavior during this time period, indicating a sensitivity to changes in the residents' behavior. After the third week postirradiation, offensive and defensive behavior did not differ significantly between irradiated mice and sham-irradiated controls. This study suggests that sublethal doses of radiation can temporarily suppress aggressive behavior but have no apparent permanent effect on that behavior

  11. Dose-response studies on promoting and anticarcinogenic effects of phenobarbital and DDT in the rat hepatocarcinogenesis.

    Science.gov (United States)

    Kitagawa, T; Hino, O; Nomura, K; Sugano, H

    1984-12-01

    Possible discrepancy between the dose level required for promoting action, when given after initiation process, and that needed to exert an anticarcinogenic effect when given simultaneously with a carcinogen, of hepatic promoters were investigated in an attempt to obtain a 'practical' threshold dose of promoters. Phenobarbital (PB) and dichlorophenyltrichloroethane (DDT) were used as promoters and 3'-methyl-4-(dimethylamino)-azobenzene (3'-Me-DAB) was used as the carcinogen. Male weanling rats were treated with 600 p.p.m. 3'-Me-DAB for 3 weeks followed by a diet containing a promoter at various dose levels (5-500 p.p.m.), or the animals were treated with a low dose (100 p.p.m.) of 3'-Me-DAB plus a promoter at various dose levels (20-500 p.p.m.). The effects of promoters were measured by scoring size and number of enzyme-altered islands at weeks 12 and 24 of rat age. The promoting effect of PB and DDT was demonstrated in dose-dependent fashion, in the dose range of 10-500 p.p.m. and 20-500 p.p.m., respectively. On the other hand, promoters given simultaneously with a low dose of carcinogen enhanced the carcinogenesis at all the dose levels tested, quite in contrast with their inhibitory effect on carcinogenesis when given together with relatively high doses of carcinogens. PMID:6499117

  12. Arsenic Disruption of Steroid Receptor Gene Activation: Complex Dose-Response Effects Are Shared by Several Steroid Receptors*

    Science.gov (United States)

    Bodwell, Jack E.; Gosse, Julie A.; Nomikos, Athena P.; Hamilton, Joshua W.

    2008-01-01

    Chronic intake of arsenic (As) has been associated with increased risk of cancer, diabetes, developmental and reproductive problems, and cardiovascular disease. Recent studies suggest increased health risks with drinking water levels as low as 5–10 ppb. We previously reported that As disrupts glucocorticoid receptor (GR) mediated transcription in a very complex fashion. Low As levels (0.1 to 0.7 μM) stimulated transcription whereas slightly higher levels (1 to 3 μM) were inhibitory. The DNA Binding Domain (DBD) was the minimal region of GR required for the response to As. Mutations in the DBD that alter the conformation of the dimerization domain (D-Loop) to a DNA-bound GR conformation abolished the stimulatory effect and enhanced the inhibitory response to As. Here we report that receptors for progesterone (PR) and mineralocorticoids (MR) display a similar complex As response as the GR, suggesting a common mechanism for this effect. The complex response to As is not due to altered steroid or receptor levels. Moreover, a well-characterized GR dimerization mutant displayed a wild-type biphasic response to As for several divergent reporter genes, suggesting that dimerization is not critical for the response to As. Fluorescence polarization studies with purified PR and GR demonstrated that the specific PR/GR-DNA interaction is not altered in the presence of As. These results indicate that the numerous and diverse human health effects associated with As exposure maybe mediated, at least in part, through its ability to simultaneously disrupt multiple hormone receptor systems. PMID:17173375

  13. Arsenic disruption of steroid receptor gene activation: Complex dose-response effects are shared by several steroid receptors.

    Science.gov (United States)

    Bodwell, Jack E; Gosse, Julie A; Nomikos, Athena P; Hamilton, Joshua W

    2006-12-01

    Chronic intake of arsenic (As) has been associated with increased risk of cancer, diabetes, developmental and reproductive problems, and cardiovascular disease. Recent studies suggest increased health risks with drinking water levels as low as 5-10 ppb. We previously reported that As disrupts glucocorticoid receptor (GR) mediated transcription in a very complex fashion. Low As levels (0.1-0.7 microM) stimulated transcription, whereas slightly higher levels (1-3 microM) were inhibitory. The DNA binding domain (DBD) was the minimal region of GR required for the response to As. Mutations in the DBD that alter the conformation of the dimerization domain (D-loop) to a DNA-bound GR conformation abolished the stimulatory effect and enhanced the inhibitory response to As. Here we report that receptors for progesterone (PR) and mineralocorticoids display a complex As response similar to that of the GR, suggesting a common mechanism for this effect. The complex response to As is not due to altered steroid or receptor levels. Moreover, a well-characterized GR dimerization mutant displayed a wild-type biphasic response to As for several divergent reporter genes, suggesting that dimerization is not critical for the response to As. Fluorescence polarization studies with purified PR and GR demonstrated that the specific PR/GR-DNA interaction is not altered in the presence of As. These results indicate that the numerous and diverse human health effects associated with As exposure may be mediated, at least in part, through its ability to simultaneously disrupt multiple hormone receptor systems. PMID:17173375

  14. The dose-response characteristics of the acute non-diuretic peripheral vascular effects of frusemide in normal subjects.

    OpenAIRE

    Johnston, G D; Nicholls, D P; Leahey, W J

    1984-01-01

    The peripheral venous and arterial effects of frusemide, plasma renin activity and plasma frusemide concentrations were examined during the 15 min period following the i.v. administration of 0, 5, 10, 20, 40 and 80 mg of frusemide in a group of nine salt depleted volunteers. The responses to 80 mg frusemide given orally during the 1 1 h period after administration were also examined. Increases in venous capacitance 5 min after administration of 5 and 10 mg frusemide were observed (P less than...

  15. Dose response effect of rutin a dietary antioxidant on alcohol-induced prooxidant and antioxidant imbalance - a histopathologic study.

    Science.gov (United States)

    Shenbagam, Madhavan; Nalini, Namasivayam

    2011-08-01

    The present study was designed to investigate the effect of rutin on ethanol-induced hepatotoxicity in a dose-dependent manner in rats. Male albino rats were divided into six groups. Group 1 rats served as control and group 2 rats received rutin 100 mg/kg body weight. Hepatotoxicity was induced in groups 3-6 rats (20% ethanol) for 60 days. In addition, groups 4-6 rats received rutin at doses of 25, 50, 100 mg/kg body weight, respectively for the last 30 days of the experiment. We observed a significant increase in the activities of liver marker enzymes, serum amino transferases, alkaline phosphatase, γ-glutamyl transpeptidase the levels of thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides, and a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione and its related enzymes, vitamins C and E when compared to ethanol-fed rats. Rutin supplementation along with ethanol significantly decreased the levels of liver marker enzymes, lipid peroxidation and significantly elevated the activities of liver SOD, CAT, GSH, glutathione peroxidase, vitamins C and E when compared to untreated ethanol supplemented rats. Among the three doses, 100 mg/kg body weight of rutin was found to exert a more pronounced hepatoprotective effect against ethanol-induced toxicity. Our results were also confirmed by the histopathologic observations. PMID:20727014

  16. Dose-Response on the Chemopreventive Effects of Sarcophine-Diol on UVB-Induced Skin Tumor Development in SKH-1 Hairless Mice

    Directory of Open Access Journals (Sweden)

    Chandradhar Dwivedi

    2012-09-01

    Full Text Available Sarcophine-diol (SD is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm2 UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm2. This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle, and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone 1 h before UVB radiation (30 mJ/cm2. The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

  17. Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat

    DEFF Research Database (Denmark)

    Breinholt, V.; Lauridsen, S. T.; Daneshvar, B.; Jakobsen, Jette

    2000-01-01

    The administration of lycopene to female rats at doses ranging from 0.001 to 0.1 g/kg b.w, per day for 2 weeks was found to alter the drug-metabolizing capacity and antioxidant status of the exposed animals. An investigation of four cytochrome P450-dependent enzymes revealed that benzyloxyresorufin...... O-dealkylase activity in the liver was significantly induced in a dose-dependent fashion at all lycopene doses investigated. Likewise, ethoxyresorufin O-dealkylase activity was induced, although only at the two highest lycopene concentrations tested. An investigation of selected phase 2...... detoxification enzymes provided evidence that lycopene was capable of inducing hepatic quinone reductase, approximately two-fold, at doses between 0.001 and 0.05 g/kg b.w, per day, whereas no effect was observed at the remaining doses tested. Glutathione transferase, using the two substrates, 2...

  18. Effect of thermal annealing on the thermoluminescent properties of nano-calcium fluoride and its dose-response characteristics.

    Science.gov (United States)

    Mundupuzhakal, J K; Biswas, R H; Chauhan, S; Varma, V; Acharya, Y B; Chakrabarty, B S

    2015-12-01

    Nano-CaF2, prepared by the co-precipitation method, was annealed under different annealing conditions to improve its thermoluminescence (TL) characteristics. Different annealing parameters, such as temperature (400-700°C), duration (1-4 h) and environment (vacuum and air), were explored. The effect on TL sensitivity, peak position (Tm) and full-width at half-maximum (FWHM) with respect to the different annealing conditions are discussed as they are the measure of crystallinity of the material. Annealing temperature of 500°C with annealing duration of two and a half hours in vacuum provided the highest luminescence response (i.e. maximum sensitivity, minimum peak temperature and FWHM). Wide detectable dose range (5 mGy to 2 kGy), absence of thermal quenching and sufficient activation energy (1.04 eV) of this phosphor make it suitable for dosimetric applications. PMID:25398396

  19. Antioxidant and Antidiabetic Effect of Hibiscus rosasinensis Flower Extract on Streptozotocin Induced Experimental Rats-a Dose Response Study

    Directory of Open Access Journals (Sweden)

    Mirunalini SANKARAN

    2011-11-01

    Full Text Available The present study was designed to evaluate the antidiabetic and antioxidant effect of Hibiscus rosasinensis against streptozotocin induced diabetic rats. Streptozotocin (STZ was administered as a single dose (40 mg/kg to induce diabetes. The hypoglycemic activity of Hibiscus rosasinensis extract (HRSEt was investigated in a dose dependent manner such as (125, 250 and 500 mg/kg bwt by evaluating various biochemical parameters. The levels of blood glucose, carbohydrate metabolizing enzymes, TBARS, enzymatic and non-enzymatic antioxidants and lipid profiles were found to be significantly increased in diabetic rats when compared to control groups. Administration of extract in the treated groups showed altered changes in the above mentioned parameters and found that among the three doseses, 250 mg/kg showed best result when compared to other two doses. HRSEt possess antioxidant, hypoglycemic and hypolipidemic activity against streptozotocin induced diabetic rats. However the detailed mechanism(s of action will require elucidating in further studies.

  20. Effect of thermal annealing on the thermoluminescent properties of nano-calcium fluoride and its dose-response characteristics

    International Nuclear Information System (INIS)

    Nano-CaF2, prepared by the co-precipitation method, was annealed under different annealing conditions to improve its thermoluminescence (TL) characteristics. Different annealing parameters, such as temperature (400-700 deg. C), duration (1-4 h) and environment (vacuum and air), were explored. The effect on TL sensitivity, peak position (Tm) and full-width at half-maximum (FWHM) with respect to the different annealing conditions are discussed as they are the measure of crystallinity of the material. Annealing temperature of 500 deg. C with annealing duration of two and a half hours in vacuum provided the highest luminescence response (i.e. maximum sensitivity, minimum peak temperature and FWHM). Wide detectable dose range (5 mGy to 2 kGy), absence of thermal quenching and sufficient activation energy (1.04 eV) of this phosphor make it suitable for dosimetric applications. (authors)

  1. Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat

    DEFF Research Database (Denmark)

    Breinholt, V.; Lauridsen, S. T.; Daneshvar, B.;

    2000-01-01

    -metabolizing enzymes involved in the protection against oxidative stress and cancer. The fact that these enzymatic activities are induced at all of these very low plasma levels, could be taken to suggest that modulation of antioxidant and drug-metabolizing enzymes map indeed be relevant to humans, which in general......The administration of lycopene to female rats at doses ranging from 0.001 to 0.1 g/kg b.w, per day for 2 weeks was found to alter the drug-metabolizing capacity and antioxidant status of the exposed animals. An investigation of four cytochrome P450-dependent enzymes revealed that benzyloxyresorufin...... detoxification enzymes provided evidence that lycopene was capable of inducing hepatic quinone reductase, approximately two-fold, at doses between 0.001 and 0.05 g/kg b.w, per day, whereas no effect was observed at the remaining doses tested. Glutathione transferase, using the two substrates, 2...

  2. Dose-Response Analysis of the Effect of Carbidopa-Levodopa Extended-Release Capsules (IPX066) in Levodopa-Naive Patients With Parkinson Disease.

    Science.gov (United States)

    Mao, Zhongping Lily; Modi, Nishit B

    2016-08-01

    Parkinson disease is an age-related disorder of the central nervous system principally due to loss of dopamine-producing cells in the midbrain. Levodopa, in combination with carbidopa, is widely regarded as an effective treatment for the symptoms of Parkinson disease. A dose-response relationship is established for carbidopa-levodopa extended-release capsules (IPX066) in levodopa-naive Parkinson disease patients using a disease progression model. Unified Parkinson Disease Rating Scale (UPDRS) part II plus part III scores from 171 North American patients treated with placebo or IPX066 for approximately 30 weeks from a double-blind, parallel-group, dose-ranging study were used to develop the pharmacodynamic model. The model comprised 3 components: a linear function describing disease progression, a component describing placebo (or nonlevodopa) effects, and a component to describe the effect of levodopa. Natural disease progression in early Parkinson disease as measured by UPDRS was 11.6 units/year and faster in patients with more severe disease (Hoehn-Yahr stage 3). Maximum placebo/nonlevodopa response was 23.0% of baseline UPDRS. Maximum levodopa effect from IPX066 was 76.7% of baseline UPDRS, and the ED50 was 450 mg levodopa. Equilibration half-life for the effect compartment was 62.8 days. Increasing age increased and being female decreased equilibration half-life. The quantitative model allowed description of the entire time course of response to clinical trial intervention. PMID:26632091

  3. "THE STUDY OF DOSE-RESPONSE MITOGENIC EFFECT OF L-DOPA ON THE HUMAN PERIODONTAL LIGAMENT FIBROBLAST CELLS"

    Directory of Open Access Journals (Sweden)

    M. Zarabian

    2004-10-01

    Full Text Available Avulsion is one of the most serious emergencies in dental office. In the event of any problem, the tooth should be stored in a medium that supports the periodontal ligament cell viability. In other clinical situations, preserving media, growth factors and mitogenic products may be useful in repairing the traumatized tissues. It has been previously reported that levodopa (L-dopa accelerates healing by increasing the growth hormone level. In this study, the local effect of L-dopa, as a mitogen, on human periodontal ligament fibroblast (HPLF cells was evaluated. Samples from impacted or semiimpacted wisdom or canine teeth, which were devoid of inflammation, were taken. The cells obtained from this tissue were cultured in an appropriate medium. The passage numbers between 3-6 were taken for further experiments. The viability of HPLF cells, which were treated by L-dopa, was evaluated by trypan blue dye exclusion and neutral red assay. Results indicated that low concentration of L-dopa produces significant increase of these cells compared to control group. These results confirmed previous studies about direct action of L- dopa on the viability of HPLF cells. On the basis of this study and previous reports, presence of L-dopa in preserving media may be useful in increasing the self-life transferring HPLF cells.

  4. Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours

    International Nuclear Information System (INIS)

    Peptide receptor radionuclide therapy using β-emitting radiolabelled somatostatin analogues like DOTA,Tyr3-octreotate shows beneficial results in patients suffering from somatostatin receptor overexpressing tumours. However, after high-dose therapy partial renal reabsorption of radiopeptides may lead to nephrotoxicity. Co-infusion of lysine/arginine lowers renal retention of these radiopeptides without affecting tumour uptake. Recently co-administration of Gelofusine has been described to have a comparable kidney-protecting effect in rats. In the present study optimal dosing of Gelofusine co-administration was studied in tumour-bearing rats. Doses of 40, 80, 120 or 160 mg/kg Gelofusine were co-injected with 15 μg DOTA,Tyr3-octreotate, labelled with 3 MBq 111In for biodistribution (24 h post-injection, n = 4 per group) and with 60 MBq 111In for microSPECT imaging experiments at 3, 24 and 48 h post-injection. An additional group of rats received 80 mg/kg Gelofusine plus 400 mg/kg lysine co-injection. Biodistribution studies were performed both in older (475 g) and younger (300 g) rats, the latter bearing CA20948 tumours. Co-injection of 40 mg/kg Gelofusine resulted in 40-50% reduction of renal uptake and retention of 111In-DOTA,Tyr3-octreotate, whereas higher doses further increased the reduction to 50-60% in both groups of rats. Combining Gelofusine and lysine caused 70% reduction of renal uptake. The uptake of radiolabelled octreotate both in somatostatin receptor-expressing normal tissues and tumours was not affected by Gelofusine co-injection. In rats co-injection of 80 mg/kg Gelofusine resulted in maximum reduction of renal retention of 111In-DOTA,Tyr3-octreotate, which was further improved when combined with lysine. Tumour uptake of radiolabelled octreotate was not affected, resulting in an increased tumour to kidney ratio. (orig.)

  5. 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)

    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

  6. Statistical and low dose response

    International Nuclear Information System (INIS)

    The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem

  7. Biological effectiveness of fission neutrons

    International Nuclear Information System (INIS)

    Human peripheral blood lymphocytes were exposed to the uranium fission neutrons with different energy spectra, and the effects of changing pattern of energy spectrum on the relative biological effectiveness (RBE) were studied by analyzing dose-response relationship of chromosome aberrations. When the contribution of contaminated gamma-rays was subtracted, the efficiency of chromosomal response to the neutron dose was found to be refractory to the difference in the energy spectrum while the mean energy ranged from 2 MeV to 27 keV. This chromosomal refractoriness to energy spectrum may be explained by the similarity of energy spectrum for kerma contribution; most of the doses being given by neutrons with energy above 50 keV. Small doses given by short tracks may be less efficient. A comparison of these observations with chromosome aberration frequencies in lymphocytes of A-bomb survivors leads to somewhat higher estimate of neutron dose in Hiroshima than the estimate by the recently revised dosimetry system, DS86. (author)

  8. A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects.

    Directory of Open Access Journals (Sweden)

    Luciana Cadore Stefani

    Full Text Available Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation.The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects.Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT and the pressure pain tolerance (PPTo. Quantitative sensory testing (QST was used to measure the heat pain threshold (HPT and the heat pain tolerance (HPTo. Sedation was assessed with a visual analogue scale and bispectral analysis.Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg and the highest (0.25 mg/kg melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R(2  = 0.492 for HPT, R(2  = 0.538 for PPT, R(2  = 0.558 for HPTo and R(2  = 0.584 for PPTo.The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec: (U1111

  9. Dose-response in stereotactic irradiation of lung tumors

    International Nuclear Information System (INIS)

    The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors (36 NSCLC and 56 metastases) was evaluated. Short course irradiation of 1-8 fractions with different fraction doses was used. After a median follow-up of 14 months (2-85 months) 11 local recurrences were observed with significant advantage for higher doses. When normalization to a biologically effective dose (BED) is used a dose of 94 Gy at the isocenter and 50 Gy at the PTV-margin are demonstrated to give 50% probability of tumor control (TCD50). Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control

  10. Proposal of a probabilistic dose-response model

    International Nuclear Information System (INIS)

    A biologically updated dose-response model is presented as an alternative to the linear-quadratic model currently in use for cancer risk assessment. The new model is based on the probability functions for misrepair and/or unrepair of DNA lesions, in terms of the radiation damage production rate in the cell (supposedly, a stem cell) and its repair-rate constant. The model makes use, interpreting it on the basis of misrepair probabilities, of the ''dose and dose-rate effectiveness factor'' of ICRP, and provides the way for a continuous extrapolation between the high and low dose-rate regions, ratifying the ''linear non-threshold hypothesis'' as the main option. Anyhow, the model throws some doubts about the additive property of the dose. (author)

  11. Effect of ethiopia's health extension program on maternal and newborn health care practices in 101 rural districts: a dose-response study.

    Directory of Open Access Journals (Sweden)

    Ali Mehryar Karim

    Full Text Available BACKGROUND: Improving newborn survival is essential if Ethiopia is to achieve Millennium Development Goal 4. The national Health Extension Program (HEP includes community-based newborn survival interventions. We report the effect of these interventions on changes in maternal and newborn health care practices between 2008 and 2010 in 101 districts, comprising 11.6 million people, or 16% of Ethiopia's population. METHODS AND FINDINGS: Using data from cross-sectional surveys in December 2008 and December 2010 from a representative sample of 117 communities (kebeles, we estimated the prevalence of maternal and newborn care practices, and a program intensity score in each community. Women with children aged 0 to 11 months reported care practices for their most recent pregnancy and childbirth. The program intensity score ranged between zero and ten and was derived from four outreach activities of the HEP front-line health workers. Dose-response relationships between changes in program intensity and the changes in maternal and newborn health were investigated using regression methods, controlling for secular trend, respondents' background characteristics, and community-level factors. Between 2008 and 2010, median program intensity score increased 2.4-fold. For every unit increase in the score, the odds of receiving antenatal care increased by 1.13 times (95% CI 1.03-1.23; the odds of birth preparedness increased by 1.31 times (1.19-1.44; the odds of receiving postnatal care increased by 1.60 times (1.34-1.91; and the odds of initiating breastfeeding immediately after birth increased by 1.10 times (1.02-1.20. Program intensity score was not associated with skilled deliveries, nor with some of the other newborn health care indicators. CONCLUSIONS: The results of our analysis suggest that Ethiopia's HEP platform has improved maternal and newborn health care practices at scale. However, implementation research will be required to address the maternal and

  12. 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 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...

  13. Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study.

    Science.gov (United States)

    Pasquali, Renato; Ambrosi, Bruno; Armanini, Decio; Cavagnini, Francesco; Uberti, Ettore Degli; Del Rio, Graziano; de Pergola, Giovanni; Maccario, Mauro; Mantero, Franco; Marugo, Mario; Rotella, Carlo Maria; Vettor, Roberto

    2002-01-01

    There is increasing evidence that the abdominal obesity phenotype may be associated with multiple alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in both sexes. Our hypothesis is that the lack of adequate cortisol suppression after the dexamethasone test may constitute an indirect marker of HPA axis hyperactivity in the presence of the abdominal obesity phenotype. A total of 34 normal-weight (13 men and 21 women) and 87 obese (36 men and 51 women), healthy, nondepressed subjects therefore underwent four different dexamethasone suppression tests randomly performed at varying intervals of at least 1 wk between each test. After a standard overnight 1-mg dexamethasone test, which served as a reference, three other tests were randomly performed at 1-wk intervals by administering 0.0035, 0.0070, and 0.015 mg oral dexamethasone per kilogram of body weight overnight. Blood samples were obtained for cortisol, ACTH, and dexamethasone. Results were analyzed separately in men and women as well as in normal-weight [body mass index (BMI) 25 kg/m(2)) subjects. The waist circumference and the waist to hip ratio (WHR) were used as markers of body fat distribution. After the standard 1-mg test, cortisol suppression was greater than 90% in all subjects. However, after each test, obese women had significantly higher values of percent cortisol and percent ACTH suppression than normal-weight women without any difference between obese and normal-weight men. Considering the response to the three variable-dose tests, a clear dose- response pattern (P < 0.001 for trend analysis) in percent cortisol and percent ACTH suppression was found in all subjects. After each test men had significantly higher dexamethasone levels than women, regardless of BMI. However, obese women, but not men, had significantly higher dexamethasone levels after each test than their normal-weight counterpart. Plasma dexamethasone concentrations were dose related (P < 0.001 for trend

  14. Biological Effects after Prenatal Irradiation

    International Nuclear Information System (INIS)

    A Task Group of the International Commission on Radiological Protection (ICRP) has finished a report Biological Effects after Prenatal Irradiation (Embryo and Fetus) which has been approved by the Main Commission and Will be Published. Some new important scientific data shall be discussed in this contribution. During the preimplantation period lethality of the mammalian embryo is the dominating radiation effect. However, in mouse strains with genetic predispositions it has been shown that also malformations can be caused. This effect is genetically determined and its mechanisms is different from the induction of malformations during major organogenesis. Radiation exposures during this prenatal period leads ato an increase of genomic instability of cells in the normal appearing fetuses. These radiation effects can be transmitted to the next generation. A renewed analysis of individuals with severe mental retardation after exposures during the 8th to 15th week post conception in Hiroshima and Nagasaki gives evidence that a threshold dose exists for this effect around 300 mGy. This is supported by a number of experimental animal data which have been obtained from cellular and molecular investigations during the brain development. The data show the high radiosensitivity of the developing brain but also the various compensatory mechanisms and the enormous plasticity of these processes. The radiosensitivity varies strongly during the prenatal development. The highest sensitivity is found during the early and mid fetal period which is coinciding with weeks 8-15 post conception in humans. The lowest doses causing persistent damage are in the range of 100 to 300 mGy. For intelligence quotient scores a linear dose response model provides a satisfactory fit. From the experimental data it can be concluded that the fetal stage is most sensitive to the carcinogenic effect in comparison to the other prenatal stages. Such as clear situation cannot be obtained from the

  15. Dose-response analysis using R

    DEFF Research Database (Denmark)

    Ritz, Christian; Baty, Florent; Streibig, Jens Carl;

    2015-01-01

    Dose-response analysis can be carried out using multi-purpose commercial statistical software, but except for a few special cases the analysis easily becomes cumbersome as relevant, non-standard output requires manual programming. The extension package drc for the statistical environment R provides...... a flexible and versatile infrastructure for dose-response analyses in general. The present version of the package, reflecting extensions and modifications over the last decade, provides a user-friendly interface to specify the model assumptions about the dose-response relationship and comes with a...

  16. Dose-response aligned circuits in signaling systems.

    Directory of Open Access Journals (Sweden)

    Long Yan

    Full Text Available Cells use biological signal transduction pathways to respond to environmental stimuli and the behavior of many cell types depends on precise sensing and transmission of external information. A notable property of signal transduction that was characterized in the Saccharomyces cerevisiae yeast cell and many mammalian cells is the alignment of dose-response curves. It was found that the dose response of the receptor matches closely the dose responses of the downstream. This dose-response alignment (DoRA renders equal sensitivities and concordant responses in different parts of signaling system and guarantees a faithful information transmission. The experimental observations raise interesting questions about the nature of the information transmission through DoRA signaling networks and design principles of signaling systems with this function. Here, we performed an exhaustive computational analysis on network architectures that underlie the DoRA function in simple regulatory networks composed of two and three enzymes. The minimal circuits capable of DoRA were examined with Michaelis-Menten kinetics. Several motifs that are essential for the dynamical function of DoRA were identified. Systematic analysis of the topology space of robust DoRA circuits revealed that, rather than fine-tuning the network's parameters, the function is primarily realized by enzymatic regulations on the controlled node that are constrained in limiting regions of saturation or linearity.

  17. Dose/response relationships and policy formulation

    International Nuclear Information System (INIS)

    The ICRP 26 cost/benefit approach to establishing operational radiation protection guidelines is discussed. The purpose is to aid the policy maker in the decision making process, using as a basis the dose-response curve

  18. Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

    Science.gov (United States)

    Seong, Ki Moon; Seo, Songwon; Lee, Dalnim; Kim, Min-Jeong; Lee, Seung-Sook; Park, Sunhoo; Jin, Young Woo

    2016-02-01

    Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation. PMID:26908982

  19. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu

    2005-12-15

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.

  20. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    International Nuclear Information System (INIS)

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology

  1. Effect of iron salt counter ion in dose-response curves for inactivation of Fusarium solani in water through solar driven Fenton-like processes

    Science.gov (United States)

    Aurioles-López, Verónica; Polo-López, M. Inmaculada; Fernández-Ibáñez, Pilar; López-Malo, Aurelio; Bandala, Erick R.

    2016-02-01

    The inactivation of Fusarium solani in water was assessed by solar driven Fenton-like processes using three different iron salts: ferric acetylacetonate (Fe(acac)3), ferric chloride (FeCl3) and ferrous sulfate (FeSO4). The experimental conditions tested were [Fe] ≈ 5 mg L-1, [H2O2] ≈ 10 mg L-1 and [Fe] ≈ 10 mg L-1; [H2O2] ≈ 20 mg L-1 mild and high, respectively, and pH 3.0 and 5.0, under solar radiation. The highest inactivation rates were observed at high reaction conditions for the three iron salts tested at pH 5.0 with less than 3.0 kJ L-1 of accumulate energy (QUV) to achieve over 99.9% of F. solani inactivation. Fe(acac)3 was the best iron salt to accomplishing F. solani inactivation. The modified Fermi equation was used to fix the experimental inactivation, data showed it was helpful for modeling the process, adequately describing dose-response curves. Inactivation process using FeSO4 at pH 3.0 was modeled fairly with r2 = 0.98 and 0.99 (mild and high concentration, respectively). Fe(acac)3, FeCl3 and FeSO4 at high concentration (i.e. [Fe] ≈ 10 mg L-1; [H2O2] ≈ 20 mg L-1) and pH 5.0 showed the highest fitting values (r2 = 0.99). Iron salt type showed a remarkable influence on the Fenton-like inactivation process.

  2. Dose-response relationship with radiotherapy: an evidence?

    International Nuclear Information System (INIS)

    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)

  3. Relative biological effectiveness (RBE) of fission neutrons and gamma rays at occupational exposure levels

    International Nuclear Information System (INIS)

    The pathologic consequences of exposure to 60 equal once-weekly doses of fission neutron or 60Co gamma rays have been subjected to dose-response analyses for the purposes of generating relative biological effectiveness (RBE) values for the major causes of death of for tumor occurrences. Cumulative probabilities of death or occurrence were generated for 15 categories of neoplastic disease for the time interval of 800--999 days since first exposure. These probabilities were developed for each dose, sex, and radiation quality, and a dose-response analysis was applied to derive linear risk coefficients of death or occurrence. 40 refs., 16 figs., 9 tabs

  4. Biological Effects of Ionizing Radiation

    Science.gov (United States)

    Ingram, M.; Mason, W. B.; Whipple, G. H.; Howland, J. W.

    1952-04-07

    This report presents a review of present knowledge and concepts of the biological effects of ionizing radiations. Among the topics discussed are the physical and chemical effects of ionizing radiation on biological systems, morphological and physiological changes observed in biological systems subjected to ionizing radiations, physiological changes in the intact animal, latent changes following exposure of biological systems to ionizing radiations, factors influencing the biological response to ionizing radiation, relative effects of various ionizing radiations, and biological dosimetry.

  5. Nonlinearity of dose responses in thermoluminescence dosimetry

    International Nuclear Information System (INIS)

    All of dose responses in thermoluminescence (TL) dosimetry can be described by a dose response function derived from statistical Poisson distribution. Two characteristic parameters in this function, one hit factor R and characteristic dose D0, can be used to analyze the nonlinearity of TL responses. The one hit factor R indicates whether there is a linear region in the dose responses, and that the responses are linear-sublinear or linear-supralinear-sublinear. The characteristic dose D0 is used to compare the range of linear region in responses and sensitivity of TLD. When coupling with physical mechanisms in the TL process, the dominant features of the TL nonlinear behavior observed in experiments can be explained. (8 refs., 7 figs., 1 tab.)

  6. Characterization of a developmental toxicity dose-response model

    Energy Technology Data Exchange (ETDEWEB)

    Faustman, E.M.; Wellington, D.G.; Smith, W.P.; Kimmel, C.A.

    1989-02-01

    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose.

  7. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

    Science.gov (United States)

    Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

    2003-01-01

    OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness

  8. Quantum Effects in Biology

    Science.gov (United States)

    Mohseni, Masoud; Omar, Yasser; Engel, Gregory S.; Plenio, Martin B.

    2014-08-01

    List of contributors; Preface; Part I. Introduction: 1. Quantum biology: introduction Graham R. Fleming and Gregory D. Scholes; 2. Open quantum system approaches to biological systems Alireza Shabani, Masoud Mohseni, Seogjoo Jang, Akihito Ishizaki, Martin Plenio, Patrick Rebentrost, Alàn Aspuru-Guzik, Jianshu Cao, Seth Lloyd and Robert Silbey; 3. Generalized Förster resonance energy transfer Seogjoo Jang, Hoda Hossein-Nejad and Gregory D. Scholes; 4. Multidimensional electronic spectroscopy Tomáš Mančal; Part II. Quantum Effects in Bacterial Photosynthetic Energy Transfer: 5. Structure, function, and quantum dynamics of pigment protein complexes Ioan Kosztin and Klaus Schulten; 6. Direct observation of quantum coherence Gregory S. Engel; 7. Environment-assisted quantum transport Masoud Mohseni, Alàn Aspuru-Guzik, Patrick Rebentrost, Alireza Shabani, Seth Lloyd, Susana F. Huelga and Martin B. Plenio; Part III. Quantum Effects in Higher Organisms and Applications: 8. Excitation energy transfer in higher plants Elisabet Romero, Vladimir I. Novoderezhkin and Rienk van Grondelle; 9. Electron transfer in proteins Spiros S. Skourtis; 10. A chemical compass for bird navigation Ilia A. Solov'yov, Thorsten Ritz, Klaus Schulten and Peter J. Hore; 11. Quantum biology of retinal Klaus Schulten and Shigehiko Hayashi; 12. Quantum vibrational effects on sense of smell A. M. Stoneham, L. Turin, J. C. Brookes and A. P. Horsfield; 13. A perspective on possible manifestations of entanglement in biological systems Hans J. Briegel and Sandu Popescu; 14. Design and applications of bio-inspired quantum materials Mohan Sarovar, Dörthe M. Eisele and K. Birgitta Whaley; 15. Coherent excitons in carbon nanotubes Leonas Valkunas and Darius Abramavicius; Glossary; References; Index.

  9. Biological radiation effects

    International Nuclear Information System (INIS)

    The book covers all aspects of biological radiation effects and provides the fundamental basis for understanding the necessity of radiation protection as well as applications in radiotherapy. The physical basis is dealt with in some detail, and the effects at the subcellular and the cellular level are thoroughly discussed, taking into account modern developments and techniques. The effects on the human organism are reviewed, both from the point of view of applications in medicine as well as with regard to radiation hazards (teratogenic, gonadal and carcinogenic effects). It can be used by graduate students as an introduction and as a source book for all who want to become acquainted with this important field. It is an extended version of the original German book containing updated information and new material. (orig.) With 273 figs

  10. Biological effects of neutrons

    International Nuclear Information System (INIS)

    Although the occasion to be exposed to neutrons is rare in our life, except for nuclear accidents like in the critical accident at Tokai-mura in 1999, countermeasures against accident should be always prepared. In the Tokai-mura accident, residents received less than 21 mSv of neutrons and gamma rays. The cancer risks and fetal effects of low doses of neutrons were matters of concern among residents. The purpose of this program is to investigate the relative biological effectiveness (RBE) for leukemias, and thereby to assess risks of neutrons. Animal experiments are planed to obtain the following RBEs: (1) RBE for the induction of leukemias in mice and (2) RBE for effects on fetuses. Cyclotron fast neutrons (10 MeV) and electrostatic accelerator-derived neutrons (2 MeV) are used for exposure in this program. Furthermore, cytological and cytogenetic analyses will be performed. (author)

  11. Modeling of dose-response relationships.

    OpenAIRE

    Altshuler, B

    1981-01-01

    The main dose-response models for chronic toxicity are considered. For dichotomous response, the log probit, multi-hit, and multistage models are presented. For time-to-occurrence response, the log-normal and three variations of multistage models are presented. Finally, the Cornfield hockey-stick model is considered, and, for low-dose extrapolation, it is suggested that response be taken to be proportional to dose and to a power of time determined by background response.

  12. Inhalation Anthrax: Dose Response and Risk Analysis

    OpenAIRE

    Coleman, Margaret E.; Thran, Brandolyn; Morse, Stephen S.; Hugh-Jones, Martin; Massulik, Stacey

    2008-01-01

    The notion that inhalation of a single Bacillus anthracis spore is fatal has become entrenched nearly to the point of urban legend, in part because of incomplete articulation of the scientific basis for microbial risk assessment, particularly dose-response assessment. Risk analysis (ie, risk assessment, risk communication, risk management) necessitates transparency: distinguishing scientific facts, hypotheses, judgments, biases in interpretations, and potential misinformation. The difficulty ...

  13. A Human Vascular Model Based on Microdialysis for the Assessment of the Vasoconstrictive Dose-Response Effects of Norepinephrine and Vasopressin in Skin

    OpenAIRE

    Tchou Folkesson, Kim; Samuelsson, Anders; Tesselaar, Erik; Dahlström, Bengt; Sjöberg, Folke

    2012-01-01

    Abstract Objective: Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin. Methods: We investigated whether increasing concentrations of norepinephrine (NE, 1.859 mu mol/L) and vasopressin (VP, 1100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent cha...

  14. Hypokalaemia and other non-bronchial effects of inhaled fenoterol and salbutamol: a placebo-controlled dose-response study in healthy volunteers.

    OpenAIRE

    Scheinin, M; Koulu, M.; Laurikainen, E.; Allonen, H

    1987-01-01

    1. The hypokalaemia-inducing effects of two widely used inhaled antiasthmatic beta 2-adrenoceptor agonists, fenoterol and salbutamol, were compared in six healthy male volunteers. 2. Each drug was administered in three different doses, 400, 600 and 800 micrograms, which were repeated three times with 30 min intervals (total doses 1200, 1800 and 2400 micrograms in 1 h). The treatments were given at 1 week intervals in random order in a single-blind fashion. 3. The concentration of potassium in...

  15. Effect of hydroalcoholic fruit extract of Persea americana Mill. on high fat diet induced obesity: A dose response study in rats.

    Science.gov (United States)

    Monika, Padmanabhan; Geetha, Arumugam

    2016-06-01

    The fruits of Persea Americana Mill., commonly known as Avocado, are traditionally consumed for various health benefits including weight reduction. Here, we studied the effect of hydroalcoholic fruit extract of Persea americana (HAEPA) on high fat diet (HFD) induced obesity in rats. Obesity was induced in male Sprague Dawley rats by feeding HFD for 14 wk. The hypolipidemic effect was evaluated by co-administering 25, 50, 100 and 200 mg/kg body wt. of HAEPA. There was a significant increase in weight gain, body mass index (BMI), blood lipids, low density lipoproteins (LDL), lipid peroxides (LPO) and serum transaminases in HFD fed rats. HFD+HAEPA fed rats showed a significant decrease in blood lipids, LPO, liver lipids and increase in antioxidant status when compared to HFD control rats. The activity of lipid metabolic key enzymes such as fatty acid synthase and HMG CoA reductase in liver were also found to be decreased significantly in HAEPA co-administered rats. Lipoprotein lipase activity was found increased in HFD+HAEPA rats. Among the 4 doses studied, 100 mg of HAEPA/kg body wt. exhibited optimum hypolipidemic activity. Histopathological observations in liver and visceral adipose tissue added more evidence for the lipid lowering effect of HAEPA. It can be concluded that avocado fruit extract can act as hypolipidemic agent probably by modulating the activities of HMG CoA reductase and fatty acid synthase in liver. PMID:27468463

  16. Dose-response inhibitory effects of purified cathinone from khat (Catha edulis) on cortisol and prolactin release in vervet monkeys (Chlorocebus aethiops).

    Science.gov (United States)

    Nyongesa, Albert W; Oduma, Jemimah A; Nakajima, Motohiro; Odongo, Hesbon O; Adoyo, Pius A; al'Absi, Mustafa

    2014-06-01

    This study reports acute and sub-chronic effects of cathinone on hormonal alterations in single-caged vervet monkeys. Fourteen adult vervet monkeys were used, 12 of which were treated and 2 controls. Pre-treatment phase of 1 month aimed at establishing baseline levels of hormones while treatment phase of 4 months considered the dose- and time-response effects of cathinone on serum cortisol and prolactin levels. Test animals were allocated four groups of three animals each and administered 0.8, 1.6, 3.2 and 6.4 mg/kg body weight of cathinone orally while controls were administered normal saline. Treatment was done at alternate days of each week. Serum prolactin and cortisol immunoassays were done. Hormonal data was analysed by repeated measures ANCOVA. Results indicate a dose [F (4, 8) = 218, P < 0.001] and time [F (18, 142) = 21.7, P < 0.001] dependent effect of cathinone on cortisol levels with a significant dose by week interaction [F (71, 142) = 4.86, P < 0.001]. Similarly, there was a decrease in serum prolactin [F (4, 8) = 267, P < 0.001] with escalating doses of cathinone with a significant dose x week interaction [F (59, 118) = 13.03, P < 0.001]. The findings demonstrate that at high doses and long-term exposure, cathinone causes hormonal alterations probably via changes in hypothalamo-hypophyseo-adrenocortical and gonadal axes integrity. PMID:24190428

  17. Evaluating in vitro dose-response effects of Lavandula officinalis essential oil on rumen fermentation characteristics, methane production and ruminal acidosis

    OpenAIRE

    Yadeghari, Shahin; Malecky, Mostafa; Dehghan Banadaky, Mehdi; Navidshad, Bahman

    2015-01-01

    Four in vitro experiments (Exp.) were conducted to evaluate lavender essential oil (LEO) effects at 0 (control), 250 (low dose), 500 (medium dose), 750 and 1000 µL per L (high doses) of incubation medium on rumen gas production kinetics (Exp.1), ruminal digestibility and fermentation (Exp.2), methane production (Exp.3) and rumen acidosis (Exp.4). The asymptote of gas production (A) increased quadratically (p < 0.001), but the lag phase (L) increased (p = 0.003), and gas production rate (µ) de...

  18. Dose-response effects of estrogenic mycotoxins (zearalenone, alpha- and beta-zearalenol on motility, hyperactivation and the acrosome reaction of stallion sperm

    Directory of Open Access Journals (Sweden)

    Colenbrander Ben

    2011-10-01

    Full Text Available Abstract Background The aim of this study was to investigate the in vitro effects of the Fusarium fungus-derived mycotoxin, zearalenone and its derivatives alpha-zearalenol and beta-zearalenol on motility parameters and the acrosome reaction of stallion sperm. Since the toxic effects of zearalenone and its derivatives are thought to result from their structural similarity to 17beta-estradiol, 17beta-estradiol was used as a positive control for 'estrogen-like' effects. Methods Stallion spermatozoa were exposed in vitro to zearalenone, alpha-zearalenol, beta-zearalenol or 17beta-estradiol at concentrations ranging from 1 pM - 0.1 mM. After 2 hours exposure, motility parameters were evaluated by computer-assisted analysis, and acrosome integrity was examined by flow cytometry after staining with fluoroscein-conjugated peanut agglutinin. Results Mycotoxins affected sperm parameters only at the highest concentration tested (0.1 mM after 2 hours exposure. In this respect, all of the compounds reduced the average path velocity, but only alpha-zearalenol reduced percentages of motile and progressively motile sperm. Induction of motility patterns consistent with hyperactivation was stimulated according to the following rank of potency: alpha-zearalenol >17beta-estradiol > zearalenone = beta-zearalenol. The hyperactivity-associated changes observed included reductions in straight-line velocity and linearity of movement, and an increase in the amplitude of lateral head displacement, while curvilinear velocity was unchanged. In addition, whereas alpha- and beta- zearalenol increased the percentages of live acrosome-reacted sperm, zearalenone and 17beta-estradiol had no apparent effect on acrosome status. In short, alpha-zearalenol inhibited normal sperm motility, but stimulated hyperactive motility in the remaining motile cells and simultaneously induced the acrosome reaction. Beta-zearalenol induced the acrosome reaction without altering motility

  19. An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males

    Directory of Open Access Journals (Sweden)

    Anderson Mark L

    2008-08-01

    Full Text Available Abstract Background Maintaining endogenous testosterone (T levels as men age may slow the symptoms of sarcopenia, andropause and decline in physical performance. Drugs inhibiting the enzyme 5α-reductase (5AR produce increased blood levels of T and decreased levels of dihydrotestosterone (DHT. However, symptoms of gynecomastia have been reported due to the aromatase (AER enzyme converting excess T to estradiol (ES. The carotenoid astaxanthin (AX from Haematococcus pluvialis, Saw Palmetto berry lipid extract (SPLE from Serenoa repens and the precise combination of these dietary supplements, Alphastat® (Mytosterone(™, have been reported to have inhibitory effects on both 5AR and AER in-vitro. Concomitant regulation of both enzymes in-vivo would cause DHT and ES blood levels to decrease and T levels to increase. The purpose of this clinical study was to determine if patented Alphastat® (Mytosterone(™ could produce these effects in a dose dependent manner. Methods To investigate this clinically, 42 healthy males ages 37 to 70 years were divided into two groups of twenty-one and dosed with either 800 mg/day or 2000 mg/day of Alphastat® (Mytosterone(™ for fourteen days. Blood samples were collected on days 0, 3, 7 and 14 and assayed for T, DHT and ES. Body weight and blood pressure data were collected prior to blood collection. One-way, repeated measures analysis of variance (ANOVA-RM was performed at a significance level of alpha = 0.05 to determine differences from baseline within each group. Two-way analysis of variance (ANOVA-2 was performed after baseline subtraction, at a significance level of alpha = 0.05 to determine differences between dose groups. Results are expressed as means ± SEM. Results ANOVA-RM showed significant within group increases in serum total T and significant decreases in serum DHT from baseline in both dose groups at a significance level of alpha = 0.05. Significant decreases in serum ES are reported for the 2000

  20. The dose-response effect of acute intravenous transplantation of human umbilical cord blood cells on brain damage and spatial memory deficits in neonatal hypoxia-ischemia.

    Science.gov (United States)

    de Paula, S; Greggio, S; Marinowic, D R; Machado, D C; DaCosta, J Costa

    2012-05-17

    Despite the beneficial effects of cell-based therapies on brain repair shown in most studies, there has not been a consensus regarding the optimal dose of human umbilical cord blood cells (HUCBC) for neonatal hypoxia-ischemia (HI). In this study, we compared the long-term effects of intravenous administration of HUCBC at three different doses on spatial memory and brain morphological changes after HI in newborn Wistar rats. In addition, we tested whether the transplanted HUCBC migrate to the injured brain after transplantation. Seven-day-old animals underwent right carotid artery occlusion and were exposed to 8% O(2) inhalation for 2 h. After 24 h, randomly selected animals were assigned to four different experimental groups: HI rats administered with vehicle (HI+vehicle), HI rats treated with 1×10(6) (HI+low-dose), 1×10(7) (HI+medium-dose), and 1×10(8) (HI+high-dose) HUCBC into the jugular vein. A control group (sham-operated) was also included in this study. After 8 weeks of transplantation, spatial memory performance was assessed using the Morris water maze (MWM), and subsequently, the animals were euthanized for brain morphological analysis using stereological methods. In addition, we performed immunofluorescence and polymerase chain reaction (PCR) analyses to identify HUCBC in the rat brain 7 days after transplantation. The MWM test showed a significant spatial memory recovery at the highest HUCBC dose compared with HI+vehicle rats (Pbrain atrophy was also significantly lower in the HI+medium- and high-dose groups compared with the HI+vehicle animals (Pbrains by immunohistochemistry and PCR analyses 7 days after intravenous administration. These results revealed that HUCBC transplantation has the dose-dependent potential to promote robust tissue repair and stable cognitive improvement after HI brain injury. PMID:22441035

  1. Biological radiation effects

    International Nuclear Information System (INIS)

    This work examines ionizing radiations: what they are, where they come from, their actions and consequences, finally the norms and preventive measures necessary to avoid serious contamination, whether the individual or the population in general is involved. Man has always been exposed to natural irradiation, but owing to the growing use of ionizing radiations both in medicine and in industry, not to mention nuclear tests and their use as an argument of dissuasion, the irradiation of human beings is increasing daily. Radioactive contamination does remain latent, apart from acute cases, but this is where the danger lies since the consequences may not appear until long after the irradiation. Of all biological effects due to the action of radioelements the genetic risk is one of the most important, affecting the entire population and especially the generations to come. The risk of cancer and leukemia induction plays a substantial part also since a large number of people may be concerned, depending on the mode of contamination involved. All these long-term dangers do not of course exclude the various general or local effects to which the individual alone may be exposed and which sometimes constitute a threat to life. As a result the use of ionizing radiations must be limited and should only be involved if no other process can serve instead. The regulations governing radioelements must be stringent and their application strictly supervised for the better protection of man. This protection must be not only individual but also collective since pollution exists in air, water and land passes to plants and animals and finally reaches the last link in the food chain, man

  2. Mutans Streptococci Dose Response to Xylitol Chewing Gum

    OpenAIRE

    Milgrom, P.; Ly, K.A.; Roberts, M C; Rothen, M; Mueller, G.; Yamaguchi, D.K.

    2006-01-01

    Xylitol is promoted in caries-preventive strategies, yet its effective dose range is unclear. This study determined the dose-response of mutans streptococci in plaque and unstimulated saliva to xylitol gum. Participants (n = 132) were randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol 3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4 times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on modified Mitis Salivari...

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

    International Nuclear Information System (INIS)

    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

  4. Quantum Effects in Biological Systems

    CERN Document Server

    2016-01-01

    Since the last decade the study of quantum mechanical phenomena in biological systems has become a vibrant field of research. Initially sparked by evidence of quantum effects in energy transport that is instrumental for photosynthesis, quantum biology asks the question of how methods and models from quantum theory can help us to understand fundamental mechanisms in living organisms. This approach entails a paradigm change challenging the related disciplines: The successful framework of quantum theory is taken out of its low-temperature, microscopic regimes and applied to hot and dense macroscopic environments, thereby extending the toolbox of biology and biochemistry at the same time. The Quantum Effects in Biological Systems conference is a platform for researchers from biology, chemistry and physics to present and discuss the latest developments in the field of quantum biology. After meetings in Lisbon (2009), Harvard (2010), Ulm (2011), Berkeley (2012), Vienna (2013), Singapore (2014) and Florence (2015),...

  5. The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview

    International Nuclear Information System (INIS)

    A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings

  6. Biological radiation effects

    International Nuclear Information System (INIS)

    The stages of processes leading to radiation damage are studied, as well as, the direct and indirect mechanics of its production. The radiation effects on nucleic acid and protein macro moleculas are treated. The physical and chemical factors that modify radiosensibility are analysed, in particular the oxygen effects, the sensibilization by analogues of nitrogen bases, post-effects, chemical protection and inherent cell factors. Consideration is given to restoration processes by excision of injured fragments, the bloching of the excision restoration processes, the restoration of lesions caused by ionizing radiations and to the restoration by genetic recombination. Referring to somatic effects of radiation, the early ones and the acute syndrome of radiation are discussed. The difference of radiosensibility observed in mammalian cells and main observable alterations in tissues and organs are commented. Referring to delayed radiation effects, carcinogeneses, alterations of life span, effects on growth and development, as well as localized effects, are also discussed

  7. TESS-based dose-response using pediatric clonidine exposures

    International Nuclear Information System (INIS)

    Objective: The toxic and lethal doses of clonidine in children are unclear. This study was designed to determine whether data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) could be utilized to determine a dose-response relationship for pediatric clonidine exposure. Methods: 3458 single-substance clonidine exposures in children <6 years of age reported to TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a 'taste or lick' (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) μg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). Results: The logistic model describing medical outcome (P < 0.0001) included Log dose/kg (P 0.0000) and Certainty (P = 0.045). Conclusion: TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures

  8. Confidence bounds for nonlinear dose-response relationships.

    Science.gov (United States)

    Baayen, C; Hougaard, P

    2015-11-30

    An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve. It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated using a public dataset and simulations based on the Emax and sigmoid Emax models. PMID:26112765

  9. Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations.

    Science.gov (United States)

    Calabrese, Edward J

    2016-08-01

    This article provides the first extensive documentation of the dose response features of pre- and postconditioning. Pre- and postconditioning studies with rigorous study designs, using multiple doses/concentrations along with refined dose/concentration spacing strategies, often display hormetic dose/concentration response relationships with considerable generality across biological model, inducing (i.e., conditioning) agent, challenging dose treatment, endpoint, and mechanism. Pre- and postconditioning hormesis dose/concentration-response relationships are reported for 154 diverse conditioning agents, affecting more than 550 dose/concentration responses, across a broad range of biological models and endpoints. The quantitative features of the pre- and postconditioning-induced protective responses are modest, typically being 30-60% greater than control values at maximum, findings that are consistent with a large body (>10,000) of hormetic dose/concentration responses not related to pre- and postconditioning. Regardless of the biological model, inducing agent, endpoint or mechanism, the quantitative features of hormetic dose/concentration responses are similar, suggesting that the magnitude of response is a measure of biological plasticity. This paper also provides the first documentation that hormetic effects account for preconditioning induced early (1-3h) and delayed (12-72h) windows of protection. These findings indicate that pre- and postconditioning are specific types of hormesis. PMID:26757428

  10. Skull base chordomas: analysis of dose-response characteristics

    International Nuclear Information System (INIS)

    Objective: To extract dose-response characteristics from dose-volume histograms and corresponding actuarial survival statistics for 115 patients with skull base chordomas. Materials and Methods: We analyzed data for 115 patients with skull base chordoma treated with combined photon and proton conformal radiotherapy to doses in the range 66.6Gy - 79.2Gy. Data set for each patient included gender, histology, age, tumor volume, prescribed dose, overall treatment time, time to recurrence or time to last observation, target dose-volume histogram, and several dosimetric parameters (minimum/mean/median/maximum target dose, percent of the target volume receiving the prescribed dose, dose to 90% of the target volume, and the Equivalent Uniform Dose (EUD). Data were analyzed using the Kaplan-Meier survivor function estimate, the proportional hazards (Cox) model, and parametric modeling of the actuarial probability of recurrence. Parameters of dose-response characteristics were obtained using the maximum likelihood method. Results: Local failure developed in 42 (36%) of patients, with actuarial local control rates at 5 years of 59.2%. The proportional hazards model revealed significant dependence of gender on the probability of recurrence, with female patients having significantly poorer prognosis (hazard ratio of 2.3 with the p value of 0.008). The Wilcoxon and the log-rank tests of the corresponding Kaplan-Meier recurrence-free survival curves confirmed statistical significance of this effect. The Cox model with stratification by gender showed significance of tumor volume (p=0.01), the minimum target dose (p=0.02), and the EUD (p=0.02). Other parameters were not significant at the α level of significance of 0.05, including the prescribed dose (p=0.21). Parametric analysis using a combined model of tumor control probability (to account for non-uniformity of target dose distribution) and the Weibull failure time model (to account for censoring) allowed us to estimate

  11. Climatic and biological effects

    International Nuclear Information System (INIS)

    The ozone-climate problem has received considerable attention since concern was raised regarding possible threats to stratospheric ozone. Early climatic assessments of reduced ozone focused on the direct solar and longwave effects. Now a number of important feedback mechanisms are recognized as contributing significantly to indirect climatic effects. Although the focus in this chapter is on the climatic effect of reduced ozone, the discussion must include other trace gases as well. Many of the trace gases that interact photochemically to reduce ozone also have important radiative properties. Examples are chlorofluorocarbons (CFCl3 and CF2Cl2), nitrous oxide (N2O), and methane (CH4). Other gases, such as CO2, affect the temperature profile in the atmosphere, which can have an indirect effect on ozone through temperature-dependent reaction rates. The change in ozone, in turn, alters the change in temperature. The direct radiative effect of gases comes about through absorption of solar radiation and absorption and emission of longwave radiation (also referred to as thermal, terrestrial, or infrared radiation). The spectral distribution of solar and longwave radiation is shown. The principal gaseous absorbers of solar radiation are O2 and O3 in the stratosphere and H2O in the troposphere. As discussed in Chapter 2, ozone has absorption bands in the ultraviolet (uv) and visible regions of the solar spectrum. Water vapor absorbs primarily in the near-infrared spectral region

  12. Dose Response of Alanine Detectors Irradiated with Carbon Ion Beams

    DEFF Research Database (Denmark)

    Herrmann, Rochus; Jäkel, Oliver; Palmans, Hugo;

    2011-01-01

    Purpose: The dose response of the alanine detector shows a dependence on particle energy and type, when irradiated with ion beams. The purpose of this study is to investigate the response behaviour of the alanine detector in clinical carbon ion beams and compare the results with model predictions....... Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track-structure based alanine...... response model developed by J. Hansen and K. Olsen has been implemented in the Monte Carlo code FLUKA, and calculations were compared with experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for mono energetic beams. Measured depth...

  13. The influence of tube voltage and phantom size in computed tomography on the dose-response relationship of dicentrics in human blood samples

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the dose response relationship of dicentrics in human lymphocytes after CT scans at tube voltages of 80 and 140 kV. Blood samples from a healthy donor placed in tissue equivalent abdomen phantoms of standard, pediatric and adipose sizes were exposed at dose levels up to 0.1 Gy using a 64-slice CT scanner. It was found that both the tube voltage and the phantom size significantly influenced the CT scan-induced linear dose-response relationship of dicentrics in human lymphocytes. Using the same phantom (standard abdomen), 80 kV CT x-rays were biologically more effective than 140 kV CT x-rays. However, it could also be determined that the applied phantom size had much more influence on the biological effectiveness. Obviously, the increasing slopes of the CT scan-induced dose response relationships of dicentrics in human lymphocytes obtained in a pediatric, a standard and an adipose abdomen have been induced by scattering effects of photons, which strongly increase with increasing phantom size.

  14. Biological radiation effects

    International Nuclear Information System (INIS)

    Everyone is exposed to a complex mix of electromagnetic fields (EMF) of different frequencies that permeate our environment. Exposures to these EMF are increasing significantly as technology advances unabated and new applications are found. Technological progress in the broadest sense of the word has always been associated with various hazards and risks, both perceived and real. The industrial, commercial and household application on EMF is no exception. Throughout the world, the general public is concerned that exposure to EMF from such sources as high voltage power lines, broadcasting networks, mobile telephones and their base stations could lead to adverse health consequences, especially in children. As a result, the construction of new power lines and broadcasting and mobile telephone network has met with considerable opposition in many countries. Public exposure to EMF is regulated by a variety of voluntary and legal limits, together with various national safety standards. Guidelines are designed to avoid all identified hazards, from short and long term exposure, recommended limits. The aim of this paper is to report the summary of the actual scientific knowledge about the potential health effects and hazards due to man made EMF and the new tendencies of the social and political choices

  15. Biological effects of mutagenic agents

    International Nuclear Information System (INIS)

    There is an increasing body of evidence that mutagenic agents (biological, chemical and physical) play an important role in the etiology of human diseases. Mutations may occur in the germinal as well as in the somatic cells. Mutations of the germ cells may result on infertility or fertilization of damaged cells, the later leading to abortion or birth of a malformed fetus. Somatic-cells mutations may have various biological effects, depending on the period of the human life at which the mutation occurs. If it occurs during the prenatal life, a teratogenic or carcinogenic effect will be observed. If the somatic cell is damaged during the postnatal life, this will lead to neoplastic transformation. Therefore it is extremely important to know the mutagenic, teratogenic and carcinogenic effects of various biological, chemical and physical agents in order to eliminate them from our environment. (author). 13 refs, 4 figs, 1 tab

  16. Bayesian Dose-Response Modeling in Sparse Data

    Science.gov (United States)

    Kim, Steven B.

    This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a

  17. Limitations in dose-response and surrogate species methodologies for risk assessment of Cry toxins on arthropod natural enemies.

    Science.gov (United States)

    Paula, Débora P; Andow, David A; Bellinati, André; Timbó, Renata Velozo; Souza, Lucas M; Pires, Carmen S S; Sujii, Edison R

    2016-04-01

    Dose-response assays and surrogate species are standard methods for risk analysis for environmental chemicals. These assume that individuals within a species have unimodal responses and that a surrogate species can predict responses of other related taxa. We exposed immature individuals of closely related aphidophagous coccinellid predators, Cycloneda sanguinea and Harmonia axyridis, to Cry1Ac and Cry1F toxins through uniform and constant artificial tritrophic exposure through Myzus persicae aphids. Both toxins were detected in coccinellid pupae, with individual and interspecific variation. Uptake was significantly higher in H. axyridis than in C. sanguinea, both in the proportion of individuals and the concentrations per individual. We also observed bimodal uptake of the Cry toxins by H. axyridis, which indicated that some individuals had low bioaccumulation and some had high bioaccumulation. This suggests that standard dose-response assays need to be interpreted with caution and future assays should examine the modality of the responses. In addition, the similarity in the biological effects of the Cry toxins in the two predators was due to different biological exposure mechanisms. The majority of H. axyridis were exposed both internally and in the gut, while C. sanguinea was exposed primarily in the gut. Thus, despite their close phylogenetic relatedness, these species would not be good surrogates for each other and the surrogate species methodology should be tested more rigorously. PMID:26846212

  18. Marginal iodide deficiency and thyroid function: Dose-response analysis for quantitative pharmacokinetic modeling

    International Nuclear Information System (INIS)

    Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 μg/kg I to the base diet (∼25 μg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal + added I, Treatment 1: 1000 μg I/kg chow) to deficient (Treatment 5: 25 μg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation.

  19. The dose-response relationship for UV-tumorigenesis

    International Nuclear Information System (INIS)

    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.)

  20. Biological effectiveness of antiproton annihilation

    CERN Document Server

    Holzscheiter, Michael H.; Bassler, Niels; Beyer, Gerd; De Marco, John J.; Doser, Michael; Ichioka, Toshiyasu; Iwamoto, Keisuke S.; Knudsen, Helge V.; Landua, Rolf; Maggiore, Carl; McBride, William H.; Møller, Søren Pape; Petersen, Jorgen; Smathers, James B.; Skarsgard, Lloyd D.; Solberg, Timothy D.; Uggerhøj, Ulrik I.; Withers, H.Rodney; Vranjes, Sanja; Wong, Michelle; Wouters, Bradly G.

    2004-01-01

    We describe an experiment designed to determine whether or not the densely ionizing particles emanating from the annihilation of antiprotons produce an increase in “biological dose” in the vicinity of the narrow Bragg peak for antiprotons compared to protons. This experiment is the first direct measurement of the biological effects of antiproton annihilation. The experiment has been approved by the CERN Research Board for running at the CERN Antiproton Decelerator (AD) as AD-4/ACE (Antiproton Cell Experiment) and has begun data taking in June of 2003. The background, description and the current status of the experiment are given.

  1. Dose response curve of induction of MN in lymphocytes for energies Cs-137

    International Nuclear Information System (INIS)

    The determination of the dose-response curve is a crucial step to use the Micronucleus assay in Lymphocytes as a biological dosimeters. The most widely used fitting function is the linear-quadratic function. The coefficients are fitted by calibration data provided by irradiations of blood from healthy donors. In our case we performed the calibration curve corresponding to gamma radiation from Cesium-137 (660 keV). Doses ranged from 0 to 16 Gy. The fitting procedure used was the iteratively re weighted least square algorithm implemented in a Matlab routine. The results of the analysis of our data show that the dose-effect curve does not follow a linear-quadratic curve at high radiation doses, diminishing the quadratic parameters as dose increases. This can be interpreted as a micronucleus saturation effect beyond a certain dose level. We conclude that the MN assay with lymphocytes can be well characterized as a biological dosimeters up to a maximum dose of 4.5 Gy. (Author)

  2. Linear dose response curves in fungi and tradescantia

    International Nuclear Information System (INIS)

    heterozygosity (LOH) events occur because Clone 02 repairs both DSB and LCD by recombination. Clone 02 has a linear dose response for high LET radiation. Starting from the same initial yieId frequency, wild-types have a sublinear response. The sublinear response reflects a smoothly decreasing probability that 'pinks' are generated as a function of increasing high LET dose for wild-type but not Clone 02. This smoothly decreasing response would be expected for LOH in 'wild-type' humans. It reflects an increasing proportion of DNA damage being repaired by non-recombinational pathways and/or an increasing probability of cell death with increasing dose. Clone 02 at low doses and low dose rates of low LET radiation has a linear dose response, reflecting a 1/16 probability of a lesion leading to LOH, relative to high LET lesions. This differential is held to reflect: microdosimetric differences in energy deposition and, therefore, DNA damage by low and high LET radiations; the effects of lesion clustering after high LET on the probability of generating the end wild-types. While no observations have been made at very low doses and dose rates in wild-types, there is no reason to suppose that the low LET linear non-threshold dose response of Clone 02 is abnormal. The importance of the LOH somatic genetic end-point is that it reflects cancer risk in humans. The linear non-threshold low dose low LET response curves reflects either the probability that recombinational Holliday junctions are occasionally cleaved in a rare orientation to generate LOH, or the probability that low LET lesions include a small proportion of clustered events similar to high LET ionization or both. Calculations of the Poisson probability that two or more low LET lesions will be induced in the same target suggest that dose rate effects depend upon the coincidence of DNA lesions in the same target, and that the probability of LOH depends upon lesion and repair factors. But the slope of LOH in Clone 02 and all other

  3. Biological effects of ionizing radiation

    International Nuclear Information System (INIS)

    In this review radiation produced by the nuclear industry is placed into context with other sources of radiation in our world. Human health effects of radiation, derivation of standards and risk estimates are reviewed in this document. The implications of exposing the worker and the general population to radiation generated by nuclear power are assessed. Effects of radiation are also reviewed. Finally, gaps in our knowledge concerning radiation are identified and current research on biological effects, on environmental aspects, and on dosimetry of radiation within AECL and Canada is documented in this report. (author)

  4. Mahalanobis distance and variable selection to optimize dose response

    International Nuclear Information System (INIS)

    A battery of statistical techniques are combined to improve detection of low-level dose response. First, Mahalanobis distances are used to classify objects as normal or abnormal. Then the proportion classified abnormal is regressed on dose. Finally, a subset of regressor variables is selected which maximizes the slope of the dose response line. Use of the techniques is illustrated by application to mouse sperm damaged by low doses of x-rays

  5. 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". PMID:22574765

  6. Mutations induced in Tradescantia by small doses of X-rays and neutrons - Analysis of dose-response curves.

    Science.gov (United States)

    Sparrow, A. H.; Underbrink, A. G.; Rossi, H. H.

    1972-01-01

    Dose-response curves for pink somatic mutations in Tradescantia stamen hairs were analyzed after neutron and X-ray irradiation with doses ranging from a fraction of a rad to the region of saturation. The dose-effect relation for neutrons indicates a linear dependence from 0.01 to 8 rads; between 0.25 and 5 rads, a linear dependence is indicated for X-rays also. As a consequence the relative biological effectiveness reaches a constant value (about 50) at low doses. The observations are in good agreement with the predictions of the theory of dual radiation action and support its interpretation of the effects of radiation on higher organisms. The doubling dose of X-rays was found to be nearly 1 rad.

  7. Dose response relationship at low doses

    International Nuclear Information System (INIS)

    The data that have accrued in Hiroshima and Nagasaki on the effects of ionizing radiation on the developing human brain are reviewed. Effects considered are severe mental retardation, lowered IQ scores, decline in school performance, seizures, other neuropsychological effects, and small head size. All these factors may be related to radiation doses received by the mother during pregnancy. (L.L.) 3 figs., tab., 7 refs

  8. Efeito dose-resposta de fatores de risco para a doença isquêmica do coração Dose-response effect of risk factors to ischaemic heart disease

    Directory of Open Access Journals (Sweden)

    Suzana Alves de Moraes

    1996-10-01

    factors to ischaemic heart disease (IHD. However few of them have investigated the existence of a linear gradient related to the levels of these exposures and IHD. The effect of different levels of these exposures and IHD after adjusting for known confounders of effect, is assessed. The project was designed as a case-control study and the data were collected over one year from March/93 to February/94. The sample was composed of a total of 833 individuals of both genders aged 30-69 living in the city of S. Paulo, SP (Brazil, 280 of whom were compared with 553 controls (285 neighbourhood controls and 268 hospital controls. Logistic regression was the statistical method wold for the analysis of the data. The results showed a linear gradient for known duration of hypertension and daily number of cigarettes consumed. Although the variables duration of hypercholesterolemia and duration of the habit smoking presented statistically significant odds ratio in the respective strata there was no indication of a linear gradient. Some methodological issues are presented to explain this absence of a linear gradient for known duration of hypercholesterolemia and duration of the smoking habit. It is concluded that the dose response effect detected for known duration of hypertension and daily number of cigarettes consumed were independent of the presence of major risk factors ischaemic heart disease.

  9. Quantum Effects in Biological Systems

    Science.gov (United States)

    Roy, Sisir

    2014-07-01

    The debates about the trivial and non-trivial effects in biological systems have drawn much attention during the last decade or so. What might these non-trivial sorts of quantum effects be? There is no consensus so far among the physicists and biologists regarding the meaning of "non-trivial quantum effects". However, there is no doubt about the implications of the challenging research into quantum effects relevant to biology such as coherent excitations of biomolecules and photosynthesis, quantum tunneling of protons, van der Waals forces, ultrafast dynamics through conical intersections, and phonon-assisted electron tunneling as the basis for our sense of smell, environment assisted transport of ions and entanglement in ion channels, role of quantum vacuum in consciousness. Several authors have discussed the non-trivial quantum effects and classified them into four broad categories: (a) Quantum life principle; (b) Quantum computing in the brain; (c) Quantum computing in genetics; and (d) Quantum consciousness. First, I will review the above developments. I will then discuss in detail the ion transport in the ion channel and the relevance of quantum theory in brain function. The ion transport in the ion channel plays a key role in information processing by the brain.

  10. Deuterium effects in cancer biology

    International Nuclear Information System (INIS)

    Since its discovery many experiments were conducted for explaining the effects of deuterium on biological systems. It was observed, in many studies, that by increasing the deuterium concentration, structural, metabolic and functional alterations at different extents are produced, which can lead to organism's death. On the other hand effects of concentration reduction are much less studied. Existing data in literature, with regard to intrinsic deuterium reduction effects on different carcinomas are rather scarce. In vitro studies of deuterium level reduction has evidenced an inhibiting effect upon the cellular proliferation in different tumoral cellular lines: M14 cellular lines (human melanoma), PC3 (prostate cancer) and MCF7 (breast cancer). In vivo researches made on experimental tumours, have shown that the deuterium level reduction determines partial or complete regressions in xenotransplanted tumours, while in veterinary oncological clinic, partial or total tumoral regression were observed in different spontaneous tumours in dogs and cats. (authors)

  11. Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

    2011-01-01

    Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

  12. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity

    NARCIS (Netherlands)

    G. Koshy; A. Delpisheh; B.J. Brabin

    2011-01-01

    The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental questionnai

  13. The dose-response-relation of erythema of the domestic pig induced by UVC-radiation (254 nm)

    International Nuclear Information System (INIS)

    For domestic pigs the time-course and the dose-response-relationship of erythemal effective UVC-radiation was investigated. By the chromameter CR 300 (Minolta) the redness of the skin was measured, using the international L*a*b*-system. As UVC-source a germicidal lamp (TUV, Philips) was housed in a tube. The irradiance of the 10 zylindric holes were attenuated by a wire mash, changing the intensity along a logarithmic decrement. For the experiment 10 pigs were used. Each pig could be irradiated with 40 dose-steps. The redness of the marked skin-areas was not only determined once before the irradiation but also several times within 36 hours. The reaction of the skin of the pigs to UVC-radiation was different to human's. The time-course of the UVC-erythema was biphasical. The second erythema-maximum could not be explained by the pigmentation, which had just begun, but by an new increase of the reddening of the skin. No dose-response-correlation like the human's UVC-erythema could be detected. Therefore, the domestic pig can not be used as a human's photo-biological model for UVC. (author)

  14. Biological effects of electromagnetic fields

    International Nuclear Information System (INIS)

    The effects of electromagnetic (em) fields on biological systems were first observed and exploited well over a century ago. Concern over the possible health hazards of human exposure to such fields developed much later. It is now well known that excessive exposure to em fields may have in undesirable biological consequences. Standards were introduced to determine what constitute an excessive exposure and how to avoid it. Current concern over the issue of hazards stems mainly from recent epidemiological studies of exposed populations and also from the results of laboratory experiments in which whole animals are exposed in vivo or tissue and cell cultures exposed in vitro to low levels of irradiation. The underlying fear is the possibility of a causal relationship between chronic exposure to low field levels and some forms of cancer. So far the evidence does not add up to a firm statement on the matter. At present it is not known how and at what level, if at all, can these exposure be harmful to human health. This state of affair does not provide a basis for incorporating the outcome of such research in exposure standards. This paper will give a brief overview of the research in this field and how it is evaluated for the purpose of producing scientifically based standards. The emphasis will be on the physical, biophysical and biological mechanisms implicated in the interaction between em fields and biological systems. Understanding such mechanisms leads not only to a more accurate evaluation of their health implications but also to their optimal utilization, under controlled conditions, in biomedical applications. (author)

  15. Mutans Streptococci Dose Response to Xylitol Chewing Gum

    Science.gov (United States)

    Milgrom, P.; Ly, K.A.; Roberts, M.C.; Rothen, M.; Mueller, G.; Yamaguchi, D.K.

    2008-01-01

    Xylitol is promoted in caries-preventive strategies, yet its effective dose range is unclear. This study determined the dose-response of mutans streptococci in plaque and unstimulated saliva to xylitol gum. Participants (n = 132) were randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol 3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4 times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on modified Mitis Salivarius agar for mutans streptococci and on blood agar for total culturable flora. At 5 wks, mutans streptococci levels in plaque were 10x lower than baseline in G3 and G4 (P = 0.007/0.003). There were no differences in saliva. At 6 mos, mutans streptococci in plaque for G3 and G4 remained 10x lower than baseline (P = 0.007/0.04). Saliva for G3 and G4 was lower than baseline by 8 to 9x (P = 0.011/0.038). Xylitol at 6.44 g/day and 10.32 g/day reduces mutans streptococci in plaque at 5 wks, and in plaque and unstimulated saliva at 6 mos. A plateau effect is suggested between 6.44 g and 10.32 g xylitol/day. PMID:16434738

  16. Biological studies of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, J.H.

    1949-11-16

    This paper discusses procedures for research on biological effects of radiation, using mouse tissue: activation trace analysis including methods and proceedures for handling samples before during and after irradiation; methods and procedures for ion exchange study; method of separation and recovery of copper, iron, zinc, cobalt, pubidium and cesium. Also included are studies of trace elements with radioactive isotopes: the distribution of cobalt 60, zinc 65, and copper 64 in the cytoplasm and nuclei of normal mice and those with tumors. 16 figs., 2 tabs.

  17. Low level radiation: biological effects

    International Nuclear Information System (INIS)

    It is imperative that physicians and scientists using radiations in health care delivery continue to assess the benefits derived, vs. potential risk, to patients and radiation workers being exposed to radiation in its various forms as part of our health delivery system. Insofar as possible we should assure our patients and ourselves that the benefits outweigh the potential hazards involved. Inferences as to the possible biological effects of low level radiation are generally based on extrapolations from those effects observed and measured following acute exposures to considerably higher doses of radiation. Thus, in order to shed light on the question of the possible biological effects of low level radiation, a wide variety of studies have been carried out using cells in culture and various species of plant and animal life. This manuscript makes reference to some of those studies with indications as to how and why the studies were done and the conclusions that might be drawn there from. In addition reference is made to the handling of this information by scientists, by environmentalists, and by the news media. Unfortunately, in many instances the public has been misled by what has been said and/or written. It is hoped that this presentation will provide an understandable and reasonable perspective on the various appropriate uses of radiation in our lives and how such uses do provide significant improvement in our health and in our quality of life

  18. Estimation and uncertainty analysis of dose response in an inter-laboratory experiment

    Science.gov (United States)

    Toman, Blaza; Rösslein, Matthias; Elliott, John T.; Petersen, Elijah J.

    2016-02-01

    An inter-laboratory experiment for the evaluation of toxic effects of NH2-polystyrene nanoparticles on living human cancer cells was performed with five participating laboratories. Previously published results from nanocytoxicity assays are often contradictory, mostly due to challenges related to producing a reliable cytotoxicity assay protocol for use with nanomaterials. Specific challenges include reproducibility preparing nanoparticle dispersions, biological variability from testing living cell lines, and the potential for nano-related interference effects. In this experiment, such challenges were addressed by developing a detailed experimental protocol and using a specially designed 96-well plate layout which incorporated a range of control measurements to assess multiple factors such as nanomaterial interference, pipetting accuracy, cell seeding density, and instrument performance. Detailed data analysis of these control measurements showed that good control of the experiments was attained by all participants in most cases. The main measurement objective of the study was the estimation of a dose response relationship between concentration of the nanoparticles and metabolic activity of the living cells, under several experimental conditions. The dose curve estimation was achieved by imbedding a three parameter logistic curve in a three level Bayesian hierarchical model, accounting for uncertainty due to all known experimental conditions as well as between laboratory variability in a top-down manner. Computation was performed using Markov Chain Monte Carlo methods. The fit of the model was evaluated using Bayesian posterior predictive probabilities and found to be satisfactory.

  19. Biological effects of ionizing radiation

    International Nuclear Information System (INIS)

    It has been emphasised the importance of DNA as the main target for ionizing radiation, that can induce damage by its direct action on this molecule or by an indirect effect mediated by free-radicals generated by water radiolysis. Biological effects of ionizing radiation are influenced not only by the dose but also by the dose-rate and the radiation quality. Radiation induced damage, mainly DNA single and double strand breaks, is detected by molecular sensors which in turn trigger signalling cascades leading to cell cycle arrest to allow DNA repair or programmed cell death (apoptosis). Those effects related with cell death, named deterministic, exhibits a dose-threshold below which they are not observed. Acute radiation syndrome and radiological burns are examples of this kind of effects. Other radiation induced effects, called stochastic, are the consequence of cell transformation and do not exhibit a dose-threshold. This is the case of cancer induction and hereditary effects. The aim of this presentation is briefly describe the main aspects of deterministic and stochastic effects from the point of view of radiobiology and radio pathology. (author)

  20. Nonlinear dose-response relationships and inducible cellular defence mechanisms

    International Nuclear Information System (INIS)

    With the inclusion of inducible radioprotective mechanisms in a radiobiological state-vector model it was possible to explain plateaus in dose-response relationships for neoplastic transformation produced by in vitro irradiation of different cell lines with low-LET irradiation at high dose rates. The current study repeated the simulation of one data set that contains a plateau at mid doses. In contrast to earlier studies, the new one did not model the repair of double-strand breaks (DSBs) located in bulk DNA (likely via non-homologous end joining) as being inducible. Repair of specific DSBs located in actively transcribed genes was assumed to occur via homologous recombination and was considered to be inducible. This reduced the number of parameters that have to be determined by fitting the model to data. In addition, all types of radical scavengers were formerly considered to be inducible by radiation. This was redefined in the current work and the effectiveness of scavengers was implemented in a refined way. The current work investigated whether these and other model adjustments lead to an improved fit of the data set. (author)

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

    International Nuclear Information System (INIS)

    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

  2. Biological effect of fast neutrons

    International Nuclear Information System (INIS)

    The efficiency of fast neutrons of the energy range from 1.7 to 5 MeV in reducing the reticulocyte count and in diminishing the spleen weight was studied in male NMRI mice and compared with the effects of 250 kV X-rays. The neutron induced decrease of reticulocyte number in the peripheral blood is complete two days after irradiation. At this time even low doses cause a maximal effect. The relation between the rise of effect and the increase of exposure is great in the range of low doses and small in high doses. The relative biological effectiveness of neutrons in reducing the reticulocyte count is 2.5 after low doses and 1.2 after high doses. The spleen of irradiated mice shows a marked loss of weight, the lowest weight values are observed at the second day after irradiation. The relative effectiveness of neutrons in diminishing the spleen weight is 2.1 at low doses, the RBE decreases to 1.4 and rises again to 1.9 at higher doses. These results are compared with previous findings on mortality response and leucocyte and lymphocyte decrease in mice after neutron irradiation. Reticulocyte and lymphocyte count are found to be useful indicators for the detection and evaluation of neutron damage in the sublethal dose range. (orig.)

  3. Review of dose-response curves for acute antimigraine drugs

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2015-01-01

    calcitonin-gene related peptide receptor antagonists (telcagepant, MK-3207, BI 44370 TA and BMS-927711) in placebo-controlled trials were reviewed. In addition, dose-response curves for adverse events (AEs) were reviewed. Expert opinion: For most triptans, the dose-response curve for efficacy is flat......, there are many unmet needs. Although upcoming drugs may not be superior to triptans, migraine patients will potentially benefit greatly from these, especially patients who are triptan non-responders and patients with cardiovascular disease....

  4. Revised assessment of cancer risk to dichloromethane: part I Bayesian PBPK and dose-response modeling in mice.

    OpenAIRE

    Marino, Dale J.; Clewell, Harvey J.; Gentry, P. Robinan; Covington, Tammie R.; Hack, C. Eric; David, Raymond M.; Morgott, David A.

    2006-01-01

    KEYWORDS - CLASSIFICATION: analysis;Animals;Bayes Theorem;chemically induced;Carcinogens;Dose-Response Relationship,Drug;Environment;Inhalation Exposure;metabolism;methods;Markov Chains;mechanisms of carcinogenesis;Methylene Chloride;Mice;Models,Biological;Monte Carlo Method;Neoplasms;pharmacokinetics;Risk Assessment;Safety.

  5. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2013-01-15

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

  6. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    International Nuclear Information System (INIS)

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles

  7. Biological effects of ionizing radiation

    International Nuclear Information System (INIS)

    The efficient dose of ionizing radiation (I.R.), expressed in sievert is a weighting of the deposited energy (absorbed dose in grays) by factors that take into account the radiation hazard and tissues radiosensitivity. it is useful in radiation protection because it allows to add exposures to ionizing radiation of different nature. for low doses, it has no probabilistic value. The determinist effects of ionizing radiation are observed from thresholds of several hundred of milli sievert. The seriousness grows with the dose. The whole-body doses exceeding 8 Sv are always lethal. The radio-induced cancers are observed only for doses exceeding 100 to 200 mSv for adults, delivered at a self important dose rate. Their seriousness does not depend on the dose. Their appear fortuity (stochastic effect) with a various individual susceptibility, genetically determined. The number of eventual radio-induced cancers coming from the exposure of a high number of persons to low dose of ionizing radiation (<100 mSv) cannot be evaluated with a linear without threshold model. these models, however usually used, do not take into account the biological reality of cell defense mechanisms, tissues or whole body defense mechanisms, these one being different against low or high doses of ionizing radiation. Against low doses, the preponderant mechanism is the elimination of potentially dangerous damaged cells. Against high doses, the repair of damaged cells is imperative to preserve the tissue functions. It can lead to DNA repair errors (radio-induced mutations) and canceration. The radio-induced congenital malformations are effects with threshold. The radio-induced carcinogenesis in utero is a stochastic effect. The radio-induced hereditary congenital malformations have never been highlighted for man. (N.C.)

  8. The direct physico-molecular (nonenzyme) mechanism of hormesis and dose-response self-induced radioprotective effect at combined action of weak ionizing radiation and free radicals on DNA

    International Nuclear Information System (INIS)

    Complete text of publication follows. The time-dependent dynamics of depolymerisation and autorepairing of DNA at separated and combined action of weak and intensive ionizing radiation (including problems of long-distant DNA damage recognition, radiation antagonism and synergism at combined irradiation, low-dose radiation effects and the phenomenon of hormesis) are discussed. Investigations have been aimed at determining the conditions under which double breakages of DNA chains (owing to detrimental irradiation action) become self-eliminable. Nonenzyme mechanism of DNA self-reparation was studied for the first time in our works. The main result of ionizing radiation action upon biological system is the creation of double breaks of DNA macromolecules. The energy V(L) of interaction (long-distant stacking) between two end-pairs of DNA nucleotides on the opposite sites of double break are totally under the control of: a) Coulomb interaction of charges, distributed on a surfaces of these nucleotides; b) dispersion features of dielectric permeabilities of the nucleotides and intercellular salt-aqueous medium through all the range of frequencies (Van-der-Waals-like forces). It was shown that at low (natural) concentration η of hydrated electrons in intercellular liquid the energy of interaction of two end-pairs (AT-AT, CG-CG) has the anti-repair barrier V(L) > kT at L=5-7 A. If η is increasing the barrier is reducing. All other transversal end-pairs experience only attraction. Other results of irradiation are generation of hydrated electrons and heavy ions in intercellular medium. Formation of these electrons and ions influences the energy of interaction in two main ways - changing both the permeabilities ε(ω) and Coulomb interaction. From one hand irradiation leads to additional DNA breaks. From the other one irradiation leads to the controlled reducing of anti-repair barrier and possible double breaks autorepairing. The time-dependent dynamics of DNA

  9. Dose-response curve to salbutamol during acute and chronic treatment with formoterol in COPD

    Directory of Open Access Journals (Sweden)

    La Piana GE

    2011-07-01

    Full Text Available Giuseppe Emanuele La Piana¹, Luciano Corda², Enrica Bertella¹, Luigi Taranto Montemurro¹, Laura Pini¹, Claudio Tantucci¹¹Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, ²Prima Divisione di Medicina Interna, Spedali Civili, Brescia, ItalyBackground: Use of short-acting ß2-agonists in chronic obstructive pulmonary disease (COPD during treatment with long-acting ß2-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD.Methods: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose after a 1-week washout (baseline, 8 hours after the first administration of formoterol 12 µg (day 1, and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler. Peak expiratory flow, forced expiratory volume in one second (FEV1, forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve.Results: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV1, and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV1 dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001. Within each dose-response curve, FEV1 was different only at baseline and at day 1 (P < 0.001, when FEV1 was still greater at 800 µg than at 0 µg (P < 0.02. In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001, always being higher at 800 µg than at 0 µg (P < 0.05.Conclusion: In patients with stable COPD, the maximal effect

  10. A biological effectiveness study on chromosomal aberrations induced by fission neutrons versus 60Co γ-rays in human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Objective: Whole blood lymphocytes samples being exposed to neutrons of 18 MeV energy and 60Co γ-rays respectively, both good dose-response relationships and relative biological effectiveness (RBE) were derived. Methods: Heparinized whole blood samples were exposed to neutrons and 60Co γ-rays, respectively. Radiation doses were from 0.5 Gy to 3.0 Gy. Dose rate was 0.2 Gy/min. Unstable chromosomal aberrations dicentrics and centric rings (dic+r), the same as Micronuclei in binucleated cells, were scored. Relative biological effectiveness (RBE) values of dic+rand Micronucleus were derived. Results: Chromosomal aberrations (dic+r) and Micronucleus induced by either neutrons or 60Co γ-rays had a good dose-response relationship. RBE value of chromosomal aberrations, exposed neutrons at 0.5-3.0 Gy, ranged from 1.59 to 2.81, similarly, micronucleus from 1.23 to 2.14. Conclusion: linear-quadratic dose-response was found for the induction of dic+r and Micronucleus in human lymphocytes exposed in vitro to neutrons of 18 MeV energy. neutrons has higher biological effectiveness in low doses. (authors)

  11. Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Yuece, Ulkue Rabia, E-mail: ulkuyuce@hotmail.co [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Meric, Niyazi, E-mail: meric@ankara.edu.t [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Atakol, Orhan, E-mail: atakol@science.ankara.edu.t [Ankara University, Science Faculty, Department of Chemistry, 06100, Tandogan - Ankara (Turkey); Yasar, Fusun, E-mail: ab121310@adalet.gov.t [Council of Forensic Medicine, Ankara Branch, Ankara (Turkey)

    2010-08-15

    The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.

  12. Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses

    OpenAIRE

    Liu, Li; An, Min; Johnson, Ian R.; Lovett, John V.

    2003-01-01

    Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the alleloc...

  13. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

    OpenAIRE

    Johnston, Sara C.; Lin, Kenny L.; Twenhafel, Nancy A.; Raymond, Jo Lynne W.; Shamblin, Joshua D.; Wollen, Suzanne E.; Wlazlowski, Carly B.; Wilkinson, Eric R.; Botto, Miriam A.; Goff, Arthur J.

    2015-01-01

    Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-ex...

  14. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    Directory of Open Access Journals (Sweden)

    Matthew W. Wheeler

    2008-02-01

    Full Text Available Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD, fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data.

  15. Early radiation dose-response in lung: an ultrastructural study

    International Nuclear Information System (INIS)

    A systematic fine-structural study of dog lungs was undertaken to ascertain the radiation dose response in the lungs of large animals. The capillary endothelium appeared to be the initial site of the post-irradiation pulmonary damage. This subpheural response included diffuse septal thickening, fibrosis, edema, and reduced alveolar lumina. The deep parenchymal response involved perivascular fibrosis, which was associated with perivascular hyperplasia of Type II pneumocytes, increased number and sizes of lamellar bodies, increased production and release of lamellar surfactant. No changes of alveolar luminar size were noted. The most significant changes were observed in those dose zones exposed to greater than 2400 rad, suggesting the possibility of an identifiable dose-response relationship. Early detection of radiation pneumonitis by electron microscopy is demonstrated, and qualitative and quantitative correlation of injury with both postirradiation time and dose is presented

  16. Genotoxicity testing: moving beyond qualitative "screen and bin" approach towards characterization of dose-response and thresholds.

    Science.gov (United States)

    Pottenger, Lynn H; Gollapudi, B Bhaskar

    2010-01-01

    For more than 40+ years, genotoxicity data have been interpreted in a qualitative, binary mode; a chemical is considered either positive or negative for a response in the test system. Although dose-response information is sometimes used in this decision, it is not routine to obtain the amount of information needed to inform risk assessment, for example to determine no-observed-genotoxic-effect-levels, primarily due to the historical view of genotoxic responses as "linear, no-threshold." Only recently have researchers begun to address this issue through robust experimental designs and application of statistical models. A growing body-of-evidence supports the existence of response thresholds for a number of mutagenic agents, in vitro and in vivo. Clearly, simple observation of a "hockey-stick" dose-response curve is not sufficient to establish a threshold. Collection of robust empirical data must be supported with an analysis of biological plausibility for the observed threshold. In this context, a chemical-specific mode-of-action (MOA) approach, which identifies key events responsible for the observed mutagenic effect, is extremely valuable. Biomarkers of key events, providing qualitative and quantitative information, can be integrated in a weight-of-evidence-based assessment of genotoxicity data from multiple test systems and used to identify data gaps to resolve/reduce uncertainties during the risk assessment process. To this end, specific recommendations on study design and data analysis are proposed. As the Environmental Mutagen Society celebrates its 40th anniversary, the field of genetic toxicology is marking a milestone on the path to a new paradigm, using a MOA, data-driven approach to answer questions about thresholds for genotoxic agents. PMID:20806283

  17. Dose-response relationships and risk estimates for the induction of cancer due to low doses of low-LET radiation

    International Nuclear Information System (INIS)

    Risk estimates for radiation-induced cancer at low doses can be obtained only by extrapolation from the known effects at high doses and high dose rates, using a suitable dose-response model. The applicability of three different models, linear, sublinear and supralinear, are discussed in this paper. Several experimental studies tend to favour a sublinear dose-response model (linear-quadratic model) for low-LET radiation. However, human epidemiological studies do not exclude any of the dose-response relationships. The risk estimates based on linear and linear quadratic dose-response models are compared and it is concluded that, for low-LET radiation, the linear dose-response model would probably over-estimate the actual risk of cancer by a factor of two or more. (author)

  18. Human evidence on the shape of the dose-response curves for radiation carcinogenesis

    International Nuclear Information System (INIS)

    The carcinogenic effects of high levels of ionizing radiation are better understood than those of any other environmental agent. However, the somatic risk from low doses is highly disputed. The uncertainties stem from the fact that a direct estimation of small risks requires impracticably large samples. Therefore, risk estimates for low doses have to be derived indirectly by extrapolation from high exposure data and are heavily dependent on assumptions about the form of the dose-response curve. Although radiobiological theories tested on in vitro systems predict a quadratic term in the dose-response equation which should, at least for sparsely ionizing radiation, dominate the shape of the curve, the epidemiological data available cannot exclude the possibility of a pure linear relationship. In some cases, apparent thresholds may result from latent periods inversely related to dose. Besides depending on the quality of the radiation, the shape seems also to differ with the type of cancer induced. Studies on uranium miners, atomic bomb survivors and on irradiated patients are reviewed with emphasis on the shape of the dose-response. The credibility of the most publicized reports claiming a large cancer risk from low levels of radiation is assessed. The feasibility of a new study in an area of high natural background is explored. Finally, the influence of the uncertainties concerning the effect of low level radiation on future exposure limits set by regulatory bodies is discussed. (Auth.)

  19. Biological effectiveness of antiproton annihilation

    DEFF Research Database (Denmark)

    Holzscheiter, M.H.; Agazaryan, N.; Bassler, Niels;

    2004-01-01

    We describe an experiment designed to determine whether or not the densely ionizing particles emanating from the annihilation of antiprotons produce an increase in ‘‘biological dose’’ in the vicinity of the narrow Bragg peak for antiprotons compared to protons. This experiment is the first direct...

  20. Biological effects of high LET radiations

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masami [Nagasaki Univ. (Japan). Faculty of Pharmaceutical Sciences

    1997-03-01

    Biological effect of radiation is different by a kind of it greatly. Heavy ions were generally more effective in cell inactivation, chromosome aberration induction, mutation induction and neoplastic cell transformation induction than {gamma}-rays in SHE cells. (author)

  1. Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme

    International Nuclear Information System (INIS)

    Purpose: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I 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 cm3 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 boost

  2. Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mabuchi, Kiyohiko [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States)

    2012-12-01

    Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  3. Polymer gel dosimetry. The dose response for X-ray irradiation

    International Nuclear Information System (INIS)

    Polymer gel dosimetry has been considered a promising technique for clinical use, but this potential has not yet been fully realized in Japan. One reason may be because the commercialized gel detector, BANGTM gel, is expensive and it is only produced abroad. A second reason is the difficulty of controlling dose sensitivity of the gel so that it is stable under ordinary clinical conditions. In this work we introduce two types of gel detectors (MAG and PAG) which we produced in-house. First the method of fabrication of gel is presented in detail, then the dose responses of MAG and PAG for X-ray irradiation are evaluating for MRI and X-ray CT scanning. The MAG-type gel is useful in low contrast dosimetry because of the high sensitivity in its dose response (R2). The PAG-type gel is effective for dosimetry in multiple field irradiations because its dose response (CT value) has reproducibility independent of the different irradiation conditions. Finally, we summarize the potential for clinical use of polymer gel dosimetry with these gel detectors. (author)

  4. Quantitative Dose-Response Curves from Subcellular Lipid Multilayer Microarrays

    Science.gov (United States)

    Kusi-Appiah, A. E.; Lowry, T. W.; Darrow, E. M.; Wilson, K.; Chadwick, B. P.; Davidson, M. W.; Lenhert, S.

    2015-01-01

    The dose-dependent bioactivity of small molecules on cells is a crucial factor in drug discovery and personalized medicine. Although small-molecule microarrays are a promising platform for miniaturized screening, it has been a challenge to use them to obtain quantitative dose-response curves in vitro, especially for lipophilic compounds. Here we establish a small-molecule microarray assay capable of controlling the dosage of small lipophilic molecules delivered to cells by varying the sub-cellular volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. Features with sub-cellular lateral dimensions were found necessary to obtain normal cell adhesion with HeLa cells. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. We used the surface supported lipid volume information to obtain EC-50 values for the response of HeLa cells to three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. No significant toxicity was observed on the control cells surrounding the drug/lipid patterns, indicating lack of interference or leakage from the arrays. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which we explain in terms of cell-adhesion playing a more important role in the surface-based assay. The assay should be scalable to a density of at least 10,000 dose response curves on the area of a standard microtiter plate. PMID:26167949

  5. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-06-01

    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

  6. Doses and biological effect of ionizing radiation

    International Nuclear Information System (INIS)

    Basic values and their symbols as well as units of physical dosimetry are given. The most important information about biological radiation effects is presented. Polish radiation protection standards are cited. (A.S.)

  7. Maximum likelihood estimation for cytogenetic dose-response curves

    International Nuclear Information System (INIS)

    In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa[γd + g(t, tau)d2], where t is the time and d is dose. The coefficient of the d2 term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure

  8. Dose-responses from multi-model inference for the non-cancer disease mortality of atomic bomb survivors.

    Science.gov (United States)

    Schöllnberger, H; Kaiser, J C; Jacob, P; Walsh, L

    2012-05-01

    The non-cancer mortality data for cerebrovascular disease (CVD) and cardiovascular diseases from Report 13 on the atomic bomb survivors published by the Radiation Effects Research Foundation were analysed to investigate the dose-response for the influence of radiation on these detrimental health effects. Various parametric and categorical models (such as linear-no-threshold (LNT) and a number of threshold and step models) were analysed with a statistical selection protocol that rated the model description of the data. Instead of applying the usual approach of identifying one preferred model for each data set, a set of plausible models was applied, and a sub-set of non-nested models was identified that all fitted the data about equally well. Subsequently, this sub-set of non-nested models was used to perform multi-model inference (MMI), an innovative method of mathematically combining different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. This procedure thereby produces more reliable risk estimates based on a more comprehensive appraisal of model uncertainties. For CVD, MMI yielded a weak dose-response (with a risk estimate of about one-third of the LNT model) below a step at 0.6 Gy and a stronger dose-response at higher doses. The calculated risk estimates are consistent with zero risk below this threshold-dose. For mortalities related to cardiovascular diseases, an LNT-type dose-response was found with risk estimates consistent with zero risk below 2.2 Gy based on 90% confidence intervals. The MMI approach described here resolves a dilemma in practical radiation protection when one is forced to select between models with profoundly different dose-responses for risk estimates. PMID:22437350

  9. Biological effect of radioprotectors. 2. Biological effect of aminothiol radioprotectors

    International Nuclear Information System (INIS)

    The section describes about radio-protective effects on cells and animals, and suppressive effects of mutagenesis and carcinogenesis of aminothiols. Amifostine, NH2-(CH2)3-NH-(CH2)2-SPO3H2 (WR-2721, prodrug), WR-1065 (amifostine-SH form, active principle of WR-2721) and WR-33278 (S-S oxidized form of WR-1065) are mainly discussed. In cells exposed in vitro to 4 mM WR-1065, their survival rates are usually elevated regardless of their types after radiation treatment. In vivo, the author employs the administration dose of 400 mg/kg, which is 2/3 LD50 of amifostine. The prodrug is less toxic than the active form in vivo and reduces the mortality by radiation. Amifostine is an FDA-registered medical for reduction of xerostomia during radiotherapy of head and neck cancer, and of renal toxicity of cisplatin during chemotherapy of advanced ovarian cancer. Hypoxanthine phosphoribosyl transferase (HPRT) mutagenic assay in vitro has revealed anti-mutagenic effect of WR-1065 at 40 M, and also in vivo, the effect is seen in mice after irradiation of X-ray and neutron beam at lower administration doses than that used for lethality test mentioned above. WR-2721 at 400 mg/kg and another aminothiol (WR-151327) have anti-caricinogenic effects in mice against lymphoreticular tumors induced by γ-ray or neutron beam and in rats, at 100 mg/kg WR-2721, against hepatoma development and at 50 mg/kg, against mammary cancer. The compounds are shown to suppress the tumor metastasis in animal models. In vitro, WR-1065 has been shown to reduce the frequency of cell transformation after X-ray or neutron exposure. (T.I.)

  10. Biological Effects of Ionizing Radiation

    International Nuclear Information System (INIS)

    The aim of this work is to verify the existence of the adaptive response phenomenon induced by low doses of ionizing radiation in living cells.A wild-type yeast Saccharomyces cerevisiae (Baker's yeast) was chosen as the biological target.As a parameter to quantify the sensibility of the target to radiation, the Lethal Dose 50 (LD50 ) was observed. In our experimental condition a value of (60 ± 1) Gy was measured for LD50 with Dose Rate of (0.44 ± 0.03) Gy/min. The method employed to show up the adaptive response phenomenon consisted in exposing the sample to low ''conditioning'' doses, which would initiate these mechanisms. Later the samples with and without conditioning were exposed to higher ''challenging'' doses (such as LD50), and the surviving fractions were compared. In order to maximize the differences, the doses and the time between irradiations were varied. The best results were obtained with both a conditioning dose of (0.44 ± 0.03) Gy and a waiting time of 2 hs until the application of the challenging dose. Following this procedures the 80% of the conditioned samples has survived, after receiving the application of the LD50. The adaptive response phenomenon was also verified for a wide range of challenging doses

  11. Dose - Response Curves for Dicentrics and PCC Rings: Preparedness for Radiological Emergency in Thailand

    International Nuclear Information System (INIS)

    Establishing in-vitro dose calibration curves is important for reconstruction of radiation dose in the exposed individuals. The aim of this pioneering work in Thailand was to generate dose-response curves using conventional biological dosimetry: dicentric chromosome assay (DCA) and premature chromosome condensation (PCC) assay. The peripheral blood lymphocytes were irradiated with 137Cs at a dose rate of 0.652 Gy/min to doses of 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy for DCA technique, and 5, 10, 15, 20 and 25 Gy for PCC technique. The blood samples were cultured and processed following the standard procedure given by the IAEA with slight modifications. At least 500-1,000 metaphases or 100 dicentrics/ PCC rings were analyzed using an automated metaphase finder system. The yield of dicentrics with dose was fitted to a linear quadratic model using Chromosome Aberration Calculation Software (CABAS, version 2.0), whereas the dose-response curve of PCC rings was fitted to a linear relationship. These curves will be useful for in-vitro dose reconstruction and can support the preparedness for radiological emergency in the country.

  12. Development of Dose-Response Models to Predict the Relationship for Human Toxoplasma gondii Infection Associated with Meat Consumption.

    Science.gov (United States)

    Guo, Miao; Mishra, Abhinav; Buchanan, Robert L; Dubey, Jitender P; Hill, Dolores E; Gamble, H Ray; Jones, Jeffrey L; Du, Xianzhi; Pradhan, Abani K

    2016-05-01

    Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States. It is thought that a substantial portion of human T. gondii infections is acquired through the consumption of meats. The dose-response relationship for human exposures to T. gondii-infected meat is unknown because no human data are available. The goal of this study was to develop and validate dose-response models based on animal studies, and to compute scaling factors so that animal-derived models can predict T. gondii infection in humans. Relevant studies in literature were collected and appropriate studies were selected based on animal species, stage, genotype of T. gondii, and route of infection. Data were pooled and fitted to four sigmoidal-shaped mathematical models, and model parameters were estimated using maximum likelihood estimation. Data from a mouse study were selected to develop the dose-response relationship. Exponential and beta-Poisson models, which predicted similar responses, were selected as reasonable dose-response models based on their simplicity, biological plausibility, and goodness fit. A confidence interval of the parameter was determined by constructing 10,000 bootstrap samples. Scaling factors were computed by matching the predicted infection cases with the epidemiological data. Mouse-derived models were validated against data for the dose-infection relationship in rats. A human dose-response model was developed as P (d) = 1-exp (-0.0015 × 0.005 × d) or P (d) = 1-(1 + d × 0.003 / 582.414)(-1.479) . Both models predict the human response after consuming T. gondii-infected meats, and provide an enhanced risk characterization in a quantitative microbial risk assessment model for this pathogen. PMID:26477997

  13. Biological effects of proton radiation: an update

    International Nuclear Information System (INIS)

    Proton radiation provides significant dosimetric advantages when compared with gamma radiation due to its superior energy deposition characteristics. Although the physical aspects of proton radiobiology are well understood, biological and clinical endpoints are understudied. The current practice to assume the relative biological effectiveness of low linear energy transfer (LET) protons to be a generic value of about 1.1 relative to photons likely obscures important unrecognised differentials in biological response between these radiation qualities. A deeper understanding of the biological properties induced by proton radiation would have both radiobiological and clinical impact. This article briefly points to some of the literature pertinent to the effects of protons on tissue-level processes that modify disease progression, such as angiogenesis, cell invasion and cancer metastasis. Recent findings hint that proton radiation may, in addition to offering improved radio-therapeutic targeting, be a means to provide a new dimension for increasing therapeutic benefits for patients by manipulating these tissue-level processes. (authors)

  14. Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? ###SETAC

    Science.gov (United States)

    The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. Recently, claims have arisen tha...

  15. Dose-response relationships for radium-induced bone sarcomas

    International Nuclear Information System (INIS)

    The incidence of bone sarcomas among 3055 female radium-dial workers who entered the dial industry before 1950 was used to determine dose-response relationships for the induction of bone sarcomas by radium. Two subpopulations were analyzed: all measured cases who survived at last five years after the start of employment and all cases who survived at least two years after first measurement. The first constituted a group based on year of entry; it contained 1468 women who experienced 42 bone sarcomas; the expected number was 0.4. The second comprised a group based on first measurement; it contained 1257 women who experienced 13 bone sarcomas; the expected number was 0.2. The dose-response function, I = (C + αD + #betta#D2)e/sup -#betta#D/, and simplifications of this general form, were fit to each data set. Two functions, I = (C + αD + #betta#D2)e/sup -#betta#D/ and I = (C + #betta#D2)e/sup -#betta#D/, fit the data for year of entry (p greater than or equal to 0.05); both these functions and I = (C + αD) fit the data for first measurement. The function I = (C + #betta#D2)e/sup -#betta#D/ was used to predict the number of bone sarcomas in all other pre-1950 radium cases (medical, laboratory, and other exposure); fewer were actually observed than the fit of this function to the female dial workers predicted

  16. 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

  17. Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients

    Directory of Open Access Journals (Sweden)

    Coombes Jeff S

    2009-10-01

    Full Text Available Abstract Background Oxidative stress is associated with increased cardiovascular morbidity and mortality particularly in patients with end stage kidney disease. Although observational data from the general population has shown dietary antioxidant intake is associated with reduced cardiovascular morbidity and mortality, most clinical intervention trials have failed to support this relationship. This may be a consequence of not using an effective antioxidant dose and/or not investigating patients with elevated oxidative stress. The SPACE study, conducted in haemodialysis patients, reported that 800 IU/day of alpha tocopherol significantly reduced cardiovascular disease endpoints. A recent time course and dose response study conducted in hypercholesterolaemic patients that found 1600 IU/day of alpha tocopherol was an optimal dose. There is no such dose response data available for haemodialysis patients. Therefore the aim of this study is to investigate the effect of different doses of oral alpha tocopherol on oxidative stress in haemodialysis patients with elevated oxidative stress and the time taken to achieve this effect. Methods The study will consist of a time-course followed by a dose response study. In the time course study 20 haemodialysis patients with elevated oxidative stress will take either 1600 IU/day natural (RRR alpha tocopherol for 20 weeks or placebo. Blood will be collected every two weeks and analysed for a marker of oxidative stress (plasma F2-isoprostanes and alpha tocopherol. The optimum time period to significantly decrease plasma F2-isoprostanes will be determined from this study. In the dose response study 60 patients will be randomised to receive either placebo, 100, 200, 400, 800 or 1600 IU/day of natural (RRR alpha tocopherol for a time period determined from the time course study. Blood will be collected at baseline and every two weeks and analysed for plasma F2-isoprostanes and alpha tocopherol. It is hypothesised that

  18. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  19. Biological Effects of Irradiated Fats

    International Nuclear Information System (INIS)

    Rats were fed with a diet containing 20% of irradiated oils. If the oils were irradiated with 2.5 Mrad, there was no indication of detrimental effects during the course of 80 weeks. Oils irradiated with 10 Mrad, however, caused an increase in lethality after a lag period of 9 to 12 months. Irradiation with 50 Mrad caused weight losses after 24 weeks, disturbed liver function, and hypoproteinaemia, with a relative increase in gamma globulins. No animal of this group exceeded a life-span of 75 weeks. Irradiation with 100 Mrad caused immediate toxic symptoms and a high lethality. There is no indication that peroxides are responsible for the toxicity of the irradiated oils. Because of the high content of dimeric products in the irradiated oils, it is assumed that dimerization of fatty acids is the cause of damage. (author)

  20. Biological Effects Of Artificial Illumination

    Science.gov (United States)

    Corth, Richard

    1980-10-01

    We are increasingly being warned of the possible effects of so called "polluted" light, that is light that differs in spectral content from that of sunlight. We should be concerned, we are told, because all animals and plants have evolved under this natural daylight and therefore any difference between that illuminant and the artificial illuminants that are on the market today, is suspect. The usual presentation of the differences between the sunlight and the artificial illuminants are as shown in Figure 1. Here we are shown the spectral power distribution of sunlight and Cool White fluorescent light. The spectral power distributions of each have been normalized to some convenient wavelength so that each can be seen and easily compared on the same figure. But this presentation is misleading for one does not experience artificial illuminants at the same intensity as one experiences sunlight. Sunlight intensities are ordinarily found to be in the 8000 to 10,000 footcandle range whereas artificial illuminants are rarely experienced at intensity levels greater than 100 footcandles. Therefore a representative difference between the two types of illumination conditions is more accurately represented as in Figure 2. Thus if evolutionary adaptations require that humans and other animals be exposed to sunlight to ensure wellbeing, it is clear that one must be exposed to sunlight intensities. It is not feasible to expect that artificially illuminated environments will be lit to the same intensity as sunlight

  1. Biological effects of prenatal irradiation

    International Nuclear Information System (INIS)

    After large releases of radionuclides, exposure of the embryo or fetus can take place by external irradiation or uptake of radionuclies. The embryo and fetus are radiosensitive throughout prenatal development. The quality and extent of radiation effects depend on the development stage. During the preimplantation period (one to 10 days postconception, p.c.) a radiation exposure of at least 0.2 Gy can cause the death of the embryo. Malformations are only observed in rare cases when genetic predisposition exist. Macroscopic, anatomical malformations are induced only after irradiation during the major organogenesis (two to eight weeks p.c.). A radiation dose of about 0.2 Gy is a doubling dose for the malformation risks as extrapolated from experiments with rodents. The human embryo may be more radioresistant. During early fetogenesis (8-15 weeks p.c.) a high radiosensitivity exists for the developmental of the brain. Radiation doses of 1.0 Gy cause severe mental retardation in about 40% of the exposed fetuses. It must be taken into account that a radiation exposure during the fetal period can also induce cancer. It is generally assumed that the risk exists at about the same level as for children. (Author)

  2. The biological effectiveness of antiproton irradiation

    DEFF Research Database (Denmark)

    Holzscheiter, Michael H.; Bassler, Niels; Agazaryan, Nzhde;

    2006-01-01

    Background and purpose: Antiprotons travel through tissue in a manner similar to that for protons until they reach the end of their range where they annihilate and deposit additional energy. This makes them potentially interesting for radiotherapy. The aim of this study was to conduct the first...... ever measurements of the biological effectiveness of antiprotons. Materials and methods: V79 cells were suspended in a semi-solid matrix and irradiated with 46.7 MeV antiprotons, 48 MeV protons, or 60Co c-rays. Clonogenic survival was determined as a function of depth along the particle beams. Dose and...... particle fluence response relationships were constructed from data in the plateau and Bragg peak regions of the beams and used to assess the biological effectiveness. Results: Due to uncertainties in antiproton dosimetry we defined a new term, called the biologically effective dose ratio (BEDR), which...

  3. X-ray dose response of calcite-A comprehensive analysis for optimal application in TL dosimetry

    Science.gov (United States)

    Kalita, J. M.; Wary, G.

    2016-09-01

    The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO3) mineral has been studied in detail. Quantitative analysis on the dose response shows that the 573 K annealed sample showed sublinear dose response from 10 mGy to 1 Gy. The fading and reproducibility of this sample are also good enough for dosimetric application. However, a specific annealing treatment after irradiation shows some significant improvements in the dosimetric characteristics of the sample. The 773 K pre-annealed sample, after X-ray irradiation post-annealing at 340 K for 6 min provides linear dose response from 10 mGy to 3.60 Gy, very less fading and good reproducibility. Moreover, this sample after post-annealing at 380 K for 6 min shows linear dose response from 10 mGy to 5.40 Gy when analyzed from the ∼408 K thermoluminescence (TL) glow peak. Analysis of TL glow curves confirmed that the 1.30 eV trap center in calcite crystal is the most effective trapping site for dosimetric application.

  4. Biological Effect of Magnetic Field in Mice

    Institute of Scientific and Technical Information of China (English)

    Zhao-Wei ZENG

    2005-01-01

    Objective: To study the biological effect of magnetic field in mice bodies. Method: With a piece of permanent magnet embeded in mice bodies beside the femoral artery and vein to measure the electrophoretic velocity(um/s). Result: The magnetic field in mice bodies on the experiment group that the electrophoretic velocity is faster more than control and free group.Conclusion:The magnetic field in animal's body can raise the negative electric charges on the surface of erythrocyte to improve the microcirculation, this is the biological effect of magnetic field.

  5. Action spectra affect variability of the climatology of biologically effective ultraviolet radiation on cloud-free days

    International Nuclear Information System (INIS)

    Action spectrum (AS) describes the relative effectiveness of ultraviolet (UV) radiation in producing biological effects and allows spectral UV irradiance to be weighted in order to compute biologically effective UV radiation (UVBE). The aim of this research was to study the seasonal and latitudinal distribution over Europe of daily UVBE doses responsible for various biological effects on humans and plants. Clear sky UV radiation spectra were computed at 30-min time intervals for the first day of each month of the year for Rome, Potsdam and Trondheim using a radiative transfer model fed with climatological data. Spectral data were weighted using AS for erythema, vitamin D synthesis, cataract and photo-keratitis for humans, while the generalised plant damage and the plant damage AS were used for plants. The daily UVBE doses for the above-mentioned biological processes were computed and are analysed in this study. The patterns of variation due to season (for each location) and latitude (for each date) resulted as being specific for each adopted AS. The biological implications of these results are briefly discussed highlighting the importance of a specific UVBE climatology for each biological process. (authors)

  6. Application of the Key Events Dose-response Framework to Folate Metabolism.

    Science.gov (United States)

    Hu, Jing; Wang, Bing; Sahyoun, Nadine R

    2016-06-10

    Folate is a vitamin that plays a role as a cofactor and coenzyme in many essential reactions. These reactions are interrelated and any change in folate homeostasis could affect other reactions. With food fortified with folic acid, and use of multivitamin, unmetabolized folic acid (UMFA) has been detected in blood circulation, particularly among older adults. This has raised concern about the potential harmful effect of high folic acid intake and UMFA on health conditions such as cognitive dysfunction and cancer. To examine what is known about folate metabolism and the release of circulating UMFA, the Key Events Dose-Response Framework (KEDRF) was used to review each of the major key events, dose-response characteristics and homeostatic mechanisms of folate metabolism. The intestine, liver and kidneys each play essential roles in regulating body folate homeostasis. But the determining event in folate metabolism leading to the release of UMFA in circulation appears to be the saturation of dihydrofolate reductase in the liver. However, at each of the key events in folate metabolism, limited information is available on threshold, homeostatic regulation and intracellular effects of folic acid. More studies are needed to fill in the knowledge gaps for quantitatively characterizing the dose-effect relationship especially in light of the call for extending folate fortification to other foods. PMID:25674817

  7. Biological effectiveness of neutrons: Research needs

    Energy Technology Data Exchange (ETDEWEB)

    Casarett, G.W.; Braby, L.A.; Broerse, J.J.; Elkind, M.M.; Goodhead, D.T.; Oleinick, N.L.

    1994-02-01

    The goal of this report was to provide a conceptual plan for a research program that would provide a basis for determining more precisely the biological effectiveness of neutron radiation with emphasis on endpoints relevant to the protection of human health. This report presents the findings of the experts for seven particular categories of scientific information on neutron biological effectiveness. Chapter 2 examines the radiobiological mechanisms underlying the assumptions used to estimate human risk from neutrons and other radiations. Chapter 3 discusses the qualitative and quantitative models used to organize and evaluate experimental observations and to provide extrapolations where direct observations cannot be made. Chapter 4 discusses the physical principles governing the interaction of radiation with biological systems and the importance of accurate dosimetry in evaluating radiation risk and reducing the uncertainty in the biological data. Chapter 5 deals with the chemical and molecular changes underlying cellular responses and the LET dependence of these changes. Chapter 6, in turn, discusses those cellular and genetic changes which lead to mutation or neoplastic transformation. Chapters 7 and 8 examine deterministic and stochastic effects, respectively, and the data required for the prediction of such effects at different organizational levels and for the extrapolation from experimental results in animals to risks for man. Gaps and uncertainties in this data are examined relative to data required for establishing radiation protection standards for neutrons and procedures for the effective and safe use of neutron and other high-LET radiation therapy.

  8. Biological effectiveness of neutrons: Research needs

    International Nuclear Information System (INIS)

    The goal of this report was to provide a conceptual plan for a research program that would provide a basis for determining more precisely the biological effectiveness of neutron radiation with emphasis on endpoints relevant to the protection of human health. This report presents the findings of the experts for seven particular categories of scientific information on neutron biological effectiveness. Chapter 2 examines the radiobiological mechanisms underlying the assumptions used to estimate human risk from neutrons and other radiations. Chapter 3 discusses the qualitative and quantitative models used to organize and evaluate experimental observations and to provide extrapolations where direct observations cannot be made. Chapter 4 discusses the physical principles governing the interaction of radiation with biological systems and the importance of accurate dosimetry in evaluating radiation risk and reducing the uncertainty in the biological data. Chapter 5 deals with the chemical and molecular changes underlying cellular responses and the LET dependence of these changes. Chapter 6, in turn, discusses those cellular and genetic changes which lead to mutation or neoplastic transformation. Chapters 7 and 8 examine deterministic and stochastic effects, respectively, and the data required for the prediction of such effects at different organizational levels and for the extrapolation from experimental results in animals to risks for man. Gaps and uncertainties in this data are examined relative to data required for establishing radiation protection standards for neutrons and procedures for the effective and safe use of neutron and other high-LET radiation therapy

  9. A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

    Science.gov (United States)

    Wells, Thomas G.; Shahinfar, Shahnaz; Massaad, Rachid; Dankner, Wayne M.; Lam, Chun; Santoro, Emanuela Palumbo; McCrary Sisk, Christine; Blaustein, Robert O.

    2014-01-01

    Background and objectives Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6–16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years. Design, setting, participants, & measurements This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension. Patients were randomized to losartan at the following dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day maximum dosage, not exceeding 100 mg/d, which was not one of the three original doses offered at randomization) at weeks 3, 6, and 9 for patients who did not attain their goal BP and were not taking the highest dose. Dose response was evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared with baseline. Adverse events (AEs) were recorded throughout. Results Of the 101 patients randomized, 99 were included in the analysis (low dose, n=32; medium dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose-response relationship was established by the slope analysis on SBP (P=0.75) or DBP (P=0.64). The BP-lowering effect was observed throughout the 2-year extension. The incidence of AEs was low and comparable between groups. Conclusions Hypertensive children aged 6 months to 6 years treated with losartan 0.1–0.7 mg/kg per day had clinically significant decreases from baseline in SBP and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up to 1.4 mg/kg per day, was well tolerated. PMID:24875194

  10. Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.; Pierce, P.A.

    1997-09-04

    Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.

  11. RELATIVE BIOLOGICAL EFFECTIVENESS IN A PROTON SOBP

    Czech Academy of Sciences Publication Activity Database

    Vachelová, Jana; Michaelidesová, Anna; Litvinchuk, Alexandra; Vondráček, V.; Davídková, Marie

    Vol. 34. Bratislava : SMU - Faculty of Public Health, 2014. s. 121-121. ISBN 978-80-89384-08-2. [XXXVI.Dny radiační ochrany. 10.11.2014-14.11.2014, Poprad] Institutional support: RVO:61389005 Keywords : relative biological effectiveness * Spread-Out Bragg Peak * linear energy transfer Subject RIV: BO - Biophysics

  12. Biological radiation effects and radioprotection standards

    International Nuclear Information System (INIS)

    In this report, after recalling the mode of action of ionizing radiations, the notions of dose, dose equivalents and the values of natural irradiation, the author describes the biological radiation effects. Then he presents the ICRP recommendations and their applications to the french radioprotection system

  13. Exploiting Allee effects for managing biological invasions

    Czech Academy of Sciences Publication Activity Database

    Tobin, P. C.; Berec, Luděk; Liebhold, A. M.

    2011-01-01

    Roč. 14, č. 6 (2011), s. 615-624. ISSN 1461-023X Grant ostatní: National Centre for Ecological Analysis and Synthesis(US) EF-0553768 Institutional research plan: CEZ:AV0Z50070508 Keywords : Allee dynamics * biological invasions * component Allee effect Subject RIV: EH - Ecology, Behaviour Impact factor: 17.557, year: 2011

  14. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints.

    Science.gov (United States)

    Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B; George, Kerry A; Cucinotta, Francis A

    2016-01-01

    The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed. PMID:27111667

  15. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

    Science.gov (United States)

    Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.; George, Kerry A.; Cucinotta, Francis A.

    2016-01-01

    The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE’s using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE’s are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE’s against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed. PMID:27111667

  16. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints.

    Directory of Open Access Journals (Sweden)

    Eliedonna Cacao

    Full Text Available The biological effects of high charge and energy (HZE particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (10 are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.

  17. Development of a mid-head radiation dose response function

    International Nuclear Information System (INIS)

    Calculations have been made of the incident neutron and gamma-ray absorbed dose response as a function of energy in the mid-head position of a phantom model. The calculations were performed with the DOT discrete ordinates transport code in the adjoint mode using co-axial cylinders to represent the head and torso. Results, given in a coupled 37-neutron-group, 21-gamma-ray-group structure (37/21) and a 22-neutron-group, 18-gamma-ray-group structure (22/18), are compared with previously obtained results. The mid-head response is less than the conventional radiation protection fluence-to-dose factors which are based on maximum phantom values. In the case of a fission source in air the neutron dose is about a factor of 4 less, and the secondary gamma-ray dose is about a factor of 1.5 less. For a fusion source the neutron dose ratio varies from about 1.9 at close range to about 3. The gamma-ray dose ratio is about the same as for the fission source. Tables of the various response functions are presented in the Appendix A

  18. Dose-response behavior of the bacterium Vibrio fischeri exposed to pharmaceuticals and personal care products.

    Science.gov (United States)

    Ortiz de García, Sheyla; García-Encina, Pedro A; Irusta-Mata, Rubén

    2016-01-01

    The presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a real and widespread concern in recent years. Therefore, the primary goal of this study was to investigate 20 common and widely used PPCPs to assess their individual and combined effect on an important species in one trophic level, i.e., bacteria. The ecotoxicological effects of PPCPs at two different concentration ranges were determined in the bacterium Vibrio fischeri using Microtox(®) and were statistically analyzed using three models in the GraphPad Prism 6 program for Windows, v.6.03. A four-parameter model best fit the majority of the compounds. The half maximal effective concentration (EC50) of each PPCP was estimated using the best-fitting model and was compared with the results from a recent study. Comparative analysis indicated that most compounds showed the same level of toxicity. Moreover, the stimulatory effects of PPCPs at environmental concentrations (low doses) were assessed. These results indicated that certain compounds have traditional inverted U- or J-shaped dose-response curves, and 55% of them presented a stimulatory effect below the zero effect-concentration point. Effective concentrations of 0 (EC0), 5 (EC5) and 50% (EC50) were calculated for each PPCP as the ecotoxicological points. All compounds that presented narcosis as a mode of toxic action at high doses also exhibited stimulation at low concentrations. The maximum stimulatory effect of a mixture was higher than the highest stimulatory effect of each individually tested compound. Moreover, when the exposure time was increased, the hormetic effect decreased. Hormesis is being increasingly included in dose-response studies because this may have a harmful, beneficial or indifferent effect in an environment. Despite the results obtained in this research, further investigations need to be conducted to elucidate the behavior of PPCPs in aquatic environments. PMID:26518677

  19. Nuclear energy: biological effects and environmental impact

    International Nuclear Information System (INIS)

    This thesis is concerned with the large development of nuclear power plants and the recent nuclear catastrophe which has made clear how the hazards resulting from radioactivity affect public health and the environment. Environmental effects of nuclear power plants operating in normal conditions are small, but to obtain nuclear power plants of reduced radioactivity, optimization of their design, construction, operation and waste processing plays a decisive role. Biological effects of ionizing radiations and environmental impacts of Nuclear Power plants are developed

  20. II. Biological studies of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, J.H.

    1948-05-24

    With the completion of the 184 inch cyclotron in Berkeley and the successful construction of a deflector system, it was possible to bring the 190 Mev deuteron and the 380 Mev alpha beams out into the air and to begin a study of the effects of high-energy deuteron beams by direct irradiation of biological specimens. The direct biological use of deuteron beams was attempted earlier in Berkeley by Marshak, MacLeish, and Walker in 1940. These and other investigators have been aware for some time of the potential usefulness of high energy particle beams for radio-biological studies and their suitability for biological investigations. R.R. Wilson advanced the idea of using fast proton beams to deliver radiation and intervening tissues. R.E. Zirkle pointed out that such particle beams may be focused or screened until a cross-section of the beam is small enough to study effects of irradiation under the microscope on single cells or on parts of single cells. This article gives an overview of the radiological use of high energy deuteron beams, including the following topics: potential uses of high energy particle beams; experiments on the physical properties of the beam; lethal effect of the deuteron beam on mice.

  1. Lunar biological effects and the magnetosphere.

    Science.gov (United States)

    Bevington, Michael

    2015-12-01

    The debate about how far the Moon causes biological effects has continued for two millennia. Pliny the Elder argued for lunar power "penetrating all things", including plants, fish, animals and humans. He also linked the Moon with tides, confirmed mathematically by Newton. A review of modern studies of biological effects, especially from plants and animals, confirms the pervasive nature of this lunar force. However calculations from physics and other arguments refute the supposed mechanisms of gravity and light. Recent space exploration allows a new approach with evidence of electromagnetic fields associated with the Earth's magnetotail at full moon during the night, and similar, but more limited, effects from the Moon's wake on the magnetosphere at new moon during the day. The disturbance of the magnetotail is perhaps shown by measurements of electric fields of up to 16V/m compared with the usual electromagnetic radiation are known to affect animals and 10-20% of the human population. There is now evidence for mechanisms such as calcium flux, melatonin disruption, magnetite and cryptochromes. Both environmental and receptor variations explain confounding factors and inconsistencies in the evidence. Electromagnetic effects might also account for some evolutionary changes. Further research on lunar biological effects, such as acute myocardial infarction, could help the development of strategies to reduce adverse effects for people sensitive to geomagnetic disturbance. PMID:26462435

  2. Dose-response model of murine typhus (Rickettsia typhi: time post inoculation and host age dependency analysis

    Directory of Open Access Journals (Sweden)

    Tamrakar Sushil B

    2012-03-01

    Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.

  3. Biological effects of inhaled radionuclides. A report of a task group of Committee 1 of the International Commission on Radiological Protection. Adopted by the Commission in May 1979

    International Nuclear Information System (INIS)

    This report focuses on various types of radionuclides that may be inhaled and deposited in the respiratory tract. One of the primary goals of this ICRP Task Group is to assess specifically the biological implications of inhaled plutonium. Because other transuranics are becoming more abundant, information on americium, curium and einsteinium is included. Data are also included from studies of polonium and of several beta-gamma emitting isotopes. The Task Group evaluated most of the data on the biological effects of inhaled radionuclides in experimental animals to identify the tissues at risk and to assess possible dose-response relationships. Few data from human cases of inhaled radionuclides are available for this assessment. The biological effects of nonradioactive air pollutants were also considered to provide the perspective that all air pollutants can have a deleterious effect on human life and to emphasize the possibility for combined or synergistic effects of nonradioactive and radioactive substances on the respiratory tract. (author)

  4. Dose response of F center optical absorption in LiF:Mg,Ti (TLD-100)

    International Nuclear Information System (INIS)

    Optical absorption (OA) of nominally pure single crystal LiF following beta irradiation was measured in order to estimate, the energy and width of the dominant F-band with minimum interference from dopant-related bands. The OA dose response of LiF:Mg,Ti was measured to 30,000 Gy, a level of dose sufficiently high to observe total saturation of the F band, which, we believe, reduces uncertainty in the estimation of the dose filling constant. The dose filling constants for the OA bands associated with the trapping center (4 eV) and competitive center (5.45 eV) responsible for the major dosimetric TL glow peak 5 were also determined. The results of these studies will be used in the framework of a kinetic model which includes the effects of radiation created defects and which will aid in the investigation of the capability of Track Structure Theory to predict OA heavy charged particle (HCP) relative efficiencies. - Highlights: • The energy and width of the F-band in LiF are estimated. • OA dose response was extended to high levels of dose including deconvolution. • Dose filling constants of the major OA bands were determined

  5. Dose-response relationship for lung cancer induction at radiotherapy dose

    International Nuclear Information System (INIS)

    Cancer induction after radiation therapy is a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the treated patient. Currently there is large uncertainty about the shape of the dose-response relationship for carcinogenesis for most cancer types at high dose levels. In this work a dose-response relationship for lung cancer is derived based on (i) the analysis of lung 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. The fitted model parameters for an α/β = 3 Gy were α = 0.061Gy-1 and R = 0.84. The value for α is in agreement with analysis of normal tissue complications of the lung after radiation therapy. The repopulation/repair parameter R is large, but seems to be characteristic for lung tissue which is sensitive with regard to fractionation. Lung cancer risk is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 15 Gy and drops off only slightly at larger doses. The predicted EAR for lung after radiotherapy of Hodgkin's disease is 18.4/10000PY which can be compared to the findings of several epidemiological studies were EAR for lung varies between 9.7 and 21.5/10000PY. (orig.)

  6. Thermoluminescence from igneous and natural hydrothermal vein quartz: dose response after optical bleaching

    International Nuclear Information System (INIS)

    We studied optical bleaching and gamma dose response of primary quartz isolated from volcanic and granitic host rocks as well as from pegmatites and hydrothermal veins using thermoluminescence (TL). We attempted to isolate the TL signature of these individual types of quartz so that improved analysis of the TL behaviour of composite sedimentary quartz mixtures is possible. We have identified the following aspects of quartz TL in these samples: (1) large variation in TL residuals after extensive bleaching; (2) shifts in glow curve peak temperatures during bleaching and gamma dose apparently related to 2nd order TL kinetics; (3) differences in TL sensitivity to gamma dose among samples; (4) supralinear dose response of both a 230oC TL peak and a germanium EPR signal only in the pegmatitic quartz samples; and (5) the volcanic and pegmatitic samples had generally higher TL sensitivity to gamma dose than did the granitic or hydrothermal samples. We concluded that (1), (2) and (3) could contribute to enhanced scatter in routine TL dating of sediments composed of mixed fractions of different quartz types, but that none of the effects observed appear to introduce any unforeseen sources of error into ED determinations using any of the standard sediment dating methods. (author)

  7. Dose response in radiation-induced human carcinogenesis: accumulated data do not yet solve the enigma

    International Nuclear Information System (INIS)

    The carcinogenic effects of high levels of ionizing radiation are better understood than those of any other environmental agent. However, the somatic risk from low doses is highly disputed. The uncertainties stem from the fact that due to a multitude of confounding factors a direct estimation of small risks requires impracticably large samples. Therefore, risk estimates for low doses have to be derived indirectly by extrapolation from high-exposure data and are heavily dependent on assumptions about the shape of the dose-response curve. Although radiobiological theories tested mostly on in vitro systems predict a quadratic term in the dose-response equation, which should dominate the shape of the curve at least for sparsely ionizing radiation, the epidemiological data available are not yet sufficient to exclude the possibility of a purely linear relationship. In some cases, apparent thresholds may result from latent periods inversely related to dose. Besides depending on the quality of the radiation, the shape also seems to differ with the type of cancer induced. The huge epidemiological data base on atomic bomb survivors, irradiated patients, miners, and other exposed groups can most consistently be fitted to a linear quadratic model. For lung cancer in miners resulting from high linear energy transfer alpha radiation and for female breast cancer, the linear component seems to be dominant

  8. Optimal designs for dose-response models with restricted design spaces

    OpenAIRE

    Dette, Holger; Biedermann, Stefanie; Zhu, Wei

    2004-01-01

    In dose-response studies, the dose range is often restricted due to concerns over drug toxicity and/or efficacy. We derive optimal designs for estimating the underlying dose-response curve for a restricted or unrestricted dose range with respect to a broad class of optimality criteria. The underlying curve belongs to a diversified set of link functions suitable for the dose response studies and having a common canonical form. These include the fundamental binary response models -- t...

  9. Nonlinear dose response model with repair and repair suppression

    International Nuclear Information System (INIS)

    In March 1996, the Health Physics Society issued a position statement supporting a nonlinear threshold (NLT) concept for radiation risk at low-dose/low-dose-rate (LD/LDR) levels. This action was after receipt of an overwhelming consensus from world-renown radiobiologists and is contrary to the opinions of the United Nations Scientific Committee on Effects of Atomic Radiation, the National Research Council Committee on the Biological Effects of Ionizing Radiations, and U.S. Environmental Protection Agency. Alvarez and others have called for a new NLT model for radiation risk. Two mathematical models have historically been used to describe cell survival experimental results. Each provides the ability to account for the shoulder observed in cell survival curves, predominantly for low-linear energy transfer (LET) radiation, and the wide variation in radio sensitivity of cell species and particular phase of the mitotic cycle. Only Kellerer and Rossi, Elkind and Whitmore, and Green and Burki have proposed modified models explicitly incorporating radiobiological repair and departing from LNT. None of these were subsequently used with any extent of success in cell survival analysis. The author reports initial work on a program to reexamine radiobiology research exhibiting repair processes at LD/LDR levels

  10. Cumulative lognormal distributions of dose-response vs. dose distributions

    International Nuclear Information System (INIS)

    A review of the author's findings over four decades will show that the lognormal probability density function can be fit to many types of positive-variate radiation measurement and response data. The cumulative lognormal plot on probability vs. logarithmic coordinate graph paper can be shown to be useful in comparing trends in exposure distributions or responses under differing conditions or experimental parameters. For variates that can take on only positive values, such a model is more natural than the 'normal' (Gaussian) model. Such modeling can also be helpful in elucidating underlying mechanisms that cause the observed data distributions. It is important, however, to differentiate between the cumulative plot of a dose distribution, in which successive percentages of data are not statistically independent, and the plots of dose-response data for which independent groups of animals or persons are irradiated or observed for selected doses or dose intervals. While independent response points can often be best fitted by appropriate regression methods, the density functions for cumulative dose or concentration distributions must be fit by particular maximum likelihood estimates from the data. Also, as indicated in the texts by D.J. Finney and by R.O. Gilbert, for example, a simple plot of such data on available probability (or probit) vs. log scale graph paper will quickly show whether an adequate representation of the data is a lognormal function. Processes that naturally generate lognormal variates are sometimes estimated by statistics that follow the lognormal straight line for a cumulative plot on a probability vs. log scale; on the other hand, sometimes the statistics of interpretation follow such a line only over a certain range. Reported examples of lognormal occupational exposure distributions include those in some facilities in which roundoff biases were removed for some years. However, for a number of exposure distributions at licensed facilities in the

  11. Shared Dosimetry Error in Epidemiological Dose-Response Analyses

    Science.gov (United States)

    Stram, Daniel O.; Preston, Dale L.; Sokolnikov, Mikhail; Napier, Bruce; Kopecky, Kenneth J.; Boice, John; Beck, Harold; Till, John; Bouville, Andre

    2015-01-01

    Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed. PMID:25799311

  12. Shared Dosimetry Error in Epidemiological Dose-Response Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Stram, Daniel; Preston, D. L.; Sokolnkov, Mikhail; Napier, Bruce A.; Kopecky, Kenneth; Boice, John; Beck, Harold L.; Till, John E.; Bouville, A.

    2015-03-23

    Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. Use of these methods for several studies, including the Mayak Worker Cohort and the U.S. Atomic Veterans Study, is discussed.

  13. Shared dosimetry error in epidemiological dose-response analyses

    International Nuclear Information System (INIS)

    Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of 'possible' dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed

  14. Shared dosimetry error in epidemiological dose-response analyses.

    Directory of Open Access Journals (Sweden)

    Daniel O Stram

    Full Text Available Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR model that allows for a linear dose response (risk in relation to radiation and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations as if it was true dose (ignoring both shared and unshared dosimetry errors gives asymptotically unbiased estimates (i.e. the score has expectation zero and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed.

  15. Early mechanisms in radiation-induced biological damage

    International Nuclear Information System (INIS)

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical

  16. Mechanistic Effects of Calcitriol in Cancer Biology

    Directory of Open Access Journals (Sweden)

    Lorenza Díaz

    2015-06-01

    Full Text Available Besides its classical biological effects on calcium and phosphorus homeostasis, calcitriol, the active vitamin D metabolite, has a broad variety of actions including anticancer effects that are mediated either transcriptionally and/or via non-genomic pathways. In the context of cancer, calcitriol regulates the cell cycle, induces apoptosis, promotes cell differentiation and acts as anti-inflammatory factor within the tumor microenvironment. In this review, we address the different mechanisms of action involved in the antineoplastic effects of calcitriol.

  17. THz waves: biological effects, industrial and medical

    International Nuclear Information System (INIS)

    Following the debates about body scanners installed in airports for passengers security control, the non-ionizing radiations (NIR) section of the French radiation protection society (SFR) has organized a conference day to take stock of the present day knowledge about the physical aspects and the biological effects of this frequency range as well as about their medical, and industrial applications (both civil and military). This document gathers the slides of the available presentations: 1 - introduction and general considerations about THz waves, the THz physical phenomenon among NIR (J.L. Coutaz); 2 - interaction of millimeter waves with living material: from dosimetry to biological impacts (Y. Le Drean and M. Zhadobov); 3 - Tera-Hertz: standards and recommendations (B. Veyret); 4 - THz spectro-imaging technique: status and perspectives (P. Mounaix); 5 - THz technology: seeing the invisible? (J.P. Caumes); 6 - Tera-Hertz: biological and medical applications (G. Gallot); 7 - Biological applications of THz radiation: a review of events and a glance to the future (G.P. Gallerano); 8 - Industrial and military applications - liquids and solids detection in the THz domain (F. Garet); 9 - THz radiation and its civil and military applications - gas detection and quantifying (G. Mouret); 10 - Body scanners and civil aviation security (J.C. Guilpin, presentation not available). (J.S.)

  18. Dose-response relationships after incorporation of β-active radionuclides by mycobacteria

    International Nuclear Information System (INIS)

    Experimental and theoretical studies have been carried out to overcome the problems encountered in the dosimetry of the intracellular β-decay of different radionuclides in mycobacteria (BCG). The absorbed dose can be calculated theoretically if the activity is homogeneously distributed in spherical-symmetrical sections. The radiobiologic criteria determined were on the one hand the radioactivity content, and on the other hand the inactivation and the radiation-induced resistance of the bacteria to Isoniazid. On the basis of the dose-response curves the following conclusions have been drawn: The absorbed dose concept is applicable to the intracellular 3H-decay. It is the nucleus dose which determines the mutagenic effect, while inactivation is also caused by the energy deposit in the cell plasma. However, no clear correlation has been found between dose and response with regard to the local effects (transmutation, recoil energy) resulting from intracellular 35S- and 32P-decay. (orig.)

  19. The Biological Effectiveness of Four Energies of Neon Ions for the Induction of Chromosome Damage in Human Lymphocytes

    Science.gov (United States)

    George, Kerry; Hada, Megumi; Cucinotta, F. A.

    2011-01-01

    Chromosomal aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to neon ions at energies of 64, 89, 142, or 267. The corresponding LET values for these energies of neon ranged from 38-103 keV/micrometers and doses delivered were in the 10 to 80 cGy range. Chromosome exchanges were assessed in metaphase and G2 phase cells at first division after exposure using fluorescence in situ hybridization (FISH) with whole chromosome probes and dose response curves were generated for different types of chromosomal exchanges. The yields of total chromosome exchanges were similar for the 64, 89, and 142 MeV exposures, whereas the 267 MeV/u neon with LET of 38 keV/micrometers produced about half as many exchanges per unit dose. The induction of complex type chromosome exchanges (exchanges involving three or more breaks and two or more chromosomes) showed a clear LET dependence for all energies. The ratio of simple to complex type exchanges increased with LET from 18 to 51%. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The RBE(sub max) values for total chromosome exchanges for the 64 MeV/u was around 30.

  20. Microwave radiation - Biological effects and exposure standards

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, I.R.

    1980-06-01

    The thermal and nonthermal effects of exposure to microwave radiation are discussed and current standards for microwave exposure are examined in light of the proposed use of microwave power transmission from solar power satellites. Effects considered include cataractogenesis at levels above 100 mW/sq cm, and possible reversible disturbances such as headaches, sleeplessness, irritability, fatigue, memory loss, cardiovascular changes and circadian rhythm disturbances at levels less than 10 mW/sq cm. It is pointed out that while the United States and western Europe have adopted exposure standards of 10 mW/sq cm, those adopted in other countries are up to three orders of magnitude more restrictive, as they are based on different principles applied in determining safe limits. Various aspects of the biological effects of microwave transmissions from space are considered in the areas of the protection of personnel working in the vicinity of the rectenna, interactions of the transmitted radiation with cardiac pacemakers, and effects on birds. It is concluded that thresholds for biological effects from short-term microwave radiation are well above the maximal power density of 1 mW/sq cm projected at or beyond the area of exclusion of a rectenna.

  1. Superlinear dose response of thermoluminescence (TL) and optically stimulated luminescence (OSL) signals in luminescence materials: An analytical approach

    Energy Technology Data Exchange (ETDEWEB)

    Pagonis, Vasilis, E-mail: vpagonis@mcdaniel.edu [Physics Department, McDaniel College, Westminster, MD 21158 (United States); Chen, Reuven [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel); Lawless, John L. [Redwood Scientific Incorporated, Pacifica, CA 94044-4300 (United States)

    2012-06-15

    The phenomenon of superlinear dose response of thermoluminescence (TL) and optically stimulated luminescence (OSL) signals has been reported for several important dosimetric materials. We develop new analytical equations for the filling of traps and centers during irradiation and for the read-out stage of annealed luminescence materials, within the context of a two-trap and two-center model. The equations are applicable for both TL and OSL signals in annealed dosimetric materials, and are derived under the assumptions of low irradiation doses and dominant strong retrapping (weak recombination) processes. For low doses all traps and centers display linear dose response, which leads to quadratic dose response of the integrated TL/OSL signals. A new analytical expression is presented for this well-known quadratic dose dependence, in terms of the kinetic parameters in the model. The effect of elevated irradiation temperature on the integrated TL/OSL signals is also considered, and analytical expressions are obtained for this situation as well. A new type of dose-rate effect is reported based on the modeling results, which is due to irradiation during elevated temperatures. The accuracy of the analytical expressions is verified by comparing with the results of numerical simulations. - Highlights: Black-Right-Pointing-Pointer New analytical equations for the filling of traps and centers during irradiation. Black-Right-Pointing-Pointer Equations are applicable for TL and OSL signals in annealed dosimetric materials. Black-Right-Pointing-Pointer New analytical expression for the quadratic dose dependence of TL and OSL. Black-Right-Pointing-Pointer Analytical expressions for dose response at elevated irradiation temperatures. Black-Right-Pointing-Pointer A new type of dose-rate effect is reported based on the modeling results.

  2. Biological effect of low dose radiation

    International Nuclear Information System (INIS)

    This document describes the recent findings in studies of low dose radiation effect with those by authors' group. The low dose radiation must be considered in assessment of radiation effects because it induces the biological influence unexpected hitherto; i.e., the bystander effect and genetic instability. The former is a non-targeted effect that non-irradiated cells undergo the influence of directly irradiated cells nearby, which involves cell death, chromosome aberration, micronucleus formation, mutation and carcinogenesis through cellular gap junction and/or by signal factors released. Authors' group has found the radical(s) possessing as long life time as >20 hr released from the targeted cells, a possible mediator of the effect; the generation of aneuploid cells as an early carcinogenetic change; and at dose level <10 Gy, activation of MAPK signal pathway leading to relaxation of chromatin structure. The genetic instability means the loss of stability where replication and conservation of genome are normally maintained, and is also a cause of the late radiation effect. The group has revealed that active oxygen molecules can affect the late effect like delayed cell death, giant cell formation and chromosome aberration, all of which lead to the instability, and is investigating the hypothesis that the telomere instability resulted from the abnormal post-exposure interaction with its nuclear membrane or between chromatin and nuclear matrix, is enhanced by structural distortion of nuclear genes. As well, shown is the possible suppression of carcinogenesis by p53. The group, to elucidate the mechanism underlying the low dose radiation effect, is conducting their studies in consideration of the sequential bases of physical, chemical and biological processes. (R.T.)

  3. Study on the dose-response relation of premature chromosome condensation induced by Okadaic acid

    International Nuclear Information System (INIS)

    In order to study the effect-dosage relationship between the PCC induced by Okadaic acid and the IR dosages, human peripheral blood in vitro was irradiated by X-rays at different doses (0, 0.5, 1.0, 2.0, 3.0, 5.0Gy) cultivated for 48 hours and added with Okadaic acid two hours before the end of culture. Chromosome aberrations frequencies was analyzed and compared with that induced by the conventional chromosome assay and their dose-response curves were fitted. The results show that the mitotic index of the PCC induced by Okadaic acid is higher than that of the conventional chromosome assay. And the fragment rate of chromosome condensation induced by Okadaic acid has a favorable linearity relationship with external radiation doses. (authors)

  4. Dose-response of strengthening exercise for treatment of severe neck pain in women

    DEFF Research Database (Denmark)

    Andersen, C. H.; Andersen, Lars L.; Pedersen, Mogens T.;

    2013-01-01

    Specific strength training is shown to relieve neck pain in office workers. The purpose of this study is to evaluate the effectiveness of specific strength training in women with severe neck pain and to analyze the dose-response relationship between training adherence and pain reduction. One...... hundred eighteen untrained women with severe neck pain (>30 mm VAS pain) were included from a larger study, in which the subjects were randomized to 20-week specific strength training for the neck/shoulders or to a control group. In the intention-to-treat analysis, the training group experienced greater...... better pain relief than the control group and those with low adherence (p <0.0001). The decrease from baseline in the medium and high adherence groups was 37 mm VAS (28-46 mm) and 33 mm VAS (24-43 mm), respectively. Specific strength training reduces pain intensity in women with severe neck pain, and 1...

  5. Severity of killer whale behavioral responses to ship noise: a dose-response study.

    Science.gov (United States)

    Williams, Rob; Erbe, Christine; Ashe, Erin; Beerman, Amber; Smith, Jodi

    2014-02-15

    Critical habitats of at-risk populations of northeast Pacific "resident" killer whales can be heavily trafficked by large ships, with transits occurring on average once every hour in busy shipping lanes. We modeled behavioral responses of killer whales to ship transits during 35 "natural experiments" as a dose-response function of estimated received noise levels in both broadband and audiogram-weighted terms. Interpreting effects is contingent on a subjective and seemingly arbitrary decision about severity threshold indicating a response. Subtle responses were observed around broadband received levels of 130 dB re 1 μPa (rms); more severe responses are hypothesized to occur at received levels beyond 150 dB re 1 μPa, where our study lacked data. Avoidance responses are expected to carry minor energetic costs in terms of increased energy expenditure, but future research must assess the potential for reduced prey acquisition, and potential population consequences, under these noise levels. PMID:24373666

  6. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.;

    2013-01-01

    external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of......Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we...... estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of...

  7. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

    Directory of Open Access Journals (Sweden)

    Sara C Johnston

    Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

  8. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  9. Biological Effects of Yeast β-Glucans

    Directory of Open Access Journals (Sweden)

    Vlatka Petravić-tominac

    2010-12-01

    Full Text Available β-Glucans are glucose polymers that naturally occur in yeasts, molds, algae, mushrooms, bacteria, oats and barley. Immunostimulation is one of the most important properties of β-glucans. They are classified as biological response modifiers and because of their biological activities they can be used in human and veterinary medicine and pharmacy. Additionally, β-glucans show interesting physicochemical properties and therefore could be applied in food and feed production as well as in cosmetic and chemical industries. Immunomodulation by β-glucan, both in vitro and in vivo, inhibits cancer cell growth and metastasis and prevents or reduces bacterial infection. In humans, dietary β-glucan lowers blood cholesterol, improves glucose utilization by body cells and also helps wound healing. β-Glucans work, in part, by stimulating the innate immune mechanism to fight a range of foreign challenges and could be used as an adjuvant, in combination with anti infective or antineoplastic agents, radiotherapy, and a range of topical agents and nutrients. The structure of β-glucans depends on the source they are isolated from. Native β-glucan molecules can be linked and branched in several ways. Biological properties of different β-glucan molecules are dependent on their molecular structure. Some authors claim that the β-(1→3, (1→6-glucan derived from yeast Saccharomyces cerevisiae produce the highest biological effects. Thus, in this review the β-glucans and their metabolic activity are discussed, with the special accent on those isolated from yeast. Other possible β-glucan applications, directed to cosmetic production, non-medical application in pharmaceutical and chemical industry, are also discussed.

  10. The Shape of the Dose-Response Relationship between Sugars and Caries in Adults.

    Science.gov (United States)

    Bernabé, E; Vehkalahti, M M; Sheiham, A; Lundqvist, A; Suominen, A L

    2016-02-01

    Dental caries is considered a diet-mediated disease, as sugars are essential in the caries process. However, some gaps in knowledge about the sugars-caries relationship still need addressing. This longitudinal study aimed to explore 1) the shape of the dose-response association between sugars intake and caries in adults, 2) the relative contribution of frequency and amount of sugars intake to caries levels, and 3) whether the association between sugars intake and caries varies by exposure to fluoride toothpaste. We used data from 1,702 dentate adults who participated in at least 2 of 3 surveys in Finland (Health 2000, 2004/05 Follow-up Study of Adults' Oral Health, and Health 2011). Frequency and amount of sugars intake were measured with a validated food frequency questionnaire. The DMFT index was the repeated outcome measure. Data were analyzed with fractional polynomials and linear mixed effects models. None of the 43 fractional polynomials tested provided a better fit to the data than the simpler linear model. In a mutually adjusted linear mixed effects model, the amount of, but not the frequency of, sugars intake was significantly associated with DMFT throughout the follow-up period. Furthermore, the longitudinal association between amount of sugars intake and DMFT was weaker in adults who used fluoride toothpaste daily than in those using it less often than daily. The findings of this longitudinal study among Finnish adults suggest a linear dose-response relationship between sugars and caries, with amount of intake being more important than frequency of ingestion. Also, daily use of fluoride toothpaste reduced but did not eliminate the association between amount of sugars intake and dental caries. PMID:26553884

  11. Effects of Pesticides on Biological Systems

    Directory of Open Access Journals (Sweden)

    Ergul Belge Kurutas

    2003-06-01

    Full Text Available The use of pesticid both in Turkey and other contries is widespread in order to combat against many pests which cause economical damages. However, pesticides in human pass through skin, respiratory or digestive systems and is metabolized by monooxygenase system dependent upon cytocrome P450 in liver. They also give rise to severe decreases cytochrome P450 and amount of "hem" enzyme activites of glucose-6-phosphatase, pyrophosphatase by stimulating lipid peroxidation on hepatic microsomes. In this study effects of pesticides on biological systems will be presented in genaral terms. [Archives Medical Review Journal 2003; 12(3.000: 215-228

  12. Biological effects of synchrotron radiation on crops

    Institute of Scientific and Technical Information of China (English)

    唐掌雄; 董保中; 等

    1996-01-01

    The sensitivity of germinating seeds of barley,winter wheat and spring one to synchrotron ultraviolet radiation is barley>winter wheat and spring one.But when dry seeds of the three crops are irradiated by 3.5-22keV X-rays,the sequence of their sensitivity to radiation can be changed.for irradiation of 0.6-3keV ultra soft X-rays,0.40-0.90 of the seedlings of the first generation appear mutation of striped chlorophyll defect.This biological effect has never been found for irradiation of other rays.

  13. Biological effects data: Fluoride and sulfur dioxide

    Energy Technology Data Exchange (ETDEWEB)

    McMechan, K.J. (ed.); Holton, R.L.; Ulbricht, R.J.; Morgan , J.B.

    1975-04-01

    The Alumax Pacific Aluminum Corporation has proposed construction of an aluminum reduction facility near Youngs Bay at Warrenton, Oregon. This report comprises one part of the final report to Alumax on a research project entitled, Physical, Chemical and Biological Studies of Youngs Bay.'' It presents data pertaining to the potential biological effects of fluoride and sulfur dioxide, two potentially hazardous plant-stack emissions, on selected aquatic species of the area. Companion volumes provide a description of the physical characteristics the geochemistry, and the aquatic animals present in Youngs Bay and adjacent ecosystems. An introductory volume provides general information and maps of the area, and summarizes the conclusions of all four studies. The data from the two phases of the experimental program are included in this report: lethal studies on the effects of selected levels of fluoride and sulfur dioxide on the survival rate of eleven Youngs Bay faunal species from four phyla, and sublethal studies on the effects of fluoride and sulfur dioxide on the rate of primary production of phytoplankton. 44 refs., 18 figs., 38 tabs.

  14. Dose-response relationship of neutrons and γ rays to leukemia incidence among atomic bomb survivors in Hiroshima and Nagasaki by type of leukemia, 1950--1971

    International Nuclear Information System (INIS)

    The incidence of leukemia during 1950 to 1971 in a fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki was analyzed as a function of neutron and γ kerma and marrow doses. Two dose-response models were tested for acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that the leukemia incidence depends upon the sum of separate risks imposed by γ and neutron doses. In Model I the risk from both types of radiation is assumed to be directly proportional to the respective doses, while Model II assumes that whereas the risk from neutrons is directly proportional to the dose, the risk from γ rays is proportional to dose-squared. The analysis demonstrated that the dose-response of the two types of leukemia differed by type of radiation. The data suggested that the response of acute leukemia was best explained by Model II, while the response of chronic granulocytic leukemia depended almost linearly upon neutron dose alone, because the regression coefficients associated with γ radiation for both Models I and II were not significant. The relative biological effectiveness (RBE) of neutrons in relation to γ rays for incidence of acute leukemia was estimated to be approximately 30/(Dn)/sup 1/2/ [95% confidence limits; 17/(Dn)/sup 1/2/ approx. 54/(Dn)/sup 1/2/] for kerma and 32/(Dn)/sup 1/2/ [95% confidence limits; 18/(Dn)/sup 1/2/ approx. 58/(Dn)/sup 1/2/] for marrow dose (Dn = neutron dose). If acute and chronic granulocytic leukemias are considered together as all types of leukemia, Model II appears to fit the data slightly better than Model I, but neither model is statistically rejected by the data

  15. Ionizing radiation effects on biological macromolecules

    International Nuclear Information System (INIS)

    Ionizing radiation is one of the main environmental factors for life, particularly for human beings. The primary effects of ionizing radiation produce the perturbation of biomacromolecules functionality (DNA and proteins). This effect occurs by direct action and by the indirect way of water molecules radiolysis. These primary effects result in a cascade of biochemical and biological consequences that may finally influence the general functions of the organism. In the last five decades the research activity in this field was focused on the detailed description of the effects on DNA molecules and their biochemical and biological consequences. The reason for this is the importance of the integrity of DNA for the cell life evolution, especially for the cell recovery processes or for the programmed cell death after irradiation. These aspects have main applications in very important fields as radioprotection and radiotherapy. In the present paper the mechanisms of ionizing radiation action at the molecular level will be reviewed, with focus on the protein level effects. Although comparatively a lower number of results was reported concerning the effects of ionizing radiation on the proteins, during the last years this field was reconsidered in the context of a new research trend in the field of genomics and proteomics. The structural changes which occur most often in the proteins are the breaks of chemical links, the chemical moieties ionization (for instance, the oxidation of the proteins) and the inter - protein new links (cross-linking). These changes result in a gradual loss of protein functionality, influencing particularly the ionic transport, the signal transduction across the membrane or intermolecular recognition processes of antibody-antigen type. Some studies on the ion artificial channels (as gramicidin and amphotericin) incorporated in model membranes (BLM-s or liposomes) describe structural and functional changes of the peptides after the exposure to

  16. Study of Biological Effects of Low Energy Ion Implantation on Tomato and Radish Breeding

    Institute of Scientific and Technical Information of China (English)

    LIANG Qiuxia; HUANG Qunce; CAO Gangqiang; YING Fangqing; LIU Yanbo; HUANG Wen

    2008-01-01

    Biological effects of 30 keV low energy nitrogen ion implantation on the seeds of five types of tomato and one type of radish were investigated. Results showed that low energy ions have different effects on different vegetables. The whole dose-response curve of the germination ratio did not take on "the shape of saddle", but was a rising and falling waveform with the increase or decrease in ion implantation. In the vegetable of Solanaceae, two outstanding aberrant plants were selected from M1 of Henan No.4 tomato at a dose of 7×1017 nitrogen ions/cm2, which had thin-leaves, long-petal and nipple tip fruit stably inherited to M7. Furthermore the analysis of the isozyme showed that the activity of the mutant tomato seedling was distinct in quantity and color. In Raphanus sativus L., the aberrances were obvious in the mutant of radish 791 at a dose of 5×1017 nitrogen ions/cm2, and the weight of succulent root and the volume of growth were over twice the control's. At present, many species for breeding have been identified in the field and only stable species have been selected for the experiment of production. It is evident that the low energy ion implantation technology has clear effects on vegetables' genetic improvement.

  17. Study of Biological Effects of Low Energy Ion Implantation on Tomato and Radish Breeding

    International Nuclear Information System (INIS)

    Biological effects of 30 keV low energy nitrogen ion implantation on the seeds of five types of tomato and one type of radish were investigated. Results showed that low energy ions have different effects on different vegetables. The whole dose-response curve of the germination ratio did not take on the shape of saddle, but was a rising and falling waveform with the increase or decrease in ion implantation. In the vegetable of Solanaceae, two outstanding aberrant plants were selected from M1 of Henan No.4 tomato at a dose of 7 x 1017 nitrogen ions/cm2, which had thin-leaves, long-petal and nipple tip fruit stably inherited to M7. Furthermore the analysis of the isozyme showed that the activity of the mutant tomato seedling was distinct in quantity and color. In Raphanus sativus L., the aberrances were obvious in the mutant of radish 791 at a dose of 5 x 1017 nitrogen ions/cm2, and the weight of succulent root and the volume of growth were over twice the control's. At present, many species for breeding have been identified in the field and only stable species have been selected for the experiment of production. It is evident that the low energy ion implantation technology has clear effects on vegetables' genetic improvement.

  18. Study of Biological Effects of Low Energy Ion Implantation on Tomato and Radish Breeding

    Science.gov (United States)

    Liang, Qiuxia; Huang, Qunce; Cao, Gangqiang; Ying, Fangqing; Liu, Yanbo; Huang, Wen

    2008-04-01

    Biological effects of 30 keV low energy nitrogen ion implantation on the seeds of five types of tomato and one type of radish were investigated. Results showed that low energy ions have different effects on different vegetables. The whole dose-response curve of the germination ratio did not take on "the shape of saddle", but was a rising and falling waveform with the increase or decrease in ion implantation. In the vegetable of Solanaceae, two outstanding aberrant plants were selected from M1 of Henan No.4 tomato at a dose of 7 × 1017 nitrogen ions/cm2, which had thin-leaves, long-petal and nipple tip fruit stably inherited to M7. Furthermore the analysis of the isozyme showed that the activity of the mutant tomato seedling was distinct in quantity and color. In Raphanus sativus L., the aberrances were obvious in the mutant of radish 791 at a dose of 5 × 1017 nitrogen ions/cm2, and the weight of succulent root and the volume of growth were over twice the control's. At present, many species for breeding have been identified in the field and only stable species have been selected for the experiment of production. It is evident that the low energy ion implantation technology has clear effects on vegetables' genetic improvement.

  19. Dose-response relationship for breast cancer induction at radiotherapy dose

    International Nuclear Information System (INIS)

    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. 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. 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. The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients

  20. Application of Dempster-Shafer theory in dose response outcome analysis

    Science.gov (United States)

    Chen, Wenzhou; Cui, Yunfeng; He, Yanyan; Yu, Yan; Galvin, James; Hussaini, Yousuff M.; Xiao, Ying

    2012-09-01

    The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reviews summarize the currently available three-dimensional dose/volume/outcome data from multi-institutions and numerous articles to update and refine the normal tissue dose/volume tolerance guidelines. As pointed out in the review, the data have limitations and even some inconsistency. However, with the help of new physical and statistical techniques, the information in the review could be updated so that patient care can be continually improved. The purpose of this work is to demonstrate the application of a mathematical theory, the Dempster-Shafer theory, in dose/volume/outcome data analysis. We applied this theory to the original data obtained from published clinical studies describing dose response for radiation pneumonitis. Belief and plausibility concepts were introduced for dose response evaluation. We were also able to consider the uncertainty and inconsistency of the data from these studies with Yager's combination rule, a special methodology of Dempster-Shafer theory, to fuse the data at several specific doses. The values of belief and plausibility functions were obtained at the corresponding doses. Then we applied the Lyman-Kutcher-Burman (LKB) model to fit these values and a belief-plausibility range was obtained. This range could be considered as a probability range to assist physicians and treatment planners in determining acceptable dose-volume constraints. Finally, the parameters obtained from the LKB model fitting were compared with those in Emami and Burman's papers and those from other frequentist statistics methods. We found that Emami and Burman's parameters are within the belief-plausibility range we calculated by the Dempster-Shafer theory.

  1. Application of Dempster–Shafer theory in dose response outcome analysis

    International Nuclear Information System (INIS)

    The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reviews summarize the currently available three-dimensional dose/volume/outcome data from multi-institutions and numerous articles to update and refine the normal tissue dose/volume tolerance guidelines. As pointed out in the review, the data have limitations and even some inconsistency. However, with the help of new physical and statistical techniques, the information in the review could be updated so that patient care can be continually improved. The purpose of this work is to demonstrate the application of a mathematical theory, the Dempster–Shafer theory, in dose/volume/outcome data analysis. We applied this theory to the original data obtained from published clinical studies describing dose response for radiation pneumonitis. Belief and plausibility concepts were introduced for dose response evaluation. We were also able to consider the uncertainty and inconsistency of the data from these studies with Yager's combination rule, a special methodology of Dempster–Shafer theory, to fuse the data at several specific doses. The values of belief and plausibility functions were obtained at the corresponding doses. Then we applied the Lyman–Kutcher–Burman (LKB) model to fit these values and a belief–plausibility range was obtained. This range could be considered as a probability range to assist physicians and treatment planners in determining acceptable dose–volume constraints. Finally, the parameters obtained from the LKB model fitting were compared with those in Emami and Burman's papers and those from other frequentist statistics methods. We found that Emami and Burman's parameters are within the belief–plausibility range we calculated by the Dempster–Shafer theory. (paper)

  2. 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.

  3. Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study.

    Science.gov (United States)

    Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G; Sayeed, Iqbal

    2014-02-01

    Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke. PMID:24374329

  4. RBE [relative biological effectiveness] of tritium beta radiation to gamma radiation and x-rays analyzed by both molecular and genetic methods

    International Nuclear Information System (INIS)

    The relative biological effectiveness (RBE) of tritium beta radiation to 60Co gamma radiation was determined using sex-linked recessive lethals (SLRL) induced in Drosophila melanogaster spermatozoa as the biological effect. The SLRL test, a measure of mutations induced in germ cells transmitted through successive generations, yields a linear dose-response curve in the range used in these experiments. From these ratios of the slopes of the 3H beta and the 60 Co gamma radiation linear dose response curves, an RBE of 2.7 is observed. When sources of error are considered, this observation suggests that the tritium beta particle is 2.7 ± 0.3 times more effective per unit of energy absorbed in inducing gene mutations transmitted to successive generation than 60Co gamma radiation. Ion tracks with a high density of ions (high LET) are more efficient than tracks with a low ion density (low LET) in inducing transmissible mutations, suggesting interaction among products of ionization. Molecular analysis of x-ray induced mutations shows that most mutations are deletions ranging from a few base pairs as determined from sequence data to multi locus deletions as determined from complementation tests and Southern blots. 14 refs., 1 fig

  5. The biological effects of ozone depletion.

    Science.gov (United States)

    Young, A R

    1997-05-01

    Thinning of the ozone layer is predicted to result in increased levels of ultraviolet (UV) B radiation at the earth's surface. This effect has been confirmed by measurements made in relatively unpolluted areas such as Antarctica, the southern part of South America and at mid-to-high latitudes in the northern hemisphere. It has been harder to show in populated northern latitudes because of a number of confounding factors, notably weather systems and low level ozone pollution. Although UVB forms only a small proportion of the UV spectrum it has potent biological effects so that a small increase in penetration of UVB to the earth's surface has profound effects on a wide range of life forms. Most attention has been paid to the effects of an increase in UVB on human health, particularly the effects on skin cancer, resistance to infectious diseases and cataract formation. However, the effects of increased levels of UVB on other parts of the ecosystem, particularly on the primary producers in aquatic and terrestrial food chains, may be of even. PMID:9519507

  6. Reproducibilty test of ferrous xylenol orange gel dose response with optical cone beam CT scanning

    Science.gov (United States)

    Jordan, K.; Battista, J.

    2004-01-01

    Our previous studies of ferrous xylenol orange gelatin gel have revealed a spatial dependence to the dose response of samples contained in 10 cm diameter cylinders. Dose response is defined as change in optical attenuation coefficient divided by the dose (units cm-1 Gy-1). This set of experiments was conducted to determine the reproducibility of our preparation, irradiation and full 3D optical cone beam CT scanning. The data provided an internal check of a larger storage time-dose response dependence study.

  7. Biological radiation effects of Radon in Drosophila

    International Nuclear Information System (INIS)

    In order to contribute to the knowledge on the effects of radon and its decay products, the aim of this investigation is to study the biological effects of radon using Drosophila melanogaster throught the somatic mutation and recombination test (SMART) and the analysis of some adaptative factors exposing larvaes to controlled radon atmosphers, considering that this insect could be used as biological monitor. Using the somatic mutation test a mutagenic effect was observed proportional to radon concentration, into an interval of 1 ± 0.3 to 111 ± 7.4 KBq/m3 equivalent to doses under 0.0106 Gy. The correlation analysis gives a linear (r=0.80) relationship with a positive slope of 0.2217. The same happens when gamma rays are used in the interval of 1 to 20 Gy, given a linear dose-dependent effect (r=0.878) is obtained; nevetheless the slop is smaller (m=0.003) than for radon. Analysing the results of adaptative factors of the nine exposed generations, it was found that probably radon exposition induced dominant lethals during gametogenesis or/and a selection of the more component gamets of the treated individuals in larval state. It was reflected in the significant decrease on fecundity of the generation exposed. Nevertheless the laying eggs had an increase in egg-to-adult viability and the develop velocity was higher than in control for 3 KBq/m3, this suggest that radon concentrations used were able to induce repair mechanisms. These data agree with the Hormesis hypothesis that says: low doses have positive effects on health. It was not possible to obtain a dose-effect relationship except with the develop velocity where it was found a dose-effect inverse proportion. In conclusion, Drosophila melanogaster could be a good system to obtain in vivo damaged induction concentration dependent of radon and its decay products, as well as to study the effects in an exposed population by the analysis of adaptative factors. (Author)

  8. Biological Effects of Yeast β-Glucans

    Directory of Open Access Journals (Sweden)

    Vlatka Petravić-Tominac

    2014-02-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0pt 5.4pt 0pt 5.4pt; mso-para-margin:0pt; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} β-Glucans are glucose polymers that naturally occur in yeasts, molds, algae, mushrooms, bacteria, oats and barley. Immunostimulation is one of the most important properties of β-glucans. They are classified as biological response modifiers and because of their biological activities they can be used in human and veterinary medicine and pharmacy. Additionally, β-glucans show interesting physicochemical properties and therefore could be applied in food and feed production as well as in cosmetic and chemical industries. Immunomodulation by β-glucan, both in vitro and in vivo, inhibits cancer cell growth and metastasis and prevents or reduces bacterial infection. In humans, dietary β-glucan lowers blood cholesterol, improves glucose utilization by body cells and also helps wound healing. β-Glucans work, in part, by stimulating the innate immune mechanism to fight a range of foreign challenges and could be used as an adjuvant, in combination with anti infective or antineoplastic agents, radiotherapy, and a range of topical agents and nutrients. The structure of β-glucans depends on the source they are isolated from. Native β-glucan molecules can be linked and branched in several ways. Biological properties of different β-glucan molecules are dependent on their molecular structure. Some authors claim that the β-(1→3, (1→6-glucan derived from yeast Saccharomyces cerevisiae produce the highest biological effects. Thus, in this review the β-glucans and their metabolic

  9. Biological effects of space radiation and development of effective countermeasures

    Science.gov (United States)

    Kennedy, Ann R.

    2014-04-01

    As part of a program to assess the adverse biological effects expected from astronauts' exposure to space radiation, numerous different biological effects relating to astronauts' health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronauts' vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

  10. Biological effects of progestins in breast cancer.

    Science.gov (United States)

    Pasqualini, J R; Ebert, C; Chetrite, G S

    2001-12-01

    The action of progestins is derived from many factors: structure, affinity for the progesterone receptor or for other steroid receptors, the target tissue considered, the biological response, the experimental conditions, the dose and metabolic transformation. The proliferative response to progestins in human breast cancer cells is contradictory: some progestins inhibit, others stimulate, have no effect at all, or have a dual action. For instance, medroxyprogesterone acetate has a stimulatory effect on breast cancer cells after a short period of treatment, but this effect becomes inhibitory when treatment is prolonged. It has been demonstrated that, in hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, medrogestone, promegestone) are potent sulfatase inhibitory agents. The progestins can also involve the inhibition of the mRNA expression of this enzyme. In another series of studies it was also demonstrated that some progestins are very active in inhibiting 17beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently it was observed that the progestins promegestone and medrogestone stimulate sulfotransferase for the formation of estrogen sulfates. Consequently, the action of progestins in blocking estradiol formation via sulfatase, or in stimulating the effect on sulfotransferase activity, can open interesting and new possibilities in clinical applications in breast cancer. PMID:12227886

  11. Microwave radiation: biological effects and exposure standards

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, I.R.

    1981-01-01

    The thermal effects of microwave radiation are well recognized and are discussed with particular reference to cataractogenesis; the possibility of an association cannot be questioned. Postulated nonthermal effects comprise an asthenic syndrome, and for the most part the disturbances lie within clinical norms and tolerances, and are reversible. World opinion on safe exposure levels for microwave radiation is varied, and this had led to national standards disparate by three to four orders of magnitude. The US and UK exposure standard of 10 mW/cm/sup 2/ was determined over two decades ago; the possibility of a change to a more restrictive level, in line with other countries, in the near future is examined. It is concluded that such a change, without scientific rationale, is not justified. Some biological implications of the microwave radiation from the solar power satellite are considered in terms of precautions to be taken by personnel working in the vicinity of the rectenna, effects on cardiac pacemakers, and any potential effects on birds. 14 references.

  12. Contrast media: Biologic effects and clinical application

    International Nuclear Information System (INIS)

    An overview is presented of the recent developments in contrast media and their clinical applications, plus the current state-of-the-art in computerized tomography, digital subtraction angiography, ultrasound and magnetic resonance imaging (MRI). Contents of these volumes include: an in-depth review of the historical development, modern perspectives in structure-function relationships, biologic effects on hemostats, gastrointestinal, cardiovascular systems and drug interactions. Critical and basic issues, including cellular toxicity, mutagenesis, synergism between radiation and contrast agents, mechanisms in contrast-induced reactions, and the management of such reactions in high-risk patients are also presented. Specific applications of paramagnetic compounds in MRI and the recent concept of liposome-encapsulated and particulate suspension of contrast materials in diagnostic imaging are thoroughly discussed

  13. Contrast media: Biologic effects and clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Parvez, Z.; Moncada, R.; Sovak, M.

    1987-01-01

    An overview is presented of the recent developments in contrast media and their clinical applications, plus the current state-of-the-art in computerized tomography, digital subtraction angiography, ultrasound and magnetic resonance imaging (MRI). Contents of these volumes include: an in-depth review of the historical development, modern perspectives in structure-function relationships, biologic effects on hemostats, gastrointestinal, cardiovascular systems and drug interactions. Critical and basic issues, including cellular toxicity, mutagenesis, synergism between radiation and contrast agents, mechanisms in contrast-induced reactions, and the management of such reactions in high-risk patients are also presented. Specific applications of paramagnetic compounds in MRI and the recent concept of liposome-encapsulated and particulate suspension of contrast materials in diagnostic imaging are thoroughly discussed.

  14. Dose-response relationship of γ-H2AX foci induction in human lymphocytes after X-rays exposure

    International Nuclear Information System (INIS)

    Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of γ-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and γ-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y(0.5h) = 11.66D + 0.15 (R2 = 0.99), Y(5h) = 2.44D + 0.15 (R2 = 0.99), Y(8h) = 1.57D + 0.22 (R2 = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using γ-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in γ-H2AX foci kinetics after gamma- and X-irradiation in vitro.

  15. Biological effects of deuterium - depleted water

    International Nuclear Information System (INIS)

    Deuterium-depleted water (DDW) is represented by water that has an isotopic content smaller than 145 ppm D/(D + H). DDW production technique consists in the separation of deuterium from water by a continuous distillation process under pressure of about 133.3 mbar. The water used as raw material has a isotopic content of 145 ppm D/(D + H) and can be demineralized water, distillated water or condensed-steam. DDW results as a distillate with an isotopic deuterium content of 15-80 ppm, depending on the level we want to achieve. Beginning with 1996 the Institute of Cryogenics and Isotopic Technologies, DDW producer, co-operated with Romanian specialized institutes for studying the biological effects of DDW. The role of naturally occurring D in living organisms was examined by using DDW instead of natural water. These investigations led to the following conclusions: - DDW caused a tendency towards the increase of the basal tone, accompanied by the intensification of the vasoconstrictor effects of phenylefrine, noradrenaline and angiotensin; the increase of the basal tone and vascular reactivity produced by the DDW persists after the removal of the vascular endothelium; - Animals treated with DDW showed an increase of the resistance both to sublethal and lethal gamma radiation doses, suggesting a radioprotective action by the stimulation of non-specific immune defense mechanisms; - DDW stimulates immuno-defense reactions represented by the opsonic, bactericidal and phagocyte capacity of the immune system together with an increase in the number of poly-morphonuclear neutrophils; - Investigations regarding artificial reproduction of fish with DDW fecundated solutions confirmed favorable influence in embryo growth stage and resistance and following growth stages; - It was studied germination, growth and quantitative character variability in plants; one can remark the favorable influence of DDW on biological processes in plants in various ontogenetic stages. (authors)

  16. Food irradiation and its biological effects

    International Nuclear Information System (INIS)

    Irradiation of foods drew attention mostly in 1960s for disinfestation of food grains, spices and sprout inhibition in mainly potato and onion. γ-irradiation at 0.25 to 1 kGy dosage levels are usually used for irradiating grains, legumes, spices and sprout-prone vegetables. Irradiation of foods with in permissible dosage levels of 0.25 to 5 kGy is usually considered fairly safe from human consumption point of view not withstanding usual health concerns about its usage in foods. Irradiation of foods, in mostly solid or semi-solid form, at 5 kGy levels of γ-irradiation can achieve radicidation or, radiation equivalent of pasteurization and, if γ-irradiation is used at 10 kGy, it can achieve radappertization or, radiation equivalent of thermal commercial sterilization. However, the food industry uses γ-irradiation at 0.25 to 2 kGy only for mostly disinfestation of food grains/legumes, spices, sprout inhibition in potato and onion and, for surface sanitation of frozen fish, poultry and meat. Exposure to irradiation creates free radicals in foods that are capable of destroying some of the spoilage and pathogenic microflora but the same can also damage vitamins and enzymes besides creating some new harmful new chemical species, called unique radiolytic products (URPs), by combining with certain chemicals that a food may be laced with (like pesticides/fungicides). Exposure to high-energy electron beams are also known to create deleterious biological effects which may even lead to detection of trace amounts of radioactivity in the food. Some possible causes delineated for such harmful biological effects of irradiation include: irradiation induced vitamin deficiencies, the inactivity of enzymes in the foods, DNA damage and toxic radiolytic products in the foods. Irradiation, a non-thermal food preservation technique, has a role in salvaging enormous post harvest losses (25-30%) in developing economies to increase the per capita availability of foods. (author)

  17. PCBS: CANCER DOSE-RESPONSE ASSESSMENT AND APPLICATION TO ENVIRONMENTAL MIXTURES (1996)

    Science.gov (United States)

    This report updates the cancer dose-response assessment for polychlorinated biphenyls (PCBs) and shows how information on toxicity, disposition, and environmental processes can be considered together to evaluate health risks from PCB mixtures in the environment. Processes that ch...

  18. Efeito dose-resposta de uma formulação de dentifrício com concentração reduzida de fluoreto: estudo in vitro Dose-response effect of a dentifrice formulation with low fluoride concentration: an in vitro study

    Directory of Open Access Journals (Sweden)

    Helena Maria Decico Negri

    2002-12-01

    Full Text Available O desenvolvimento de dentifrício com menor concentração de flúor, visando crianças menores de 6 anos, tem sido sugerido para diminuir o risco de fluorose dental. Para que um dentifrício tenha potencial anticárie é necessário que ele forme no esmalte dental flúor fracamente ligado tipo fluoreto de cálcio (CaF2, o qual é considerado o responsável pelo efeito do flúor tópico. Considerando que a formação de CaF2 é função inversa do pH, foram formulados dentifrícios com pH 5,5. Foram preparados dentifrícios com 275, 550 e 1.100 ppm , contendo NaF/sílica, para verificar efeito dose-resposta os quais foram comparados com um placebo e o dentifrício Crest® (controle positivo - padrão. A biodisponibilidade dos dentifrícios, em termos de formação de flúor total (FT, CaF2 e fluorapatita (FA no esmalte dental humano foi avaliada. Para as dosagens de íon flúor foi utilizado eletrodo específico. Os resultados mostraram que a formulação com 550 ppm de foi mais eficiente que o placebo e aquela com 275 ppm em termos de formação de CaF2 (p 0,05. Uma relação dose-efeito foi observada em termos de CaF2 formado. Os resultados sugerem que a formulação modificada contendo 550 ppm de pode ser considerada equivalente ao dentifrício padrão com 1.100 ppm, a qual seria mais segura em termos de fluorose dental.The utilization of dentifrices with low fluorine concentration, for children under 6 years of age, has been suggested to reduce the risks of dental fluorosis. However, in order to have anticariogenic potential, the dentifrice should form loosely-bound fluorine (CaF2 on dental enamel. Considering that the formation of CaF2 is a function inversely related to pH, dentifrices with pH 5.5, with 275, 550 and 1,100 ppm (NaF/silica were developed in order to assess dose-response effects. A comparison between those dentifrices, a placebo product and the Crest toothpaste (positive control - standard was carried out. Furthermore, the

  19. Biological effects of radon in Drosophila

    International Nuclear Information System (INIS)

    The main objective of this investigation, is to study the biological effects of the Radon-222 at low dose in 'Drosophila melanogaster'. It is necessary to mention that these effects will analyze from the genetic point of view for: 1) To evaluate in which form the Radon-222 to low dose it influences in some genetic components of the adaptation in Drosophila, such as: fecundity, viability egg-adult and sex proportion. 2) To evaluate which is the genetic effect that induces the Radon to low dose by means of the SMART technique in Drosophila melanogaster, and this way to try of to identify which is the possible mechanism that causes the genetic damage to somatic level. The carried out investigation was divided in three stages: 1. Tests to the vacuum resistance. 2. Test of somatic mutation, and 3. Determination of the presence of radon daughters on the adult of Drosophila. It is necessary to point out that all the experiments were made by triplicate and in each one of them was placed detectors in preset places. Those obtained results are presented inside the 4 charts included in the present work. (Author)

  20. Dose-response study of probiotic bacteria Bifidobacterium animalis subsp lactis BB-12 and Lactobacillus paracasei subsp paracasei CRL-341 in healthy young adults

    DEFF Research Database (Denmark)

    Larsen, C.N.; Nielsen, S.; Kaestel, P.;

    2006-01-01

    Objective: This study was performed to investigate the dose-response effects of supplementation with Bifidobacterium animalis subsp lactis (BB-12) and Lactobacillus paracasei subsp paracasei (CRL-431) on blood lipids, recovery from feces and bowel habits. Changes of the fecal microflora was...... analyzed in the 10(10) CFU/day probiotic and placebo group. Design: The study was designed as a randomized, placebo-controlled, double-blinded, parallel dose-response study. Subjects: Healthy young adults (18 - 40 years) were recruited by advertising in local newspapers. Of the 75 persons enrolled, 71 ( 46...

  1. Studies on the biological effects of internal exposure of alpha emitters. Carcinogenicity test of plutonium

    International Nuclear Information System (INIS)

    Outlines of carcinogenicity tests in animals given with injected or inhaled plutonium (Pu) were described. Insoluble 239PuO2 particles were nasally inhaled in rats maintained for life. The dose response relationship between incidence of their lung tumor and absorbed radiation dose in the lung revealed that>1 Gy dose increased the incidence of malignant lung tumors, which differed from findings in the U.S. probably due to the difference between particle sizes. Further, a carcinogenic mechanism specific for alpha-ray was suggested based on tumor-related gene analysis. After soluble 239Pu (citrate salt) was injected in mice, significant reduction of lifetime and early tumor- or non-tumor-death were observed when the bone dose exceeded 3 Gy. Tumors were mostly osteosarcoma, lymphoma and other soft tissue solid cancers and were different from those induced by gamma-ray, X-ray and neutron irradiation. Studies on the strain difference, on the carcinogenic mechanism and alpha-ray induced mutation and transformation are in progress, which may lead to elucidation of the biological effects of internal exposure of alpha-emitters. (K.H.)

  2. High-LET dose-response characteristics by track structure theory of heavy charged particles

    International Nuclear Information System (INIS)

    The track structure theory developed by Katz and co-workers ascribes the effect of high-LET radiation to the highly inhomogeneous dose distribution due to low energy Δ-rays ejected from the particle track. The theory predicts the effectiveness of high-LET radiation by using the ion parameters zsub(eff') effective charge of the ion, and β = v/c, the relative ion velocity, together with the characteristic dose D37 derived from low-LET dose-response characteristic of the detector and the approximate size asub(0) of the sensitive element of the detector. 60Co gamma-irradiation is used as a reference low-LET radiation, while high-LET radiation ranging from 16 MeV protons to 4 MeV/amu 160-ions covering an initial LET range of 30-5500 MeVcm2/g is obtained from a tandem Van de Graaff accelerator. A thin film (5mg/cm2) radiochromic dye cyanide plastic dosemeter was used as detector with the characteristic dose of 16.8 Mrad and a sensitive element size of 10-7 cm. Theoretical and experimental effectiveness, RBE, agreed within 10 to 25% depending on LET. (author)

  3. Dosimetry and biological effects of fast neutrons

    International Nuclear Information System (INIS)

    This thesis contains studies on two types of cellular damage: cell reproductive death and chromosome aberrations induced by irradiation with X rays, gamma rays and fast neutrons of different energies. A prerequisite for the performance of radiobiological experiments is the determination of the absorbed dose with a sufficient degree of accuracy and precision. Basic concepts of energy deposition by ionizing radiation and practical aspects of neutron dosimetry for biomedical purposes are discussed. Information on the relative neutron sensitivity of GM counters and on the effective point of measurement of ionization chambers for dosimetry of neutron and photon beams under free-in-air conditions and inside phantoms which are used to simulate the biological objects is presented. Different methods for neutron dosimetry are compared and the experimental techniques used for the investigations of cell reproductive death and chromosome aberrations induced by ionizing radiation of different qualities are presented. Dose-effect relations for induction cell inactivation and chromsome aberrations in three cultured cell lines for different radiation qualities are presented. (Auth.)

  4. Comparative study on biological effects of gamma-radiation and volatile organic compound with the plant bioassay

    International Nuclear Information System (INIS)

    This research examined the presence of hazardous materials in chemical workplace field by means of an integrated biological monitoring. 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 as sessing their effect. 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 showed a good dose-response relationship in the range of radiation applied and yielded a correlation coefficient of 0.95. On the other hand, the MCN frequency resulted in a good response to exposure time in the workplace field. In case of in situ monitoring with the Tradescantia micronucleus assay, the frequencies were 6.2± 0.5, 8.2±1.0, and 15.7± 0.8 MCN/ 100 tetrads for 2, 6, and 9 hours exposure, respectively. Inhalation of the workplace air by workers may result in chronic damage to their health as proven by micronucleus formations in Tradescantia pollen mother cells. The combination of chemical/ biological monitoring is very effective to evaluate hazardous materials in workplace field and can be alternatively used for screening hazardous materials

  5. The use of apoptosis in human lymphocytes peripheral as alternative methods in biological dosimetry of radiation effects from cobalt-60

    International Nuclear Information System (INIS)

    Gamma rays affect cells in dose-response manner, resulting in cell death, as in cancer radiotherapy. The ionizing radiation acts by transferring energy, mainly by free radicals from water radiolysis that result in nucleic acid damage and other effects in lipids and proteins, The level of exposure is indirectly estimated by physical dosimetry, but the biological dosimetry can measure the direct radiation effect, mainly in post-dividing cells by classical cytogenetic approach. Recently, it was reported that irradiated cells develop an induced programmed death or apoptosis. With a biological dosimetric technique, we measured apoptotic cell fraction in 60Co in vitro irradiated blood cells from voluntary healthy donors. The agarose gel electrophoresis showed a low sensitivity, because cell DNA presented the characteristic pattern only when the cells were exposed to 100 c Gy or more. Using a terminal DNA labeling technique we observed that the apoptotic cell fraction proportionally increases with irradiation. Similar sensitivity was observed when compared to classical cytogenetics (3 c Gy minimum detection level). These techniques are easier to perform, do not need cell culture and all cells, including interphase ones, can be analyzed, providing a good tool in biological dosimetry. (author)

  6. The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.de [Institute for nuclear chemistry, Johannes Gutenberg-University, Mainz D-55128 (Germany); Bassler, N. [Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, Aarhus C, Aarhus 8000 (Denmark); Blaickner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220 (Austria); Ziegner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220, Austria and TU Wien, Vienna University of Technology, Vienna A-1020 (Austria); Hsiao, M. C. [Insitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Liu, Y. H. [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Koivunoro, H. [Department of Physics, University of Helsinki, POB 64, FI-00014, Finland and HUS Medical Imaging Center, Helsinki University Central Hospital, FI-00029 HUS (Finland); Auterinen, I.; Serén, T.; Kotiluoto, P. [VTT Technical Research Centre of Finland, Espoo (Finland); Palmans, H. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW, United Kingdom and Medical Physics Group, EBG MedAustron GmbH, Wiener Neustadt A-2700 (Austria); Sharpe, P. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW (United Kingdom); Langguth, P. [Department of Pharmacy and Toxicology, University of Mainz, Mainz D-55128 (Germany); Hampel, G. [Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz D-55128 (Germany)

    2015-01-15

    Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The

  7. E. Biological effects of radiation on man

    International Nuclear Information System (INIS)

    This report firstly summarises information on the biological hazards of radiation and their relation to radiation dose, and hence estimates the biological risks associated with nuclear power production. Secondly, it describes the basis and present status of radiation protection standards in the nuclear power industry

  8. Inhalation of racemic epinephrine in children with asthma. Dose-response relation and comparison with salbutamol.

    Science.gov (United States)

    Kjellman, B; Tollig, H; Wettrell, G

    1980-10-01

    In this study the effects of nebulized racemic epinephrine (Micronephrine) were investigated in children with asthma. The drug was inhaled by a compressor nebulizer with a plastic mask. In the first part of the study it is shown that nebulized Micronephrine has a dose-dependent bronchodilatory effect. In the second part the effect is compared with that of nebulized salbutamol in 10 children (7-16 years of age) with bronchial asthma. The highest dose used in the dose-response trials (=0.9 mg Micronephrine/kg body-weight) was compared with 0.15 mg salbutamol/kg body-weight, which is the dose commonly used in Sweden. There was no significant difference between the drugs as regards increase of forced expiratory volume in 1 sec or duration of the increase. There was a small but significant increase in systolic blood pressure, measured 5 min after the inhalation of Micronephrine but no significant change in diastolic pressure or heart rate. Four children complained of temporary sore throat after the inhalation. PMID:7468946

  9. What Makes Biology Learning Difficult and Effective: Students' Views

    Science.gov (United States)

    Cimer, Atilla

    2012-01-01

    The present study aims to determine the biological topics that students have difficulties learning, the reasons why secondary school students have difficulties in learning biology, and ways to improve the effectiveness of students' biology learning. For these purposes, a self-administered questionnaire including three open-ended questions was…

  10. Folate intake and the risk of breast cancer: a dose-response meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Yu-Fei Zhang

    Full Text Available BACKGROUND: Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR for highest versus lowest category = 0.97; 95% CI, 0.90-1.05; P = 0.451. Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RR = 0.99; 95% CI, 0.98-1.01; P = 0.361. Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (P = 0.007 and revealed that a daily folate intake of 200-320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg. CONCLUSION/SIGNIFICANCE: Our study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer.

  11. The late biological effects of ionizing radiation

    International Nuclear Information System (INIS)

    Full text: The principal objective of the symposium was to review the current status of understanding of the late biological effects of ionizing radiation from external and internal sources. A second objective was to critically evaluate information obtained from epidemiological studies of human population groups as well as from animal experimentation in order to provide a solid scientific basis upon which problems of current concern, such as radiation protection standards and risk-benefit analysis, could be deliberated. Eighty-one papers were presented in 10 sessions which covered epidemiological studies of late effects in human populations exposed to internal and/or external ionizing radiation; quantitative and qualitative data from animal experimentation of late effects; methodological problems and modern approaches; factors influencing susceptibility or expression of late radiation injury; comparative evaluation of late effects induced by radiation and other environmental pollutants, and problems of risk assessment. In addition, there were two evening sessions for free discussion of problems of interpreting animal data, and of the epidemiological studies of occupationally exposed populations. Reports on atomic bomb survivors showed that these epidemiological studies are providing dependable data, such as dose-related excess infant mortality. The reports also revealed the need for consensus in the method employed in the interpretation of data. That was also the case with studies on occupationally exposed populations at Hanford plant, where disparate results were presented on radiation-induced neoplasia among radiation workers. These data are, however, considered not so significant in relative terms when compared to risks involved in other industries. It was recommended that national registry systems for the dosimetry and medical records of radiation workers be established and co-ordinated internationally in order to facilitate reliable epidemiological

  12. Low-Level Laser Therapy Attenuates the Myeloperoxidase Activity and Inflammatory Mediator Generation in Lung Inflammation Induced By Gut Ischemia and Reperfusion: A Dose-Response Study

    OpenAIRE

    de Lima, Flávia Mafra; Aimbire, Flávio; Miranda, Humberto; Vieira, Rodolfo Paula; de Oliveira, Ana Paula Ligeiro; Albertini, Regiane

    2014-01-01

    Introduction: Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). Herein we evaluate the dose-response effect of low-level laser therapy (LLLT) on lung inflammation induced by i-I/R.

  13. A dose-response of consuming high fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults

    Science.gov (United States)

    National Health and Nutrition Examination Survey data show increased risk of cardiovascular disease (CVD) mortality with increased intake of added sugar across quintiles. Objective: To determine the dose response effects of consuming beverages sweetened with high fructose corn syrup (HFCS) at zero, ...

  14. Dose-response and time-course of neurotoxicity and tissue concentrations of carbaryl in Brown Norway rats from preweaning to senescence.

    Science.gov (United States)

    Factors impacting sensitivity to chemicals across life stages include toxicokinetic and toxicodynamic changes. We systematically compared the dose-response (3, 7.5, 15,22.5 mg/kg) and time-course (3 or 15 mg/kg at 30, 60, 120, 240 min) of acute effects of carbaryl (oral gavage) i...

  15. Accounting for biological effectiveness in radiological protection

    International Nuclear Information System (INIS)

    Relative biological effectiveness (RBE) presents a practical problem to radiological protection when attempts are made to ensure that the assessed risks from different types of radiation and different modes of exposure to radiation are commensurate with one another. Unfortunately, the theoretical understanding of RBE is still in the stage of competing explanations and hypotheses. Furthermore, the division of the concept of dose equivalent into a set of concepts for risk assessment and another set for measurement and control has introduced conflicting requirements of a practical nature that are difficult to resolve. Many of those working in radiobiology and radiation protection have perceived the need to increase the quality factors for photon and neutron radiations. It may be more reasonable to change the quality factors for neutrons than for other radiations. The advantages and disadvantages of different methods for accommodating such changes within the dose-equivalent concepts are to be examined. The method of accommodating such a change that has the least practical disadvantages is to increase the quality factors for all secondary particles produced in tissue by neutron radiations by a constant factor. The only disadvantage would be the perception that the quality factors for these secondary particles were not treated in a consistent fashion for all types of ionising radiation. (author)

  16. 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.

  17. Computational Systems Biology and Dose Response Modeling Workshop, September 22-26, 2008

    Science.gov (United States)

    The recently published National Academy of Sciences (NAS) report “Toxicity Testing in the 21st Century” recommends a new approach to toxicity testing, based on evaluating cellular responses in a suite of toxicity pathway assays in human cells or cells lines in vitro. Such a parad...

  18. The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, F. A.

    2011-01-01

    Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, Ti-48-ions with energies ranging from 240 to 1000 MeV/u, or to Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Si beams in this study ranged from 48 to 158 keV/ m, the LET of the Ti ions ranged from 107 to 240 keV/micron, and the LET of the Fe-ions ranged from 145 to 440 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to gamma-rays. The estimates of RBEmax values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, 21.4+/-1.7 to 28.3+/-2.4 for Ti ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBEmax value for Fe ions was obtained with the 600 MeV/u beam, the highest RBEmax value for Ti ions was obtained 1000 MeV/u beam, and the highest RBEmax value for Si ions was obtained with the 170 MeV/u beam. For Si and Fe ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreasing with further increase in LET. Additional studies for low doses Si-28-ions down to 0.02 Gy will be discussed.

  19. Biologically based multistage modeling of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

    2005-08-30

    This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistage carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of

  20. 2.3.1 Biological Effects of Ionizing Radiations

    Science.gov (United States)

    Kaul, A.

    This document is part of Subvolume A 'Fundamentals and Data in Radiobiology, Radiation Biophysics, Dosimetry and Medical Radiological Protection' of Volume 7 'Medical Radiological Physics' of Landolt-Börnstein - Group VIII 'Advanced Materials and Technologies'. It contains the Subsection '2.3.1 Biological Effects of Ionizing Radiations' of the Section '2.3 Biological Effects' of the Chapter '2 Radiation and Biological Effects' with the comtents:

  1. DOSE RESPONSE OF ELASTASE-INDUCED EMPHYSEMA IN HAMSTERS

    Science.gov (United States)

    Elastase-induced emhysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. It appears that as little as 6 units of elastase produces mild emphysema in hamste...

  2. Gamma- and electron dose response of the electrical conductivity of polyaniline based polymer blends

    International Nuclear Information System (INIS)

    Complete text of publication follows. Conducting polymers, also known as 'synthetic metals' have been the subject of widespread investigations over the past decade due to their very promising characteristics. Polyaniline (PANI) holds a special position among conducting polymers in that its most highly conducting doped form can be reached by protonic acid doping or oxidative doping. It was published earlier, that the electrical conductivity of some polyaniline based polymer composites increases to a significant extent when irradiated to gamma, electron or UV radiation. The aim of the present study was to measure the high frequency conductivity of blended films of PANI with poly(vinylchloride), PVC, and chlorinated poly(propylene) irradiated in air to different doses. In order to find the most suitable composition od these composites the mass percentage of PANI within the PPCl and PVC matrix was changed between 5 - 30%. These samples were then gamma irradiated and the induced electrical conductivity was measured in the 1 kHz - 1 MHz frequency range to determine the most sensitive evaluation conditions. After selecting both the most suitable measuring conditions as well as the blend compositions the dose response of the chosen samples was determined in the dose range of 10 - 250 kGy. With respect to potential dosimetry application the effect of electron irradiation, the effect of irradiation temperature and the stability of the irradiated samples have also been investigated

  3. Dose-Response Evaluation of Braslet-M Occlusion Cuffs

    Science.gov (United States)

    Ebert, Douglas; Garcia, Kathleen; Sargsyan, Ashot E.; Ham, David; Hamilton, Douglas; Dulchavsky, Scott A.

    2010-01-01

    Introduction: Braslet-M is a set of special elasticized thigh cuffs used by the Russian space agency to reduce the effects of the head-ward fluid shift during early adaptation to microgravity by sequestering fluid in the lower extremities. Currently, no imaging modalities are used in the calibration of the device, and the pressure required to produce a predictable physiological response is unknown. This investigation intends to relate the pressure exerted by the cuffs to the extent of fluid redistribution and commensurate physiological effects. Materials and Methods: Ten healthy subjects with standardized fluid intake participated in the study. Data collection included femoral and internal jugular vein imaging in two orthogonal planes, pulsed Doppler of cervical and femoral vessels and middle cerebral artery, optic nerve imaging, and echocardiography. Braslet-M cuff pressure was monitored at the skin interface using pre-calibrated pressure sensors. Using 6 and 30 head-down tilt in two separate sessions, the effect of Braslet-M was assessed while incrementally tightening the cuffs. Cuffs were then simultaneously released to document the resulting hemodynamic change. Results: Preliminary analysis shows correlation between physical pressure exerted by the Braslet-M device and several parameters such as jugular and femoral vein cross-sections, resistivity of the lower extremity vascular bed, and others. A number of parameters reflect blood redistribution and will be used to determine the therapeutic range of the device and to prevent unsafe application. Conclusion: Braslet-M exerts a physical effect that can be measured and correlated with many changes in central and peripheral hemodynamics. Analysis of the full data set will be required to make definitive recommendations regarding the range of safe therapeutic application. Objective data and subjective responses suggest that a safer and equally effective use of Braslet can be achieved when compared with the current

  4. Evaluating dose response from flexible dose clinical trials

    Directory of Open Access Journals (Sweden)

    Baron David

    2008-01-01

    Full Text Available Abstract Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related. Methods To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5–20 mg/day, or patients with schizophrenia who received olanzapine (N = 172, 10–20 mg/day, we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses. Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect." Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

  5. Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

    Science.gov (United States)

    2014-01-01

    Introduction Although previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA. Methods Relevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis. Results We included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (Pheterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies. Conclusions Lifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years. PMID:24594022

  6. Dose-response relationships of acute exposure to sulfur dioxide

    International Nuclear Information System (INIS)

    Acute toxicity effects of sulphur dioxide are reviewed, and the derivation of a dose-lethality curve (presented as LC50 vs. time) for human exposure to sulphur dioxide is attempted for periods ranging from ten seconds to two hours. As an aid to assessment of the hazards involved in operating heavy water manufacturing facilities, the fact that sulphur dioxide would be produced by the combustion of hydrogen sulphide was briefly considered in an appendix. It is suggested that sulphuric acid, a much more toxic substance than sulphur dioxide, may also be formed in such an event. It is concluded, therefore, that an overall hazard evaluation may have to address the contributory effects of sulphuric acid. (author)

  7. SIX2 Effects on Wilms Tumor Biology

    Directory of Open Access Journals (Sweden)

    Janene Pierce

    2014-12-01

    Full Text Available Wilms tumor (WT blastema retains gene expression profiles characteristic of the multipotent nephron progenitor pool, or cap mesenchyme (CM, in the developing kidney. As a result, WT blastema and the CM are believed to represent contextual analogues of one another. Sine oculis homeobox 2 (SIX2 is a transcription factor expressed specifically in the CM, provides a critical mechanism for CM self-renewal, and remains persistently active in WT blastema, although its purpose in this childhood malignancy remains unclear. We hypothesized that SIX2, analogous to its function in development, confers a survival pathway to blastema, the putative WT stem cell. To test its functional significance in WT biology, wild-type SIX2 was overexpressed in the human WT cell line, WiT49. After validating this model, SIX2 effects on anchorage-independent growth, proliferation, invasiveness, canonical WNT pathway signaling, and gene expression of specific WNT pathway participants were evaluated. Relative to controls, WiT49 cells overexpressing SIX2 showed significantly enhanced anchorage-independent growth and early-passage proliferation representing surrogates of cell survival. Interestingly, overexpression of SIX2 generally repressed TCF/LEF-dependent canonical WNT signaling, which activates and coordinates both differentiation and stem pathways, but significantly heightened canonical WNT signaling through the survivin promoter, a mechanism that exclusively maintains the stem state. In summary, when overexpressed in a human WT cell line, SIX2 enhances cell survival and appears to shift the balance in WNT/β-catenin signaling away from a differentiation path and toward a stem cell survival path.

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

    International Nuclear Information System (INIS)

    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

  9. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    International Nuclear Information System (INIS)

    Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation

  10. Dose-response studies with ethylene dibromide. [Hydra oligactis

    Energy Technology Data Exchange (ETDEWEB)

    Adams, J.A.

    1987-04-01

    This study represents the first of a series of Descriptive-Reproductive-Toxicology Studies currently underway in the authors laboratory. Ethylene Dibromide (EDB) is suspected of causing infertility (especially in males), carcinogenesis, mutagenesis, and possibly teratogenesis. Coupling the suspected undesirable effects of EDB exposure with the fact that the chemical has broad utility (soil fumigant, fruit and grain fumigant, gasoline additive, etc.), EDB is an important agricultural and industrial toxin. In this study Hydra oligactis are exposed to EDB in an attempt to determine the acute toxicity of the chemical. Since Hydra is organized at the tissue level only, the toxin can be applied as a component of an artificial pond water (APW) medium. The EDB stock solution is 19:1 Acetone (emulsifier): EDB. Direct dilutions are made and exposures are continuous. The medium is exchanged daily after feeding. The LC50 at 48 hours incubation with EDb is 70 mgL . Compared to the LC50's for two common commercial PCB mixtures, Aroclors 1254 and 1016, EDb is shown to be a highly toxic chemical. The respective LC50's for the PCB's are 20 mgL (Aroclor 1254) and 5 mgL (Aroclor 1016) at 72 hrs. Sublethal EDB toxicity is currently being studied.

  11. Dose-response of thermoluminescence in natural kaolinite

    Energy Technology Data Exchange (ETDEWEB)

    Correcher, V., E-mail: v.correcher@ciemat.es [CIEMAT, Av. Complutense, 22, Madrid 28040 (Spain); Garcia-Guinea, J.; Crespo-Feo, E. [Museo Nacional de Ciencias Naturales, CSIC, C. Jose Gutierrez Abascal 2, Madrid 28006 (Spain); Rodriguez-Lazcano, Y. [UCM, Dpto. Fisica de Materiales. Fac. CC. Fisicas. Av. Complutense, Madrid 28040 (Spain); Prado-Herrero, P. [MICINN, Albacete 5, Madrid 28027 (Spain)

    2010-05-20

    The thermal effect on the luminescence emission of a well-characterized natural kaolinite has been investigated by means of differential thermal analysis (DTA) and thermoluminescence (TL) to determine, respectively, the modifications of the material due to the thermal treatments up to 1000 {sup o}C and its potential use in the field of dating and retrospective dosimetry. The DTA detects water loss starting at 100-120 {sup o}C, a dehydroxylation process in the range of 400-500 {sup o}C and the transformation of kaolinite into metakaolinite at 570 {sup o}C. The dose dependence of the 400 nm TL intensity of kaolinite exhibits an excellent linearity in the range of 50 mGy to 8 Gy. In addition, the stability of the induced TL signal after six months of storage shows an initial rapid decay (ca. 60%) followed by a mild slope reaching the stability longer than six months. The tests of thermal stability at different temperatures allow us to speculate in a continuum of trap distribution with progressive changes in the glow curve shape, intensity and temperature position of the maximum peak. According to this thermal behavior, some physical parameters have been estimated using the initial rise method.

  12. Dose-response relationships for female radium dial workers

    International Nuclear Information System (INIS)

    Among 1474 women employed in the United States radium dial-painting industry before 1930, there are 61 known cases of bone sarcoma and 21 cases of carcinoma of the paranasal sinuses or the mastoid air cells (''head carcinomas''). The relative effectiveness of 226Ra and 228Ra and dose-incidence relationships were examined for the 759 of these women whose radium body burden has been determined; there are 38 cases of bone sarcoma and 17 cases of head carcinoma in this group. Incidence (I) was expressed as tumor cases per person-year and the dose parameter (D) was the quantity (microcuries) of radium that entered the blood during the period of exposure. To the observed data for each type of tumor were fitted equations that can be formulated from the general form I = (C + alpha dD+ βD2)e-γ/sup D/, where C, the natural incidence for this population, was about 10-5 per person-year. For each equation, the best values of the dose coefficients were found by a least-squares fitting procedure. An equation of the form I = (C + BD2)e-/sup γD/ provided the best fit for the bone sarcomas, when the dose was expressed as microcuries of 226Ra plus 2.5 times microcuries of 228Ra. An acceptable fit to the head carcinoma data was provided by the linear equation I = C + d alpha γ with D equal to microcuries of 226Ra. As a test of bias due to selection of cases with known symptoms of malignancy, the analyses were repeated after removal of all cases for whom radium was determined only after exhumation, and no significant changes in the fitted coefficients were found. The dose-incidence equations obtained when the dose was expressed as average skeletal dose in rad are also given

  13. Dose-response curve for blood exposed to gamma-neutron mixed field by conventional cytogenetic method

    International Nuclear Information System (INIS)

    There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources 241AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)

  14. Biological effects of low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

  15. 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.

  16. Intracoronary irradiation: dose response for the prevention of restenosis in swine

    International Nuclear Information System (INIS)

    Purpose: Restenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at the site of injury. We have previously shown that high-dose radiation (20 Gy), delivered via an intracoronary 192Ir source, causes focal medial fibrosis and markedly impairs the restenosis process after balloon angioplasty in swine. This study sought to delineate the dose-response characteristics of this effect. Methods and Materials: Forty juvenile swine underwent coronary angiography; a segment of the left coronary artery was chosen as a target for balloon injury. In 30 swine, a 2 cm ribbon of 192Ir was positioned at the target segment and 20, 15, or 10 Gy were delivered to the vessel wall (10 animals/dose). Subsequently, overdilatation balloon angioplasty was performed at the irradiated segment. In 10 control swine, overdilatation balloon angioplasty was performed without previous irradiation. Thirty-eight animals survived until sacrifice at 30 ± 3 days. Histopathological analysis was performed by a pathologist in a blinded manner. The area of maximal luminal compromise within the target segment was analyzed via computer-assisted planimetry. Results: Neointimal area was decreased by 71.4% at 20 Gy and by 58.3% at 15 Gy compared with control animals (p < 0.05 for both). A stimulatory effect on smooth muscle cell proliferation was noted at 10 Gy, with a 123% increase in neointimal area compared with controls (p < 0.05). Mean percent area stenosis was also reduced by 63% at 20 Gy and by 74.8% at 15 Gy compared with controls (p < 0.05 for both). Conclusions: Intracoronary irradiation prior to overstretch balloon angioplasty markedly reduces neointima formation; this effect is dose dependent, with evidence of a significant stimulatory effect at 10 Gy. The effective therapeutic dose range for the prevention of restenosis in this model begins at approximately 15 Gy delivered to the vessel wall

  17. Biological effects of anthropogenic contaminants in the San Francisco Estuary

    Science.gov (United States)

    Thompson, B.; Adelsbach, T.; Brown, C.; Hunt, J.; Kuwabara, J.; Neale, J.; Ohlendorf, H.; Schwarzbach, S.; Spies, R.; Taberski, K.

    2007-01-01

    Concentrations of many anthropogenic contaminants in the San Francisco Estuary exist at levels that have been associated with biological effects elsewhere, so there is a potential for them to cause biological effects in the Estuary. The purpose of this paper is to summarize information about biological effects on the Estuary's plankton, benthos, fish, birds, and mammals, gathered since the early 1990s, focusing on key accomplishments. These studies have been conducted at all levels of biological organization (sub-cellular through communities), but have included only a small fraction of the organisms and contaminants of concern in the region. The studies summarized provide a body of evidence that some contaminants are causing biological impacts in some biological resources in the Estuary. However, no general patterns of effects were apparent in space and time, and no single contaminant was consistently related to effects among the biota considered. These conclusions reflect the difficulty in demonstrating biological effects due specifically to contamination because there is a wide range of sensitivity to contaminants among the Estuary's many organisms. Additionally, the spatial and temporal distribution of contamination in the Estuary is highly variable, and levels of contamination covary with other environmental factors, such as freshwater inflow or sediment-type. Federal and State regulatory agencies desire to develop biological criteria to protect the Estuary's biological resources. Future studies of biological effects in San Francisco Estuary should focus on the development of meaningful indicators of biological effects, and on key organism and contaminants of concern in long-term, multifaceted studies that include laboratory and field experiments to determine cause and effect to adequately inform management and regulatory decisions. ?? 2006 Elsevier Inc. All rights reserved.

  18. The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

    Science.gov (United States)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2012-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

  19. Studying of ion implantation effect on the biology in China

    International Nuclear Information System (INIS)

    Since low energy ion effect on the biology was observed, the ion implantation as a new mutagenic source has been widely used in improving crops and modifying microbes in China. The basic phenomenon of ion implantation effect on the biology and analytical results are reported, and the examples of its application and its further development are shown

  20. Ion irradiation and the biological effect of immune system

    International Nuclear Information System (INIS)

    Ion irradiation exists broadly in the people's life. It can induce a series of the biological effect in body depending on the different type and dose of ionization. This article expound the effect of ion irradiation on the biological function of immune system, affording the theorial guide in the appreciation, precaution and treatment of irradiation injury. (authors)

  1. Dose response and fading characteristics of an alanine-agarose gel

    International Nuclear Information System (INIS)

    The dose response of an alanine-agarose gel, analyzed by ESR spectrometry, and the stability of the radiation-induced free radicals have been investigated. The stability of the ESR signal is higher for dosimeter samples analyzed at 77 K than for dried samples, analyzed at room-temperature. The dose response is linear to within ±2% in the absorbed dose interval 2-100 Gy. The variations in spectral line shape were analyzed at temperatures between 77 and 270 K. The experimental ESR spectrum at 77 K was compared with a simulated spectrum of polycrystals of L-α-alanine. (Author)

  2. Dose-response relationship of neutron and gamma rays to chromosomally aberrant cells among atomic bomb survivors in Hiroshima and Nagasaki

    International Nuclear Information System (INIS)

    The quantitative relationship of the frequency of cells with radiation-induced chromosome aberrations in peripheral leukocytes in atomic bomb survivors has been evaluated as a function of gamma and neutron doses. Three different models have been examined; each assumes a linear or a non-linear response to gamma rays and a linear-response to neutrons. From the standpoint of the goodness of fit of these models, the model which ''best'' fits the data on the frequency of cells with radiation-induced chromosome aberrations is the exponent model, where the frequency of aberrant cells increases exponentially with dose. The goodness of fit for this model shows the frequencies of cells with any chromosome aberration or an exchange aberration to be dependent cubically on the gamma ray dose and linearly on the neutron dose. The result derived from the frequency of aberrant cells gives a conservative dose-response relationship. The relative biological effectiveness of neutrons for frequency of cells with any chromosome aberration is calculated to be 13 at 30 rad of neutrons, 6 at 100 rad, 3 at 300 rad and so on. (author)

  3. Technology Rich Biology Labs: Effects of Misconceptions.

    Science.gov (United States)

    Kuech, Robert; Zogg, Gregory; Zeeman, Stephan; Johnson, Mark

    This paper describes a study conducted on the lab sections of the general biology course for non-science majors at the University of New England, and reports findings of student misconceptions about photosynthesis and the mass/carbon uptake during plant growth. The current study placed high technology analytic tools in the hands of introductory…

  4. DNA repair processes and the shape of dose-response curves for induced genetic changes in yeast

    International Nuclear Information System (INIS)

    Gene conversion is a genetic change which requires a functional recombinational repair system. Dose-response curves for induced gene conversion in D7 strains of diploid S. cerevisiae appear to be one-hit (effect proportional to dose) for ionizing radiation or mitomycin C, but are closer to two-hit characteristics (effect proportional to square of dose) for 254 nm UV radiation or nitrous acid at sublethal doses of these agents. These data are suggest that recombinational repair in normal cells is stimulated by coincident or double-strand damage in the DNA: for example, a double-strand break produced by ionizing radiation, an interstrand cross-link produced by mitomycin C, or a double strand break produced by ''overlapping'' excision repair of two pyrimidine dimers located on opposite DNA strands within about 100 base pairs of each other. Other initiating mechanisms for UV-induced conversion may predominate when the excision repair pathway is not available (as in rad 3 mutants). It is of interest that the shapes of the dose-response curves for back mutations affecting the iIvl locus in repair - proficient D7 strains are similar to those observed for gene conversions induced by γ-rays, UV light and nitrous acid, even though the relative yields of convertants and back mutations vary considerably from one agent to another

  5. Calculating Variations in Biological Effectiveness for a 62 MeV Proton Beam.

    Science.gov (United States)

    Carante, Mario Pietro; Ballarini, Francesca

    2016-01-01

    A biophysical model of radiation-induced cell death and chromosome aberrations [called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA)] was further developed and applied to therapeutic protons. The model assumes a pivotal role of DNA cluster damage, which can lead to clonogenic cell death following three main steps: (i) a DNA "cluster lesion" (CL) produces two independent chromosome fragments; (ii) fragment mis-rejoining within a threshold distance d gives rise to chromosome aberrations; (iii) certain aberration types (dicentrics, rings, and large deletions) lead to clonogenic inactivation. The yield of CLs and the probability, f, that a chromosome fragment remains un-rejoined even if other fragment(s) are present within d, were adjustable parameters. The model, implemented as a MC code providing simulated dose-responses directly comparable with experimental data, was applied to pristine and modulated Bragg peaks of the proton beam used to treat eye melanoma at INFN-LNS in Catania, Italy. Experimental survival curves for AG01522 cells exposed to the Catania beam were reproduced, supporting the model assumptions. Furthermore, cell death and chromosome aberrations at different depths along a spread-out Bragg peak (SOBP) dose profile were predicted. Both endpoints showed an increase along the plateau, and high levels of damage were found also beyond the distal dose fall-off, due to low-energy protons. Cell death and chromosome aberrations were also predicted for V79 cells, in the same irradiation scenario as that used for AG01522 cells. In line with other studies, this work indicated that assuming a constant relative biological effectiveness (RBE) along a proton SOBP may be sub-optimal. Furthermore, it provided qualitative and quantitative evaluations of the dependence of the beam effectiveness on the considered endpoint and dose. More generally, this work represents an example of therapeutic beam characterization avoiding the use of

  6. Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

    Science.gov (United States)

    Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

    2016-07-01

    Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration. PMID:26717881

  7. Ondansetron: A newer aspect of dose response relationship on ileal smooth muscles of rabbit.

    Science.gov (United States)

    Afzal, Ayesha; Khan, Bushra Tayyaba; Bakhtiar, Salman

    2016-01-01

    There are several life threatening deadly diseases in our world but ‘Cancer’ out powers them all in recent years. Chemotherapy may be used on its own or an adjunct to other forms of therapy. Despite the advancement in cytotoxic drug therapy and supportive treatment almost 70% of patient suffer from chemotherapy induced nausea and vomiting (CINV). Ondansetron, a 5-HT(3) receptor antagonist has now become a gold standard in the treatment of chemotherapy induced nausea and vomiting. The central actions of ondansetron are well established but its peripheral actions are not well recognized. The aim of our study was to explore the peripheral actions of ondansetron. Experiments were performed in five groups (n=6) and ileal smooth muscles activity was recorded on power lab (USA). The effects of increasing concentrations of acetylcholine, serotonin & ondansetron alone was observed in first three groups. In the next two groups effects of acetylcholine and serotonin pretreated with fixed concentration (1ml) of ondansetron (10¯ϖ M)were studied. The maximum response obtained by acetylcholine served as a control for our study. Maximum response with acetylcholine was taken as 100% and with serotonin was 177 percent of control. Cumulative dose response curve with ondansetron was triphasic. At 10¯ψM it was 28.8%, whereas with 10¯ξM the amplitude decreased to 16.87%, it reached to plateau at 10¯ϖ M. Response of acetylcholine & serotonin was decreased to 57% and 78% respectively in the presence of fixed concentration of ondansetron (10¯ϖ M). Ondansetron reduces the acetylcholine and serotonin induced gastrointestinal motility. Our study has indicated that ondansetron apart from having central action also has marked peripheral actions that play an important role in CINV and may act as a partial agonist. PMID:26826825

  8. The Dose-Response Relationship of Adolescent Religious Activity and Substance Use: Variation across Demographic Groups

    Science.gov (United States)

    Steinman, Kenneth J.; Ferketich, Amy K.; Sahr, Timothy

    2008-01-01

    This article addresses two inconsistent findings in the literature on adolescent religious activity (RA) and substance use: whether a dose-response relationship characterizes the association of these variables, and whether the association varies by grade, gender, ethnicity, family structure, school type, and type of substance. Multinomial logistic…

  9. Cytogenetics dosimetry: dose-response curve for low doses of X-ray

    International Nuclear Information System (INIS)

    The purpose of this study was to conduct a preliminary study for the standardization in the future, the dose-response curve for low doses of X-rays, through the analysis of in vitro cultures of peripheral blood samples of 3 men and 3 women occupationally not exposed to artificial sources of ionizing radiation, age 18-40 years, where possible nonsmokers

  10. Dose-Response Issues Concerning the Relations between Regular Physical Activity and Health.

    Science.gov (United States)

    Rankinen, Tuomo; Bouchard, Claude

    2002-01-01

    This paper categorizes the many benefits of physical activity, offering information concerning the type of dose necessary to get that benefit. In 2000, Health Canada and the United States Centers for Disease Control and Prevention, along with other agencies, sponsored a symposium to determine whether there was a dose-response relationship between…

  11. Development of the dose-response relationship for human toxoplasma gondii infection associated with meat consumption

    Science.gov (United States)

    Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States.A substantial portion of human T. gondii infections may be acquired through the consumption of meats. The dose-response relationship for human exposure...

  12. An in vitro dynamic microcosm biofilm model for caries lesion development and antimicrobial dose-response studies.

    Science.gov (United States)

    Maske, T T; Brauner, K V; Nakanishi, L; Arthur, R A; van de Sande, F H; Cenci, M S

    2016-03-01

    Some dynamic biofilm models for dental caries development are limited as they require multiple experiments and do not allow independent biofilm growth units, making them expensive and time-consuming. This study aimed to develop and test an in vitro dynamic microcosm biofilm model for caries lesion development and for dose-response to chlorhexidine. Microcosm biofilms were grown under two different protocols from saliva on bovine enamel discs for up to 21 days. The study outcomes were as follows: the percentage of enamel surface hardness change, integrated hardness loss, and the CFU counts from the biofilms formed. The measured outcomes, mineral loss and CFU counts showed dose-response effects as a result of the treatment with chlorhexidine. Overall, the findings suggest that biofilm growth for seven days with 0.06 ml min(-1) salivary flow under exposure to 5% sucrose (3 × daily, 0.25 ml min(-1), 6 min) was suitable as a pre-clinical model for enamel demineralization and antimicrobial studies. PMID:26905384

  13. Evolutionary Tradeoffs between Economy and Effectiveness in Biological Homeostasis Systems

    OpenAIRE

    Pablo Szekely; Hila Sheftel; Avi Mayo; Uri Alon

    2013-01-01

    Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach ...

  14. Non-Thermal Effects Mobile Phones at Biological Objects

    OpenAIRE

    Ladislav Balogh

    2003-01-01

    The article deals with non-thermal effects of mobile phones on biological objects. Even though these effects are observed for longer period, there are not so far unequivocal results on obtained biological and biophysical results in this field. Biologicaleffects of electromagnetic field (EMF) depend on its character, its duration as well as on features of organism. As the receptors offield are not known (e.g. inputs of EMF into organism), its effects are judged only by non-specific reaction of...

  15. Topical Day on Biological Effects of Radiation

    International Nuclear Information System (INIS)

    The topical day has been focussed on the potential effects of ionizing radiation on human health. A general overview on molecular and biophysical aspects of radiation, its effects on cells and organisms, and the contribution of radiobiology to radiation protection and risk assessment is given. The genetic effects of radiation and its effects on the developing organism, the effects of radiation on the cell cycle and the mechanisms of radiation induced apoptosis were also discussed

  16. Topical Day on Biological Effects of Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Baatout, S.; Jacquet, P.

    1997-05-15

    The topical day has been focussed on the potential effects of ionizing radiation on human health. A general overview on molecular and biophysical aspects of radiation, its effects on cells and organisms, and the contribution of radiobiology to radiation protection and risk assessment is given. The genetic effects of radiation and its effects on the developing organism, the effects of radiation on the cell cycle and the mechanisms of radiation induced apoptosis were also discussed.

  17. SWEET CORN CULTIVAR INFLUENCES BIOLOGICALLY EFFECTIVE HERBICIDE DOSE [ABSTRACT

    Science.gov (United States)

    Competitive crop cultivars are considered a component of integrated weed management systems; however specific knowledge of interactions among crop cultivars and other management tactics, such as biologically effective herbicide dose, is limited. Observed variation in crop tolerance and weed supp...

  18. Influence of the 192Ir source decay on biological effect

    International Nuclear Information System (INIS)

    Biological effect of the 192Ir high activity source on LA795 tumor of mice and HCT-8 cells have been investigated when decay of the source power from 340.4 GBq to 81.4 GBq no marked difference was found between the two cell survival curves of HCT-8 cells and both of them compared with that of the X-ray irradiation the value of relative biological effect (0.1 survival) was 0.43. On the experiment of tumor LA795 of mice, when the source power was 293.3 GBq and 96.2 GBq, no different biological effect can be seen between the two series of figures. The relative biological effect was 0.55-0.60 (tumor growth delay) comparing with those of X-ray irradiation

  19. Biological Effects of the Great Oxidation Event

    Science.gov (United States)

    Schopf, J.

    2012-12-01

    Fossil evidence of photoautotrophy, documented in Precambrian sediments by stromatolites, stromatolitic microfossils, and carbon isotopic data consistent with autotrophic CO2-fixation, extends to ~3,500 Ma. Such data, however, are insufficient to establish the time of origin of O2-producing (cyanobacterial) photosynthesis from its anoxygenic, photosynthetic bacterial, evolutionary precursor. The oldest (Paleoarchean) stromatolites may have been formed by anoxygenic photoautotrophs, rather than the cyanobacteria that dominate Proterozoic and modern stromatolites. Unlike the cyanobacteria of Proterozoic microbial assemblages, the filamentous and coccoidal microfossils of Archean deposits may represent remnants of non-O2-producing prokaryotes. And although the chemistry of Archean organic matter shows it to be biogenic, its carbon isotopic composition is insufficient to differentiate between oxygenic and anoxygenic sources. Though it is well established that Earth's ecosystem has been based on autotrophy since its early stages and that O2-producing photosynthesis evolved earlier, perhaps much earlier, than the increase of atmospheric oxygen in the ~2,450 and ~2,320 Ma Great Oxidation Event (GOE), the time of origin of oxygenic photoautotrophy has yet to be established. Recent findings suggest that Earth's ecosystem responded more or less immediately to the GOE. The increase of atmospheric oxygen markedly affected ocean water chemistry, most notably by increasing the availability of biologically usable oxygen (which enabled the development of obligate aerobes, such as eukaryotes), and of nitrate, sulfate and hydrogen sulfide (the increase of H2S being a result of microbial reduction of sulfate), the three reactants that power the anaerobic basis of sulfur-cycling microbial sulfuretums. Fossil evidence of the earliest eukaryotes (widely accepted to date from ~1800 Ma and, arguably, ~2200 Ma) fit this scenario, but the most telling example of life's response to the GOE

  20. High-Throughput Dose-Response Measurement Using a Label-Free Microarray-in-Microplate Assay Platform.

    Science.gov (United States)

    Landry, J P; Malovichko, G; Zhu, X D

    2015-06-01

    Microarray-based binding assays facilitate the discovery of protein ligands from large collections of small molecules. Hundreds of ligands can be identified, yet only a small portion of them have interfering effects (competitive or noncompetitive) on a specific protein-receptor binding reaction. Further efficient screening of ligands for those with specific modifying effect is needed in order to take the full advantage of throughputs of microarray-based assays for drug discovery. We report a label-free "microarray-in-microplate" assay platform for simultaneous acquisition of at least 32 dose-response curves in a single experiment, each curve having 12 concentration points. When combined with ligand discovery, this makes the microarray-based platform a true high-throughout means of finding inhibitors to specific protein-receptor reactions starting from a large collection of small-molecule libraries. PMID:25921700

  1. Current research in Canada on biological effects of ionizing radiation

    International Nuclear Information System (INIS)

    A survey of current research in Canada on the biological effects of ionizing radiation has been compiled. The list of projects has been classified according to structure (organizational state of the test system) as well as according to the type of effects. Using several assumptions, ballpark estimates of expenditures on these activities have been made. Agencies funding these research activities have been tabulated and the break-down of research in government laboratories and in academic institutions has been designated. Wherever possible, comparisons have been made outlining differences or similarities that exist between the United States and Canada concerning biological radiation research. It has been concluded that relevant research in this area in Canada is inadequate. Wherever possible, strengths and weaknesses in radiation biology programs have been indicated. The most promising course for Canada to follow is to support adequately fundamental studies of the biological effects of radiation. (auth)

  2. Longitudinal evaluation of dose-response relationships for environmental exposures and pulmonary function in swine production workers.

    Science.gov (United States)

    Reynolds, S J; Donham, K J; Whitten, P; Merchant, J A; Burmeister, L F; Popendorf, W J

    1996-01-01

    Studies describing respiratory health hazards for workers in swine production facilities have been published in the United States, Sweden, Canada, the Netherlands, and Denmark. Up to 50% of these workers experience bronchitis, organic dust toxic syndrome, hyper-reactive airways disease, chronic mucous membrane irritation, and other respiratory effects. These studies clearly point to the fact that this occupational environment poses a significant health risk hazard, and that control methods are needed to protect the worker. Before precise control strategies can be developed, implemented, and evaluated, dose-response studies are required to determine acceptable target levels for exposure. A previous manuscript described the development of multiple regression equations characterizing the relationships between environmental exposures and pulmonary response in a cohort of 207 swine producers. Baseline pulmonary function was included as a significant predictor of cross-shift decrements in pulmonary function in addition to personal measurements of dust, endotoxin, and ammonia concentrations. These equations were then used to predict specific exposure levels of dust and ammonia that could be expected to elicit significant decrements in cross-shift pulmonary function. This paper presents the results from analysis of follow-up data obtained on this same cohort 2 years after the initial measurements. At the second measurement period of the study (time-2), swine workers were found to have a mean cross-shift decrease in FEV1 of 2%. Cross-shift change in FEV1 was significantly correlated with personal exposures to total dust, total endotoxin, respirable endotoxin, and ammonia. The magnitude of the decrease in FEV1 was associated with increasing airborne concentrations of these environmental parameters thus confirming the dose-response relationship observed in the initial study (time-1). The correlation of dust with FEV1 changes in workers with more than 6 years of exposure (time

  3. Aspartame tablets-gamma dose response and usability for routine radiation processing dosimetry using spectrophotometry

    International Nuclear Information System (INIS)

    Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10-4moldm-3 and xylenol orange with 2.5x10-1moldm-3 of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%

  4. Aspartame tablets-gamma dose response and usability for routine radiation processing dosimetry using spectrophotometry

    Energy Technology Data Exchange (ETDEWEB)

    Shinde, S.H. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: shs_barc@yahoo.com; Mukherjee, T. [Radiation Safety Systems Division, Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2007-02-15

    Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10{sup -4}moldm{sup -3} and xylenol orange with 2.5x10{sup -1}moldm{sup -3} of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%.

  5. Dose-response data for X-ray induced translocations in spermatogonia of rhesus monkeys

    International Nuclear Information System (INIS)

    The yields of translocations in spermatocytes after irradiation of spermatogonia of Rhesus monkeys with doses of 100, 220, or 300 rad X-rays were low and consistent with a humped dose-response curve with a peak at about 200 rad. Such a curve would agree well with earlier results on the marmoset and man, but the yields at any dose in the Rhesus monkey were lower

  6. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

  7. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    International Nuclear Information System (INIS)

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury

  8. Dose response severity functions for acoustic disturbance in cetaceans using recurrent event survival analysis

    OpenAIRE

    Harris, C. M.; Sadykova, D.; DeRuiter, S.L.; Tyack, P. L.; Miller, P.J.O.; Kvadsheim, P. H.; Lam, F.P.A.; L. Thomas

    2015-01-01

    Behavioral response studies (BRSs) aim to enhance our understanding of the behavior changes made by animals in response to specific exposure levels of different stimuli, often presented in an increasing dosage. Here, we focus on BRSs that aim to understand behavioral responses of free-ranging whales and dolphins to manmade acoustic signals (although the methods are applicable more generally). One desired outcome of these studies is dose-response functions relevant to different species, signal...

  9. Dose response curve of 60Co for premature condensed chromosome fragments of human lymphocytes

    International Nuclear Information System (INIS)

    The dose-response curves obtained by premature condensed chromosome (PCC) and conventional cellular genetic methods can be represented by two linear equations. The ratio of the slopes, KPCC/KM1, is about 28. In comparison to the conventional method, the PCC method has many advantages; e.g. it is faster, simpler, more sensitive and accurate. Its significance in the study of radiation damage is also discussed

  10. Separation of Points and Interval Estimation in Mixed Dose-Response Curves with Selective Component Labeling

    OpenAIRE

    Flake, Darl D.

    2016-01-01

    This dissertation develops, applies, and investigates new methods to improve the analysis of logistic regression mixture models. An interesting dose-response experiment was previously carried out on a mixed population, in which the class membership of only a subset of subjects (survivors) were subsequently labeled. In early analyses of the dataset, challenges with separation of points and asymmetric confidence intervals were encountered. This dissertation extends the previous analyses by char...

  11. A comparison of dose-response models for death from hematological depression

    International Nuclear Information System (INIS)

    Many radiation-induced lethality experiments that have been published for various mammalian species have been compiled into a database suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behavior within each experiment, etc. The data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Also, photon source energy, exposure geometry, and body weight considerations were used to select studies where the dose to hematopoietic marrow was nearly uniform, i.e., < +- 20%. The data base reflects 13 mammalian test species ranging from mouse to cattle. Some 211 studies were compiled but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to practical human exposures. Of the 105 studies, 70 were for various rodent species, and 35 were for nonrodent groups ranging from standard laboratory primates (body weight ∼5 kg) to cattle (body weight 375 kg). This paper considers seven different dose-response models which are tested for validity against those 105 studies. The dose-response models included: a right-skewed extreme value, a left-skewed extreme value model, log-logistic, log-probit, logistic, probit, and Weibull models. In general, the log transformed models did not improve model performance and the extreme value models did not seem consistent with the preponderance of the data. Overall, the probit and the logistic models seemed preferable over the Weibull model. 30 refs., 8 tabs

  12. ANTIOXIDANT VITAMINS AND THE RISK OF ENDOMETRIAL CANCER: A DOSE-RESPONSE META-ANALYSIS

    OpenAIRE

    Elisa V Bandera; Gifkins, Dina M.; Moore, Dirk F.; McCullough, Marjorie L; Lawrence H Kushi

    2008-01-01

    Antioxidant vitamins may reduce cancer risk by limiting oxidative DNA damage. To summarize and quantify the current epidemiologic evidence of an association between antioxidant vitamin intake and endometrial cancer we conducted a systematic literature review and meta-analysis. One cohort and 12 case-control studies presenting relevant risk estimates were identified by conducting bibliographical searches through June 2008. Dose-response meta-analyses were conducted for beta-carotene, vitamin C...

  13. On use of the multistage dose-response model for assessing laboratory animal carcinogenicity

    OpenAIRE

    Nitcheva, Daniella; Piegorsch, Walter W.; West, R. Webster

    2007-01-01

    We explore how well a statistical multistage model describes dose-response patterns in laboratory animal carcinogenicity experiments from a large database of quantal response data. The data are collected from the U.S. EPA’s publicly available IRIS data warehouse and examined statistically to determine how often higher-order values in the multistage predictor yield significant improvements in explanatory power over lower-order values. Our results suggest that the addition of a second-order par...

  14. Vitamin D dose response is underestimated by Endocrine Society's Clinical Practice Guideline

    OpenAIRE

    McKenna, Malachi J; Murray, Barbara F

    2013-01-01

    Objective The recommended daily intakes of vitamin D according to the recent Clinical Practice Guideline (CPG) of the Endocrine Society are three- to fivefold higher than the Institute of Medicine (IOM) report. We speculated that these differences could be explained by different mathematical approaches to the vitamin D dose response. Methods Studies were selected if the daily dose was ≤2000 IU/day, the duration exceeded 3 months, and 25-hydroxyvitamin D (25OHD) concentrations were measured at...

  15. Biological effects at low irradiation doses

    International Nuclear Information System (INIS)

    Full text: The best scientific evidence of radiation effects in humans initially came from epidemiological studies of atomic bomb survivors in Hiroshima and Nagasaki. While no evidence of genetic effects has been found, these studies showed a roughly linear relationship between the induction of cancer and extremely high dose-rate of atomic bomb radiation. This was consistent with the knowledge that ionizing radiation can damage DNA in linear proportion to high-dose exposures and so produces gene mutations known to be associated with cancer. In the absence of comparable low dose effects it was prudent to propose tentatively the no-threshold hypothesis (LNT) that extrapolates linearly from effects observed at very high doses to the same effects at very low doses. It was accepted by the International Commission on Radiological Protection (ICRP) and afterwards adopted by national radiation protection organizations to guide regulations for the protection of occupationally exposed workers and the public. This hypothesis that all radiation is harmful in linear proportion to the dose is the principle used for collective dose calculations of the number of deaths produced by any radiation, natural of generated, no matter how small (BEIR-2000). The National Council of Radiation Protection and Measurements Report 121, summarizes the basis for adherence to linearity of radiation health effects. Confidence in LNT at low doses is based on our understanding of the basic mechanisms involved. Genetic effects may result from a gene mutation or a chromosome aberration. The activation of a dominant acting oncogene is frequently associated with leukemia and lymphomas, while the loss of suppressor genes appears to be more frequently associated with solid tumors. It is conceptually possible, but with a vanishing small probability, that any of these effects could result from the passage of a single charged particle, causing damage to DNA that could be expressed as a mutation or small

  16. Biological effects and hazards of radiation exposure

    International Nuclear Information System (INIS)

    Radiation induced carcinogenesis and mutagenesis form the main risk to health from exposure to low levels of radiation. This risk effects can be at least qualitatively understood by considering the effects of radiation on cell DNA. Whilst exposure to high levels of radiation results in a number of identifiable effects, exposure to low levels of radiation may result in effects which only manifest themselves after many years. Risk estimates for low levels of radiation have been derived on the basis of a number of assumptions. In the case of uranium mine workers a major hazard arises from the inhalation of radon daughters. Whilst the correlation between radon daughter exposure and lung cancer incidence is well established, the numerical value of the risk factor is the subject of controversy. ICRP 50 gives a value of 10 cases per 106 person-years at risk per WLM (range 5-15 x 10-6 PYR-1 WLM-1). The effect of smoking on lung cancer incidence rates amongst miners is also controversial. Nevertheless, smoking by miners should be discouraged

  17. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    International Nuclear Information System (INIS)

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  18. A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States)

    2013-02-01

    Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  19. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States)

    2014-06-15

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  20. A comparison of dose-response models for death from hematological depression in different species

    International Nuclear Information System (INIS)

    A database has been completed suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behaviour within each experiment, etc. Data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Photon source energy, exposure geometry, and body weight considerations were used to select studies where dose to hematopoietic tissue was approximately uniform. The database reflects 13 mammalian species ranging in size from mouse to cattle. Some 211 studies were compiled, but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to human exposures. Of the 105 studies, 70 were for rodent species, 35 for non-rodent groups ranging from standard laboratory primates (body weight ∼ 5 kg) to cattle (body weight ∼ 375 kg). Seven different dose-response models are tested for validity against the 105 studies. In general, log transformation models did not improve model performance and extreme value models did not seem consistent with the preponderance of the data. Probit and the logistic models seemed preferable over the Weibull model. (author)

  1. Titanium dioxide nanoparticles – Biological effects

    OpenAIRE

    Anna Maria Świdwińska-Gajewska; Sławomir Czerczak

    2014-01-01

    Titanium dioxide occurs as particles of various sizes. Particles of up to 100 nm, corresponding to nanoparticles, and in the size range of 0.1–3 mm are the most frequently used. Titanium dioxide in a bulk form is not classified as dangerous substance, nevertheless nanoparticles may cause adverse health effects. Inhalation exposure to nano-TiO2 causes pulmonary inflammation that may lead to fibrotic and proliferative changes in the lungs. Many studies confirm the genotoxic effect of TiO2, espe...

  2. Biological Effects of Neutron and Proton Irradiations. Vol. I. Proceedings of the Symposium on Biological Effects of Neutron Irradiations

    International Nuclear Information System (INIS)

    During recent years the interest in biological effects caused by neutrons has been increasing steadily as a result of the rapid development of neutron technology and the great number of neutron sources being used. Neutrons, because of their specific physical characteristics and biological effects, form a special type of radiation hazard but, at the same time, are a prospective tool for applied radiobiology. This Symposium, held in Brookhaven at the invitation of the United States Government from 7-11 October 1963, provided an opportunity for scientists to discuss the experimental information at present available on the biological action of neutrons and to evaluate future possibilities. It was a sequel to the Symposium on Neutron Detection, Dosimetry and Standardization, which was organized by the International Atomic Energy Agency in December 1962 at Harwell. The Symposium was attended by 128 participants from 17 countries and 6 international organizations. Fifty-four papers were presented. The following subjects were discussed in various sessions: (1) Dosimetry. Estimation of absorbed dose of neutrons in biological material. (2) Biological effects of high-energy protons. (3) Cellular and genetic effects. (4) Pathology of neutron irradiation, including acute and chronic radiation syndromes (mortality, anatomical and histological changes, biochemical and metabolic disturbances) and delayed consequences. (5) Relative biological effectiveness of neutrons evaluated by different biological tests. A Panel on Biophysical Considerations in Neutron Experimentation, with special emphasis on informal discussions, was organized during the Symposium. The views of the Panel are recorded in Volume II of the Proceedings. Many reports were presented on the important subject of the relative effectiveness of the biological action of neutrons, as well as on the general pathology of neutron irradiation and the cellular and genetic effects related to it. Three survey papers considered

  3. Biological Effects of Neutron and Proton Irradiations. Vol. II. Proceedings of the Symposium on Biological Effects of Neutron Irradiations

    International Nuclear Information System (INIS)

    During recent years the interest in biological effects caused by neutrons has been increasing steadily as a result of the rapid development of neutron technology and the great number of neutron sources being used. Neutrons, because of their specific physical characteristics and biological effects, form a special type of radiation hazard but, at the same time, are a prospective tool for applied radiobiology. This Symposium, held in Brookhaven at the invitation of the United States Government from 7-11 October 1963, provided an opportunity for scientists to discuss the experimental information at present available on the biological action of neutrons and to evaluate future possibilities. It was a sequel to the Symposium on Neutron Detection, Dosimetry and Standardization, which was organized by the International Atomic Energy Agency in December 1962 at Harwell. The Symposium was attended by 128 participants from 17 countries and 6 international organizations. Fifty-four papers were presented. The following subjects were discussed in various sessions: (1) Dosimetry. Estimation of absorbed dose of neutrons in biological material. (2) Biological effects of high-energy protons. (3) Cellular and genetic effects. (4) Pathology of neutron irradiation, including acute and chronic radiation syndromes (mortality, anatomical and histological changes, biochemical and metabolic disturbances) and delayed consequences. (5) Relative biological effectiveness of neutrons evaluated by different biological tests. A Panel on Biophysical Considerations in Neutron Experimentation, with special emphasis on informal discussions, was organized during the Symposium. The views of the Panel are recorded in Volume II of the Proceedings. Many reports were presented on the important subject of the relative effectiveness of the biological action of neutrons, as well as on the general pathology of neutron irradiation and the cellular and genetic effects related to it. Three survey papers considered

  4. Relative Biological Effectiveness (RBE) of fission neutrons and gamma rays at occupational exposure levels: Volume 2, Studies on the effects of 60 equal once-weekly exposures to fission neutrons and gamma rays on survival of mice

    International Nuclear Information System (INIS)

    A total of 6316 mice were exposed to 60 once-weekly doses of 0.85 MeV fission neutrons or 60Co gamma rays and observed until they died. An additional 1404 mice were entered into the experiment and followed for part of their lifetimes; a few of these mice were lost accidentally, but most were removed for genetic testing. The mean aftersurvival (MAS) times showed dose-response curves for both neutron and gamma-ray exposures to be linear over all doses except the highest neutron dose. The relative biological effectiveness (RBE) value for neutrons, calculated as the ratio of the linear slopes of the dose-response curves for MAS times, was about 20 for both males and females. Essentially the same value was obtained by other analyses of the data. This RBE value of 20 is specific for deaths from all causes after 60 once-weekly exposures to 0.85 MeV fission neutrons, with once-weekly 60Co gamma-ray exposures as the reference radiation. The value for the RBE will probably be different for some, but not all, of the other end points (i.e., specific causes of death, especially tumors). 21 refs., 6 figs., 6 tabs

  5. Predictive modeling of nanomaterial exposure effects in biological systems

    OpenAIRE

    Liu X; Tang K.; Harper S.; Harper B; Steevens JA; Xu R

    2013-01-01

    Xiong Liu,1 Kaizhi Tang,1 Stacey Harper,2 Bryan Harper,2 Jeffery A Steevens,3 Roger Xu1 1Intelligent Automation, Inc., Rockville, MD, USA; 2Department of Environmental and Molecular Toxicology, School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USA; 3ERDC Environmental Laboratory, Vicksburg, MS, USA Background: Predictive modeling of the biological effects of nanomaterials is critical for industry and policymakers to assess the potential ha...

  6. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

    DEFF Research Database (Denmark)

    Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera;

    2010-01-01

    Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...... blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium.......Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...

  7. Dissolution and subsequent re-crystallization as zeroing mechanism, thermal properties and component resolved dose response of salt (NaCl) for retrospective dosimetry

    International Nuclear Information System (INIS)

    In the present study we report dosimetric properties of iodized salt aiming at using it as an accidental luminescent dosimeter. It was found that the very good sensitivity of its main dosimetric peak is strongly affected by thermal treatments. This is also the case for OSL emission. The sensitivity loss due to heating implies that caution should be exercised while applying single aliquot protocols for dose evaluation. The sequence of dissolution and subsequent re-crystallization was established to be an extremely effective zeroing mechanism for the TL signal. The linearity in the dose response was also monitored in the case of dissolved and subsequently re-crystallized salt. In the case of naturally occurring salt, zeroing of the TL signal due to dissolution as well as the linearity of dose response up to doses as large as 100 Gy were found to be very promising features for dating applications.

  8. Dissolution and subsequent re-crystallization as zeroing mechanism, thermal properties and component resolved dose response of salt (NaCl) for retrospective dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Polymeris, George S., E-mail: polymers@auth.gr [Faculty of Science and Arts, Physics Department, ISIK University, 34980-Sile, Istanbul (Turkey); Kitis, George [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124-Thessaloniki (Greece); Kiyak, Nafiye G. [Faculty of Science and Arts, Physics Department, ISIK University, 34980-Sile, Istanbul (Turkey); Sfamba, Ioanna; Subedi, Bhagawan [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124-Thessaloniki (Greece); Pagonis, Vasilis [Physics Department, McDaniel College, Westminster, MD 21157 (United States)

    2011-09-15

    In the present study we report dosimetric properties of iodized salt aiming at using it as an accidental luminescent dosimeter. It was found that the very good sensitivity of its main dosimetric peak is strongly affected by thermal treatments. This is also the case for OSL emission. The sensitivity loss due to heating implies that caution should be exercised while applying single aliquot protocols for dose evaluation. The sequence of dissolution and subsequent re-crystallization was established to be an extremely effective zeroing mechanism for the TL signal. The linearity in the dose response was also monitored in the case of dissolved and subsequently re-crystallized salt. In the case of naturally occurring salt, zeroing of the TL signal due to dissolution as well as the linearity of dose response up to doses as large as 100 Gy were found to be very promising features for dating applications.

  9. The radiological consequences of notional accidental releases of radioactivity from fast breeder reactors: sensitivity to the dose-effect relationships adopted for early biological effects

    International Nuclear Information System (INIS)

    This study considered the sensitivity to the dose-response relationships adopted for the estimation of early biological effects from notional accidental releases of radioactivity from fast breeder reactors. Two distinct aspects were considered: the sensitivity of the predicted consequences to variation in the dose-mortality relationships for irradiation of the bone marrow and the lung; and the influence of simple supportive medical treatment in reducing the incidence of early deaths in the exposed population. The numbers of early effects estimated in the initial study were relatively insensitive to variation in the dose-mortality relationships within the bounds proposed. The few exceptions concerned releases of particular nuclide composition, and the variation in the predicted consequences could be around an order of magnitude; the absolute numbers of effects however were in general small when the sensitivity was most pronounced. The reduction in the incidence of early deaths when using simple supportive treatment varied markedly with the nuclide composition of the release. Areas of uncertainty were identified where further research and investigation might most profitably be directed with a view to improving the reliability of the dose-effect relationships adopted and hence of the predicted consequences of the release considered. (author)

  10. Biological and therapeutical effects of Radon

    Energy Technology Data Exchange (ETDEWEB)

    Deetjen, P. [Institute of Physiologie and Balneologie, University of Innsbruck (Austria)

    1998-12-31

    In spas with a somewhat elevated Radon{sup 222} (Rn) activity (between 300 and 3000 Bq/l), the empirical medicine ended - in all parts of the world - with the same list of indications. It mainly includes the more painful rheumatic diseases such as deformation or degeneration of the joints and non bacterial inflammation of muscles, tendons or joints; Morbus Bechterew and other diseases of the vertebral column like spondylosis, spondylarthrosis or osteochondrosis. While informer times these effects were seldom documented in an objective manner, in recent years several prospective randomized double-blind studies proved the pain reducing efficacy of Radon therapy in patients with cervical pain syndromes, with chronic polyarthritis or with Morbus Bechterew. Studies in experimental animal models have accumulated remarkable data in organs, tissue and cultured cells that provide a rationale to explain the observed effects of Radon therapy in patients. (author)

  11. Biological and therapeutical effects of Radon

    International Nuclear Information System (INIS)

    In spas with a somewhat elevated Radon222 (Rn) activity (between 300 and 3000 Bq/l), the empirical medicine ended - in all parts of the world - with the same list of indications. It mainly includes the more painful rheumatic diseases such as deformation or degeneration of the joints and non bacterial inflammation of muscles, tendons or joints; Morbus Bechterew and other diseases of the vertebral column like spondylosis, spondylarthrosis or osteochondrosis. While informer times these effects were seldom documented in an objective manner, in recent years several prospective randomized double-blind studies proved the pain reducing efficacy of Radon therapy in patients with cervical pain syndromes, with chronic polyarthritis or with Morbus Bechterew. Studies in experimental animal models have accumulated remarkable data in organs, tissue and cultured cells that provide a rationale to explain the observed effects of Radon therapy in patients. (author)

  12. Biological Effects of Low Level Laser Therapy

    OpenAIRE

    Farivar, Shirin; Malekshahabi, Talieh; Shiari, Reza

    2014-01-01

    The use of low level laser to reduce pain, inflammation and edema, to promote wound, deeper tissues and nerves healing, and to prevent tissue damage has been known for almost forty years since the invention of lasers. This review will cover some of the proposed cellular mechanisms responsible for the effect of visible light on mammalian cells, including cytochrome c oxidase (with absorption peaks in the Near Infrared (NIR)). Mitochondria are thought to be a likely site for the initia...

  13. Palytoxin and Analogs: Biological and Ecological Effects

    Directory of Open Access Journals (Sweden)

    Vítor Ramos

    2010-06-01

    Full Text Available Palytoxin (PTX is a potent marine toxin that was originally found in soft corals from tropical areas of the Pacific Ocean. Soon after, its occurrence was observed in numerous other marine organisms from the same ecological region. More recently, several analogs of PTX were discovered, remarkably all from species of the dinoflagellate genus Ostreopsis. Since these dinoflagellates are also found in other tropical and even in temperate regions, the formerly unsuspected broad distribution of these toxins was revealed. Toxicological studies with these compounds shows repeatedly low LD50 values in different mammals, revealing an acute toxic effect on several organs, as demonstrated by different routes of exposure. Bioassays tested for some marine invertebrates and evidences from environmental populations exposed to the toxins also give indications of the high impact that these compounds may have on natural food webs. The recognition of its wide distribution coupled with the poisoning effects that these toxins can have on animals and especially on humans have concerned the scientific community. In this paper, we review the current knowledge on the effects of PTX and its analogs on different organisms, exposing the impact that these toxins may have in coastal ecosystems.

  14. Linking exposure to environmental pollutants with biological effects

    DEFF Research Database (Denmark)

    Sørensen, Mette; Autrup, Herman; Møller, Peter;

    2003-01-01

    Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene......, metabolism and inflammation. By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual...... setting, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time-resolved monitors for exposure to ultrafine PM and PM(2.5,) use of GPS, as well as genomics and proteomics based...

  15. Influence of Age on the Relative Biological Effectiveness of Carbon Ion Radiation for Induction of Rat Mammary Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Imaoka, Tatsuhiko, E-mail: t_imaoka@nirs.go.jp [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Nishimura, Mayumi; Daino, Kazuhiro [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Kokubo, Toshiaki [Department of Technical Support and Development, Research Development and Support Center, National Institute of Radiological Sciences, Chiba (Japan); Doi, Kazutaka [Regulatory Sciences Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Iizuka, Daisuke [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima (Japan); Nishimura, Yukiko [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Okutani, Tomomi [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Department of Biology, Graduate School of Science, Chiba University, Chiba (Japan); Takabatake, Masaru [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan); Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo (Japan); Kakinuma, Shizuko; Shimada, Yoshiya [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba (Japan)

    2013-03-15

    Purpose: The risk of developing secondary cancer after radiotherapy, especially after treatment of childhood cancers, remains a matter of concern. The high biological effects of carbon-ion radiation have enabled powerful radiotherapy, yet the approach is commonly restricted to the treatment of adults. Susceptibility of the fetus to particle radiation–induced cancer is also unclear. The present study is aimed to investigate the effect of carbon-ion irradiation in childhood on breast carcinogenesis. Methods and Materials: We irradiated female Sprague-Dawley rats of various ages (embryonic days 3, 13, and 17 and 1, 3, 7, and 15 weeks after birth) with {sup 137}Cs γ rays or a 290-MeV/u monoenergetic carbonion beam (linear energy transfer, 13 keV/μm). All animals were screened weekly for mammary carcinoma by palpation until they were 90 weeks old. Results: Irradiation of fetal and mature (15-week-old) rats with either radiation source at a dose of 0.2 or 1 Gy did not substantially increase the hazard ratio compared with the nonirradiated group. Dose responses (0.2-2.0 Gy) to γ rays were similar among the groups of rats irradiated 1, 3, and 7 weeks after birth. The effect of carbon ions increased along with the age at the time of irradiation, indicating relative biological effectiveness values of 0.2 (−0.3, 0.7), 1.3 (1.0, 1.6), and 2.8 (1.8, 3.9) (mean and 95% confidence interval) for animals that were 1, 3, and 7 weeks of age, respectively. Conclusions: Our findings imply that carbonion therapy may be associated with a risk of secondary breast cancer in humans, the extent of which may depend on the age of the patient at the time of irradiation.

  16. Influence of Age on the Relative Biological Effectiveness of Carbon Ion Radiation for Induction of Rat Mammary Carcinoma

    International Nuclear Information System (INIS)

    Purpose: The risk of developing secondary cancer after radiotherapy, especially after treatment of childhood cancers, remains a matter of concern. The high biological effects of carbon-ion radiation have enabled powerful radiotherapy, yet the approach is commonly restricted to the treatment of adults. Susceptibility of the fetus to particle radiation–induced cancer is also unclear. The present study is aimed to investigate the effect of carbon-ion irradiation in childhood on breast carcinogenesis. Methods and Materials: We irradiated female Sprague-Dawley rats of various ages (embryonic days 3, 13, and 17 and 1, 3, 7, and 15 weeks after birth) with 137Cs γ rays or a 290-MeV/u monoenergetic carbonion beam (linear energy transfer, 13 keV/μm). All animals were screened weekly for mammary carcinoma by palpation until they were 90 weeks old. Results: Irradiation of fetal and mature (15-week-old) rats with either radiation source at a dose of 0.2 or 1 Gy did not substantially increase the hazard ratio compared with the nonirradiated group. Dose responses (0.2-2.0 Gy) to γ rays were similar among the groups of rats irradiated 1, 3, and 7 weeks after birth. The effect of carbon ions increased along with the age at the time of irradiation, indicating relative biological effectiveness values of 0.2 (−0.3, 0.7), 1.3 (1.0, 1.6), and 2.8 (1.8, 3.9) (mean and 95% confidence interval) for animals that were 1, 3, and 7 weeks of age, respectively. Conclusions: Our findings imply that carbonion therapy may be associated with a risk of secondary breast cancer in humans, the extent of which may depend on the age of the patient at the time of irradiation

  17. Dose response of selected solid state detectors in applied homogeneous transverse and longitudinal magnetic fields

    International Nuclear Information System (INIS)

    Purpose: MR-Linac devices under development worldwide will require standard calibration, commissioning, and quality assurance. Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is therefore evaluated in varying transverse and longitudinal magnetic fields for this purpose. Methods: The Monte Carlo code PENELOPE was used to model irradiation of a PTW 60003 diamond detector and IBA PFD diode detector in the presence of a magnetic field. The field itself was varied in strength, and oriented both transversely and longitudinally with respect to the incident photon beam. The long axis of the detectors was oriented either parallel or perpendicular to the photon beam. The dose to the active volume of each detector in air was scored, and its ratio to dose with zero magnetic field strength was determined as the “dose response” in magnetic field. Measurements at low fields for both detectors in transverse magnetic fields were taken to evaluate the accuracy of the simulations. Additional simulations were performed in a water phantom to obtain few representative points for beam profile and percent depth dose measurements. Results: Simulations show significant dose response as a function of magnetic field in transverse field geometries. This response can be near 20% at 1.5 T, and it is highly dependent on the detectors’ relative orientation to the magnetic field, the energy of the photon beam, and detector composition. Measurements at low transverse magnetic fields verify the simulations for both detectors in their relative orientations to radiation beam. Longitudinal magnetic fields, in contrast, show little dose response, rising slowly with magnetic field, and reaching 0.5%–1% at 1.5 T regardless of detector orientation. Water tank and in air simulation results were the same within simulation uncertainty where lateral electronic equilibrium is present and expectedly

  18. Dose-rate effect on chromosomal aberrations induced by 60Co γ-rays irradiation in human peripheral blood lymphocyte

    International Nuclear Information System (INIS)

    To estimate exactly the biological dose of persons exposed to different dose rate, human peripheral blood was exposed to 60Co γ-rays in vitro at low, middle and high dose rates respectively and chromosome samples were prepared, then dose-response curves were established according to the dicentrics and ring frequencies. The result showed that the aberration frequency at same dose level increased with dose rate and there was an obvious dose-rate effect. Absorbed dose estimated with low dose-rate dose-response curve was higher markedly than that with high dose-rate dose-response curve. So, considering the effect of dose-rate, approximate dose-rate dose-response curve should be chosen when absorbed dose estimation and the result will be credible. (authors)

  19. Biological effects of fruit and vegetables

    DEFF Research Database (Denmark)

    Dragsted, L. O.; Krath, B.; Ravn-Haren, Gitte;

    2006-01-01

    A strong and persistent effect of plant-derived foods on the prevention of lifestyle diseases has emerged from observational studies. Several groups of constituents in plants have been identified as potentially health promoting in animal studies, including cholesterol-lowering factors, antioxidants......-cholesterol, but does not affect sex hormones. In conclusion, it has been shown that total cholesterol and LDL-cholesterol, markers of peripheral lipid oxidation, and erythrocyte GPX1 activity are affected by high intakes of fruit and vegetables. This finding provides support for a protective role of dietary fruit...

  20. Nanosilver – Harmful effects of biological activity

    Directory of Open Access Journals (Sweden)

    Anna Maria Świdwińska-Gajewska

    2014-12-01

    Full Text Available Nanosilver, also identified as colloidal silver, has been known and used for ages to combat diseases or prolong food freshness. It usually occurs in the form of a suspension consisting of particles of size < 100 nm. Due to its specific properties, silver nanoparticles are used in many technologies to produce medical devices, textiles, conductive materials or photovoltaic cells. The growing popularity of nanosilver applications increases the number of people occupationally exposed to this substance. Potential exposure routes for silver nanoparticles are through dermal, oral and inhalation pathways. Silver nanoparticles may be absorbed through the lungs, intestine, and through the skin into circulation and thus may reach such organs as the liver, kidney, spleen, brain, heart and testes. Nanosilver may cause mild eyes and skin irritations. It can also act as a mild skin allergen. Inhalation of silver nanoparticles mainly affects the lungs and liver. It has been demonstrated that silver nanoparticles may be genotoxic to mammalian cells. There are some alarming reports on the adverse effects of silver nanoparticles on reproduction of experimental animals. Exposure to silver nanoparticles may exert a neurotoxic effect and affect cognitive functions, causing the impairment of short-term and working memory. Maximum admissible concentration (MAC for the inhalable fraction of silver of 0.05 mg/m3 is currently binding in Poland. In light of toxicological studies of silver nanoparticles it seems reasonable to update the hygiene standards for silver with nanoparticles as a separate fraction. Med Pr 2014;65(6:831–845

  1. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA. PMID

  2. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    International Nuclear Information System (INIS)

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF

  3. Enhancements in biologically effective ultraviolet radiation following volcanic eruptions

    Science.gov (United States)

    Vogelmann, A. M.; Ackerman, T. P.; Turco, R. P.

    1992-01-01

    A radiative transfer model is used to estimate the changes in biologically effective radiation (UV-BE) at the earth's surface produced by the El Chichon (1982) and Mount Pinatubo (1991) eruptions. It is found that in both cases surface intensity can increase because the effect of ozone depletion outweighs the increased scattering.

  4. Effects of saltcedar invasion and biological control on small mammals

    Science.gov (United States)

    Effects of invasive saltcedars (Tamarix spp.) on bird populations and communities have received considerable interest, but impacts on other vertebrate taxa have received less attention. Moreover, only one published study examined effects on vertebrates of biological control efforts directed at saltc...

  5. Electromagnetic field induced biological effects in humans.

    Science.gov (United States)

    Kaszuba-Zwolińska, Jolanta; Gremba, Jerzy; Gałdzińska-Calik, Barbara; Wójcik-Piotrowicz, Karolina; Thor, Piotr J

    2015-01-01

    Exposure to artificial radio frequency electromagnetic fields (EMFs) has increased significantly in recent decades. Therefore, there is a growing scientific and social interest in its influence on health, even upon exposure significantly below the applicable standards. The intensity of electromagnetic radiation in human environment is increasing and currently reaches astronomical levels that had never before experienced on our planet. The most influential process of EMF impact on living organisms, is its direct tissue penetration. The current established standards of exposure to EMFs in Poland and in the rest of the world are based on the thermal effect. It is well known that weak EMF could cause all sorts of dramatic non-thermal effects in body cells, tissues and organs. The observed symptoms are hardly to assign to other environmental factors occurring simultaneously in the human environment. Although, there are still ongoing discussions on non-thermal effects of EMF influence, on May 31, 2011--International Agency for Research on Cancer (IARC)--Agenda of World Health Organization (WHO) has classified radio electromagnetic fields, to a category 2B as potentially carcinogenic. Electromagnetic fields can be dangerous not only because of the risk of cancer, but also other health problems, including electromagnetic hypersensitivity (EHS). Electromagnetic hypersensitivity (EHS) is a phenomenon characterized by the appearance of symptoms after exposure of people to electromagnetic fields, generated by EHS is characterized as a syndrome with a broad spectrum of non-specific multiple organ symptoms including both acute and chronic inflammatory processes located mainly in the skin and nervous systems, as well as in respiratory, cardiovascular systems, and musculoskeletal system. WHO does not consider the EHS as a disease-- defined on the basis of medical diagnosis and symptoms associated with any known syndrome. The symptoms may be associated with a single source of EMF

  6. Rifaximin: An Antibiotic with Important Biologic Effects.

    Science.gov (United States)

    DuPont, H L

    2015-01-01

    Rifaximin is a poorly absorbed rifamycin drug with unique pharmacokinetic properties: bile solubility making it highly active against pathogenic and non-pathogenic bacterial flora in the bile-rich small bowel and low water solubility making it active only against highly susceptible bacteria, primarily anaerobes, in the aqueous colon. The drug has anti-inflammatory gut mucosal stabilization properties that are important to its sustained effects in non-infectious diseases. Rifaximin is used chronically or recurrently for hepatic encephalopathy and diarrhea-predominant irritable bowel syndrome. Monitoring of long-term use of rifaximin for development of resistance and then determining whether developed resistance is associated with reduced efficacy are needed. Studies of changes of intestinal flora during therapy and the health implications of these changes are also needed. PMID:26202192

  7. Biological effect of radiation on human

    International Nuclear Information System (INIS)

    1. Adaptive response when 0.01 Gy was preirradiated before high challenging dose is induced in normal cell types such normal lymphocytes, primary keratinocytes, and L929 fibroblast cells but not in neoplastic cells such as L5178Y lymphoma cells, EL-4 lymphoma cells and 308 papilloma cells. 2. Heat shock protein (HSP) 25 and inducible HSP70 is responsible for the induction of adaptive response and radioresistance - cell cycle regulation, antiapoptotic molecule and PKC activation were involved. 3. Apoptosis was induced at most 5. hrs after irradiation in primary keratinocytes, in v-rasHa transformed keratinocytes, the maximum interval was 16 hrs, and in 308 papilloma cells, the maximum was 48 hrs. 4. PKC response by radiation is correlated with induction of apoptosis. 5. Rapid induction PKCdelta in primary keratinocytes and no response of PKC epsilon may involved in radiation induced apoptosis. 6. The rate of resorption was increased when radiation was given at 2.5 days after gestation. Early death including foetal death were highly expressed when radiation was given at 7.5 days after gestation. There are no difference in incidence of late death including embryonic death. 7. 2 Gy is the most effective dose in radiation induced teratogenesis in mouse model. 8. Growth retardation and small head was present when radiation was given at 5.5, 7.5, 11.5 and 15.5 days after gestation and small head showed high incidence at 11.5 days after gestation. 9. External malformation, internal malformation and skeletal malformation was induced when radiation was given at 7.5 days after gestation. 10. OGG1-mutated cells induced radiosensitive by G2/M cell cycle arrest. 11. Radiation induced G2/M phase cell cycle and correlated with radiosensitivity. 12. PKCalpha induced differentiation. 13. Radiation exposed cells showed carcinogenic effect. 14. Organ specific radiosensitivity was shown and protein expression was involved

  8. Biological effect of radiation on human

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yun Sil; Cho, Chul Koo; Lee, Su Jae [and others

    2000-04-01

    1. Adaptive response when 0.01 Gy was preirradiated before high challenging dose is induced in normal cell types such normal lymphocytes, primary keratinocytes, and L929 fibroblast cells but not in neoplastic cells such as L5178Y lymphoma cells, EL-4 lymphoma cells and 308 papilloma cells. 2. Heat shock protein (HSP) 25 and inducible HSP70 is responsible for the induction of adaptive response and radioresistance - cell cycle regulation, antiapoptotic molecule and PKC activation were involved. 3. Apoptosis was induced at most 5. hrs after irradiation in primary keratinocytes, in v-rasHa transformed keratinocytes, the maximum interval was 16 hrs, and in 308 papilloma cells, the maximum was 48 hrs. 4. PKC response by radiation is correlated with induction of apoptosis. 5. Rapid induction PKCdelta in primary keratinocytes and no response of PKC epsilon may involved in radiation induced apoptosis. 6. The rate of resorption was increased when radiation was given at 2.5 days after gestation. Early death including foetal death were highly expressed when radiation was given at 7.5 days after gestation. There are no difference in incidence of late death including embryonic death. 7. 2 Gy is the most effective dose in radiation induced teratogenesis in mouse model. 8. Growth retardation and small head was present when radiation was given at 5.5, 7.5, 11.5 and 15.5 days after gestation and small head showed high incidence at 11.5 days after gestation. 9. External malformation, internal malformation and skeletal malformation was induced when radiation was given at 7.5 days after gestation. 10. OGG1-mutated cells induced radiosensitive by G2/M cell cycle arrest. 11. Radiation induced G2/M phase cell cycle and correlated with radiosensitivity. 12. PKCalpha induced differentiation. 13. Radiation exposed cells showed carcinogenic effect. 14. Organ specific radiosensitivity was shown and protein expression was involved.

  9. Dose-response evaluation after Yttrium-90 resin microsphere radio-embolization of breast cancer liver metastases

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: Yttrium-90 resin microsphere radio-embolization is a valuable therapeutic option in metastatic breast cancer patients with progressive disease refractory to chemotherapy. The goal of this study was to evaluate the dose-response relationship of liver metastasis based on a 3D voxelized 90Y PET dosimetry. Materials and methods: we studied the dose-response relationship of twelve hepatic lesions in four selected patients with metastatic breast cancer who underwent 90Y radio-embolization (Sirtex SIR-Spheres Pty Ltd.). The administered activity ranged from 1 to 1.3 GBq. Ten days before treatment, patients underwent a baseline 18F-FDG PET/CT. The determination of the 90Y-microsphere activity to administer for treatment was based on the BSA method refined with the partition model derived from a 99mTc-MAA SPECT/CT performed a week prior to radio-embolization. Within 24 hours after treatment, 90Y TOF PET/CT imaging was performed. A follow-up 18F-FDG PET/CT was performed 1 month after the treatment to evaluate the response to radio-embolization. For each patient, 3D voxelized dose-maps were obtained from the post-treatment 90Y TOF PET/CT. A volume of interest (VOI) was drawn for each selected hepatic lesion using the baseline 18F-FDG PET/CT. To obtain dose-volume histogram (DVH) for each lesion, image co-registration and VOI masks were generated using the PMOD 3.4 software and then exported in Matlab for dose calculation. Furthermore, the average absorbed dose in lesions was corrected for PVE effects by multiplication for appropriate (phantom-based) recovery coefficients according to the lesion size. Early metabolic lesion response was assessed in terms of variation in the maximum standard uptake value (ΔSUVmax) between baseline and follow-up 18F-FDG PET/CT. The average absorbed dose for each lesion was associated with the respective metabolic response. Results: for the 12 selected lesions, the average volume was 35 cm3 (range 8-147 cm3

  10. Comment on the treatment of dose-response relationship for the epidemiological data of atomic bomb survivors

    International Nuclear Information System (INIS)

    As for the dose-response relationship for solid cancer incidence rate at low dose radiation, the epidemiological study of atomic bomb survivors by RERF have been regarded to be the most important and authentic, and ICRP has its conceptual basis in the policy of radiation protection on this data for adopting the linear, non-threshold (LNT) model. However, we have found that there are two fundamental problems in the way of treatment of the data, and we believe it may bring an important modification on the validity of the LNT model for the interpretation of the radiation effect at low dose. The first point is that in estimating the exposure dose of the survivors, the chronic dose received by them should be considered in addition to the acute dose calculated by T65D or DS86, which only estimates the dose at the instant of explosion of the bomb. It seems there are ample evidences that the survivors received additional chronic dose due to the radioactivity contained both in the fallout and in the induced radioactivity by the neutron bombardment of the environmental materials. For example, it is a well-known fact that there was a heavy temporary shower (so to speak ''black rain'') in a wide region of the city after the bomb explosion, which contained much radioactivity due to the fission products. According to a literature, in the case of residents at Nishiyama District in Nagasaki, which is located 3 km from the explosion center but is shielded by a mountain from the instantaneous bomb explosion, the cumulative dose received by 280 residents there was estimated to be as much as 0.2 Gy, which caused an abnormal increase in the number of leukocytes for most of the residents. For the case of Hiroshima, a literature reports that the dose due to the black rain was about 0.03-0.04 Gy. In both cities, a substantial percentage of the survivors had stayed for considerable time in the contaminated area in the city after bombing, such as for the purpose of searching their families

  11. Comment on the treatment of dose-response relationship for the epidemiological data of atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Tatsuo [Radiation Education Forum, Tokyo (Japan)

    2000-05-01

    As for the dose-response relationship for solid cancer incidence rate at low dose radiation, the epidemiological study of atomic bomb survivors by RERF have been regarded to be the most important and authentic, and ICRP has its conceptual basis in the policy of radiation protection on this data for adopting the linear, non-threshold (LNT) model. However, we have found that there are two fundamental problems in the way of treatment of the data, and we believe it may bring an important modification on the validity of the LNT model for the interpretation of the radiation effect at low dose. The first point is that in estimating the exposure dose of the survivors, the chronic dose received by them should be considered in addition to the acute dose calculated by T65D or DS86, which only estimates the dose at the instant of explosion of the bomb. It seems there are ample evidences that the survivors received additional chronic dose due to the radioactivity contained both in the fallout and in the induced radioactivity by the neutron bombardment of the environmental materials. For example, it is a well-known fact that there was a heavy temporary shower (so to speak ''black rain'') in a wide region of the city after the bomb explosion, which contained much radioactivity due to the fission products. According to a literature, in the case of residents at Nishiyama District in Nagasaki, which is located 3 km from the explosion center but is shielded by a mountain from the instantaneous bomb explosion, the cumulative dose received by 280 residents there was estimated to be as much as 0.2 Gy, which caused an abnormal increase in the number of leukocytes for most of the residents. For the case of Hiroshima, a literature reports that the dose due to the black rain was about 0.03-0.04 Gy. In both cities, a substantial percentage of the survivors had stayed for considerable time in the contaminated area in the city after bombing, such as for the purpose of

  12. 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.

  13. Comparison of the dose-response relationship of radiation-induced apoptosis in the hippocampal dentate gyrus and intestinal crypt of adult mice

    International Nuclear Information System (INIS)

    The present study compared the dose-response curves for the frequency of apoptosis in mouse hippocampal dentate gyrus (DG) and intestinal crypt using whole-body gamma irradiation. The incidence of gamma-ray-induced apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labelling (TUNEL) method. TUNEL-positive apoptotic nuclei in the DG and intestinal crypt were increased in a dose-dependent pattern (0-2 Gy). The dose-response curves were linear-quadratic, with a significant relationship between the appearance of apoptosis and irradiation dose. The slopes of the dose-response curves in the DG were much steeper (∼5-6-fold) than those in the intestinal crypt within the range of 0-1 Gy exposure. Hippocampal DG might be a more effective and sensitive evaluation structure than the intestinal crypt to estimate the degree of radiation exposure in damaged organs of adult mice exposed to low irradiation dose. copy; The Author 2011. Published by Oxford Univ. Press. All rights reserved. (authors)

  14. The impact of biology on risk assessment -- Workshop of the National Research Council's board on radiation effects research. Meeting report

    International Nuclear Information System (INIS)

    The linear, nonthreshold extrapolation from a dose-response relationship for ionizing radiation derived at higher doses to doses for which regulatory standards are proposed is being challenged by some scientists and defended by others. It appears that the risks associated with exposures to doses of interest are below the risks that can be measured with epidemiologic studies. Therefore, many have looked to biology to provide information relevant to risk assessment. The workshop reported here, ''The Impact of biology on Risk Assessment,'' was planned to address the need for further information by bringing together scientists who have been working in key fields of biology and others who have been contemplating the issues associated specifically with this question. The goals of the workshop were to summarize and review the status of the relevant biology, to determine how the reported biologic data might influence risk assessment, and to identify subjects on which more data is needed

  15. Third eye, the biological effects; 3. oeil, les effets biologiques

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2004-02-01

    The discovery of a third kind of photo-receptor cell in the human eye has permitted to better understand the biological effects of lighting, not only on the vision, but also on some nervous processes, like emotion, mood, stress, biological clock, etc.. This additional dimension has led the engineers of Philips Lighting company to launch a new indoor lighting concept named 'Carpe Diem'. This concept adapts both the illuminance and the color of a lighting system according to the type of work and to the expected stimulating effect. (J.S.)

  16. Biological effect of penetration controlled irradiation with ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi; Shimizu, Takashi; Kikuchi, Masahiro; Kobayashi, Yasuhiko; Watanabe, Hiroshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Yamashita, Takao

    1997-03-01

    To investigate the effect of local irradiation with ion beams on biological systems, technique for penetration controlled irradiation has been established. The range in a target was controlled by changing the distance from beam window in the atmosphere, and could be controlled linearly up to about 31 {mu}m in biological material. In addition, the effects of the penetration controlled irradiations with 1.5 MeV/u C and He ions were examined using tobacco pollen. The increased frequency of leaky pollen produced by ion beams suggests that the efficient pollen envelope damages would be induced at the range-end of ion beams. (author)

  17. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships

    International Nuclear Information System (INIS)

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback

  18. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose volume outcome relationships

    Science.gov (United States)

    El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

    2006-11-01

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

  19. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  20. Biological isotopy. Introduction to the isotopic effects and to their applications in biology

    International Nuclear Information System (INIS)

    Since their discovery in the beginning of the 20. century, the study of stable isotopes has considerably developed. This domain, which remained limited in its applications until the 1990's, has become particularly important thereafter thanks to its practical applications and in particular to its economical impacts. Many techniques used in fraud control, in drugs use control, in selection of high-yield plants etc are based on isotopic abundance measurements. This reference book gives a synthesis of our actual knowledge on the use of stable isotopes and of isotope fractionation in biology. It presents the basic notions of isotopic biochemistry and explains the origin of the isotopic effects. The application principles of these effects to metabolism, to organisms physiology, to environmental biology etc are explained and detailed using examples and exercises. The first chapters present the basic knowledge which defines, from a mathematical point-of-view, the isotopic effects of chemical reactions or of physical processes taking place in biology. The measurements principle of natural isotopes abundance is then synthesised. Finally, all these notions are applied at different scales: enzymes, physiology, metabolism, environment, ecosystems and fraud crackdown. (J.S.)

  1. Dose-response curve of a microfluidic magnetic bead-based surface coverage sandwich assay.

    Science.gov (United States)

    Cornaglia, Matteo; Trouillon, Raphaël; Tekin, H Cumhur; Lehnert, Thomas; Gijs, Martin A M

    2015-09-25

    Magnetic micro- and nanoparticles ('magnetic beads') have been used to advantage in many microfluidic devices for sensitive antigen (Ag) detection. Today, assays that use as read-out of the signal the number count of immobilized beads on a surface for quantification of a sample's analyte concentration have been among the most sensitive and have allowed protein detection lower than the fgmL(-1) concentration range. Recently, we have proposed in this category a magnetic bead surface coverage assay (Tekin et al., 2013 [1]), in which 'large' (2.8μm) antibody (Ab)-functionalized magnetic beads captured their Ag from a serum and these Ag-carrying beads were subsequently exposed to a surface pattern of fixed 'small' (1.0μm) Ab-coated magnetic beads. When the system was exposed to a magnetic induction field, the magnet dipole attractive interactions between the two bead types were used as a handle to approach both bead surfaces and assist with Ag-Ab immunocomplex formation, while unspecific binding (in absence of an Ag) of a large bead was reduced by exploiting viscous drag flow. The dose-response curve of this type of assay had two remarkable features: (i) its ability to detect an output signal (i.e. bead number count) for very low Ag concentrations, and (ii) an output signal of the assay that was non-linear with respect to Ag concentration. We explain here the observed dose-response curves and show that the type of interactions and the concept of our assay are in favour of detecting the lowest analyte concentrations (where typically either zero or one Ag is carried per large bead), while higher concentrations are less efficiently detected. We propose a random walk process for the Ag-carrying bead over the magnetic landscape of small beads and this model description explains the enhanced overall capture probability of this assay and its particular non-linear dose response curves. PMID:25817550

  2. An assessment of non-linear dose response in chemiluminescence dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Jun, J.S. [Department of Physics, Chungnam National University, Taejon (Korea); Dalheimer, A.; Guggenberger, R. [Institute of Applied Radiation Protection, Federal Office of Radiation Protection, Oberschleissheim (Germany)

    2000-05-01

    Sugar and sorbite are well known to be convenient and suitable materials for chemiluminescence (CL) as well as electron spin resonance (ESR) dosimetry, in particular for retrospective dose assessment in an emergency and/or accident situation, mainly because of their close tissue-equivalence. In practice, however, the dose-CL response of those materials are not always shown to be satisfactorily linear. An attempt was made in this study to evaluate and correct the early supralinear dose-CL relationship appeared in the sugar and sorbite samples irradiated to gamma-ray doses of 0.5 to 10 Gy. In consideration of a similarity of the non-linear CL-dose relationship with the initial supralinearity shown in TL-dose response as depicted by Aitken, several recently proposed methods of expressing non-linear dose responses of TL, ESR or CL outputs were examined and investigated in order to look for a fittest means for the assessment of our supralinear dose-CL response of sugar and sorbite. As a result of an extensive study, merits and demerits of each method of representing non-linear dose response could be figured out in the light of our particular dose-CL relationship appeared in the sugar and sorbite samples. It is concluded that the 'supralinearity index', f(D), defined as a function of dose by Chen and McKeever is the most suitable function for expressing and correcting the non-linear dose-CL response shown in the initial low dose range of our irradiated sugar sorbite samples. The CL outputs corrected by use of f(D) are compared with those uncorrected, and the resultant CL sensitivities of the samples are numerically given together with re-evaluated dispersion of the sensitivities in terms of standard deviation. (author)

  3. Dose-response curves for fish MFO induction: How do we interpret different maxima and slopes?

    International Nuclear Information System (INIS)

    Induction of hepatic mixed function oxygenase (MFO) activity has been useful for screening effluents from pulp mills and oil refineries. Effluents and pure compounds can be assessed by direct fish exposure or by concentration with semipermeable membrane devices (SPMDs) and by measuring MFO in fish liver cell lines exposed to SPMD extracts. In these experiments, both fish and fish cells showed differences in slopes of dose-response curves, and in the maximal ethoxyresorufin-O-deethylase (EROD) activity. For example, TCDD elicits an EROD maxima of over 500 pmol/mg/min in PLHC-1 (Poeciliopsis lucida hepatocellular carcinoma cell line), while pulp mill and oil refinery effluent extracts showed maxima of 40 to 200 pmol/mg/min. Substituted phenanthrenes caused induction maxima of 100 pmol/mg/min. Similarly, in rainbow trout in vivo, TCDD and other chlorinated dioxins and furans induced up to 500 pmol/mg/min, whereas pulp mill and refinery effluents and substituted phenanthrenes produced EROD maxima of up to 100 pmol/mg/min. Differences in the slopes of dose-response curves were also common. In the current assessment of potencies, these diverse response curves are boiled-down to one number, the EC50 or other threshold-type of concentration. Comparisons of EC50s cannot express these differences and instead, ignore them. However, the authors realize there must be a better approach that takes into account these large differences in dose-response curve shape, slope and maxima. Interaction and discussions with modelers in the session will allow them to discuss various approaches to expressing the potencies of MFO inducers in fish

  4. Physical and biological factors determining the effective proton range

    Energy Technology Data Exchange (ETDEWEB)

    Grün, Rebecca [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390 (Germany); Medical Faculty of Philipps-University Marburg, Marburg 35032 (Germany); Friedrich, Thomas; Krämer, Michael; Scholz, Michael [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291 (Germany); Zink, Klemens [Institute of Medical Physics and Radiation Protection, University of Applied Sciences Gießen, Gießen 35390, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany); Durante, Marco [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt 64291, Germany and Department of Condensed Matter Physics, Darmstadt University of Technology, Darmstadt 64289 (Germany); Engenhart-Cabillic, Rita [Medical Faculty of Philipps-University Marburg, Marburg 35032, Germany and Department of Radiotherapy and Radiation Oncology, University Medical Center Giessen and Marburg, Marburg 35043 (Germany)

    2013-11-15

    Purpose: Proton radiotherapy is rapidly becoming a standard treatment option for cancer. However, even though experimental data show an increase of the relative biological effectiveness (RBE) with depth, particularly at the distal end of the treatment field, a generic RBE of 1.1 is currently used in proton radiotherapy. This discrepancy might affect the effective penetration depth of the proton beam and thus the dose to the surrounding tissue and organs at risk. The purpose of this study was thus to analyze the impact of a tissue and dose dependent RBE of protons on the effective range of the proton beam in comparison to the range based on a generic RBE of 1.1.Methods: Factors influencing the biologically effective proton range were systematically analyzed by means of treatment planning studies using the Local Effect Model (LEM IV) and the treatment planning software TRiP98. Special emphasis was put on the comparison of passive and active range modulation techniques.Results: Beam energy, tissue type, and dose level significantly affected the biological extension of the treatment field at the distal edge. Up to 4 mm increased penetration depth as compared to the depth based on a constant RBE of 1.1. The extension of the biologically effective range strongly depends on the initial proton energy used for the most distal layer of the field and correlates with the width of the distal penumbra. Thus, the range extension, in general, was more pronounced for passive as compared to active range modulation systems, whereas the maximum RBE was higher for active systems.Conclusions: The analysis showed that the physical characteristics of the proton beam in terms of the width of the distal penumbra have a great impact on the RBE gradient and thus also the biologically effective penetration depth of the beam.

  5. Redefining the relative biological effectiveness (RBE) in the context of the EQDX formalism

    International Nuclear Information System (INIS)

    Full text of publication follows. Objective: the relative biological effectiveness (RBE) of high-LET radiation (alpha-particles, e.g.) is defined as the ratio of the absorbed dose of a reference radiation (usually external beam) to a test radiation absorbed dose for a same biological endpoint, often a surviving fraction of cells. However, as it is currently defined, the RBE is dependent on the dosimetric end point as well as the dose values and is therefore limited in its utility, as a range of experimental values are often reported and it is unclear which value should be used in which context. We propose adoption of a quantity, called the RBE2, which relates the high-LET absorbed dose to 2-Gy fraction megavoltage external beam equivalents. Method: recently, the ICRU has promulgated the use of the equi-effective dose EQDX for bio-effect modeling of radiation responses. EQDX is defined as the total absorbed dose delivered by the external beam reference treatment plan of fraction size X that leads to the same biological effect as a test treatment plan. It was proposed that 2-Gy fractions of megavoltage X-rays should be the reference. Therefore, within this context relating the high-LET absorbed dose, not to a single fraction of external beam or β-emitter radiation, but to 2-Gy fraction external beam equivalent is a logical step, and more readily understood. We propose to call this new ratio RBE2, in keeping with the EQDX naming convention. Furthermore, for high-LET radiations typically used in nuclear medicine, α-particles and Auger electrons, the RBE2 value is dose-independent. The theoretical framework for the proposed new formalism is presented as is the application to two tumor cell lines. Results: the radiobiological parameters are obtained by fitting the curves to dose-response data from α-particle (213Bi) and β-particle (137Cs) radiation to two cell lines: a murine breast cancer cell line, NT2.5 and a human breast cancer cell line, MDA-MB-231. From these

  6. Dose response curve of the unsterilized products and the survival on the products

    International Nuclear Information System (INIS)

    Using the microbial radiation resistance distribution given by AAMI, the unsterilized fraction of the products was calculated at various bioburden levels, and the results obtained were shown in the dose response curves. With increasing microbical bioburden, the shoulder of the curves is becoming more remarkable. The appearance of the curves is resembled to that of multi-targets survival curves, and this fact can be realized from the analogy that the microbes on the products are to be the targets and the products are to be the cells in the target theory. (author)

  7. Dose response curve of the unsterilized products and the survival on the products

    Energy Technology Data Exchange (ETDEWEB)

    Oka, Mitsuru; Hosobuchi, Kazunari.

    1988-11-01

    Using the microbial radiation resistance distribution given by AAMI, the unsterilized fraction of the products was calculated at various bioburden levels, and the results obtained were shown in the dose response curves. With increasing microbical bioburden, the shoulder of the curves is becoming more remarkable. The appearance of the curves is resembled to that of multi-targets survival curves, and this fact can be realized from the analogy that the microbes on the products are to be the targets and the products are to be the cells in the target theory.

  8. Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.

    OpenAIRE

    Burns, Fredric J.; Uddin, Ahmed N.; Wu, Feng; Nádas, Arthur; Rossman, Toby G.

    2004-01-01

    The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experi...

  9. Biphasic Dose Response in Low Level Light Therapy – An Update

    OpenAIRE

    Huang, Ying-Ying; Sharma, Sulbha K.; Carroll, James; Hamblin, Michael R.

    2011-01-01

    Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenos...

  10. Negative dose-response relationship for radiation-induced micronuclei in polychromatic erythrocytes of mice

    International Nuclear Information System (INIS)

    Micronuclei were assessed among the bone marrow PCEs of mice 28 hr after exposures to 1 to 8 Gy of X-rays and at 6-hr intervals from 12-60 hr after exposures to 2 or 6 Gy. At 28 hr, the frequency of micronuclei declined as the exposure level increased from 1 to 8 Gy. The peak proportion of micronucleated PCEs appeared much later following 6 Gy than after 2 Gy exposures, implicating cell cycle delay as the cause of the negative dose-response relationship. 11 refs., 1 fig., 2 tabs

  11. Dose selection for prostate cancer patients based on dose comparison and dose response studies

    International Nuclear Information System (INIS)

    Purpose: To better define the appropriate dose for individual prostate cancer patients treated with three-dimensional conformal radiation therapy (3D CRT). Methods and Materials: Six hundred eighteen patients treated with 3D CRT between 4/89 and 4/97 with a median follow-up of 53 months are the subject of this study. The bNED outcomes were assessed by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. The patients were grouped into three groups by prostate-specific antigen (PSA) level (<10 ng/ml, 10-19.9 ng/ml, and 20+ ng/ml) and further subgrouped into six subgroups by favorable (T1, 2A and Gleason score ≤6 and no perineural invasion) and unfavorable characteristics (one or more of T2B, T3, Gleason 7-10, perineural invasion). Dose comparisons for bNED studies were made for each of the six subgroups by dividing patients at 76 Gy for all subgroups except the favorable <10 ng/ml subgroup, which was divided at 72.5 Gy. Five-year bNED rates were compared for the median dose of each dose comparison subgroup. Dose response functions were plotted based on 5-year bNED rates for the six patient groupings, with the data from each of the six subgroups divided into three dose groups. The 5-year bNED rate was also estimated using the dose response function and compares 73 Gy with 78 Gy. Results: Dose comparisons show a significant difference in 5-year bNED rates for three of the six subgroups but not for the favorable <10 ng/ml, the favorable 10-19.9 ng/ml, or the unfavorable ≥20 ng/ml subgroups. The significant differences ranged from 22% to 40% improvement in 5-year bNED with higher dose. Dose response functions show significant differences in 5-year bNED rates comparing 73 Gy and 78 Gy for four of the six subgroups. Again, no difference was observed for the favorable <10 ng/ml group or the unfavorable ≥20 ng/ml group. The significant differences observed in 5-year bNED ranged from 15% to 43%. Conclusions: Dose response varies by patient

  12. Investigating quartz optically stimulated luminescence dose-response curves at high doses

    Energy Technology Data Exchange (ETDEWEB)

    Lowick, Sally E., E-mail: lowick@geo.unibe.c [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Preusser, Frank [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Wintle, Ann G. [Institute of Geography and Earth Sciences, Aberystwyth University, AberystwythSY23 3DB (United Kingdom)

    2010-10-15

    Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose-response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose-response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the '325 {sup o}C' thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses

  13. Biological effects in intramuscular 239Pu administration during chelatotherapy

    International Nuclear Information System (INIS)

    Durable (up to 64 days) application of complexones (Ca and Zn DTPA) in the case of intramuscular administration of 239Pu large amounts in rats is studied. The results of studying the biological effect proving considerable decrease of the average lifespan of rats are given

  14. Biological Effects and Chemical Measurements in Irish Marine Waters

    OpenAIRE

    Giltrap, Michelle, (Thesis); McHugh, Brendan; Ronan, Jenny; Wilson, James; MCGOVERN Evin

    2014-01-01

    The overall aim of this project was to increase Ireland’s capacity for the generation of integrated monitoring of biological effects and chemical measurement data and for the completion of a pilot scale assessment of the quality of the Irish marine environment at a number of selected locations.

  15. Thermal effects of laser radiation in biological tissue.

    OpenAIRE

    Cummins, L; Nauenberg, M.

    1983-01-01

    A theoretical model is presented that simulates the thermal effects of laser radiation incident on biological tissue. The multiple scattering and absorption of the laser beam and the thermal diffusion process in the tissue are evaluated by a numerical technique that is well suited for microcomputers. Results are compared with recent empirical observations.

  16. Dose-response approaches for nuclear receptor-mediated modes of action for liver carcinogenicity: Results of a workshop

    Science.gov (United States)

    A public workshop, organized by a Steering Committee of scientists from government, industry, universities, and research organizations, was held at the National Institute of Environmental Health Sciences (NIEHS) in September, 2010. The workshop explored the dose-response implicat...

  17. Biological potential of extraterrestrial materials - 1. Nutrients in carbonaceous meteorites, and effects on biological growth

    Science.gov (United States)

    Mautner, Michael N.

    1997-06-01

    Soil nutrient analysis of the Murchison C2 carbonaceous chondrite shows biologically available S, P, Ca, Mg, Na, K and Fe and cation exchange capacity (CEC) at levels comparable with terrestrial agricultural soils. Weathering, and aqueous, hydrothermal (121°C, 15 min) and high-temperature (550°C, 3 h) processing increase the extractable nutrients. Extractable phosphorus (by 0.3 M NH 4F + 0.1 M HCl) content, which may be growth-limiting, is 6.3 μg g -1 in the unprocessed meteorite, but increases to 81 μg g -1 by hydrothermal processing and weathering, and to 130 μg g -1 by high temperature processing. The cation exchange capacity (CEC), attributed mainly to the organic fraction, corresponds responds to 345 meq per 100 g of the polymer, suggesting one ionizable COOH or OH group per 3-4 aromatic rings. The Allende C3(V) meteorite has low extractable Ca, Mg and K, in parallel to its low organic content and CEC, but high extractable P levels (160 μg g -1). Biological effects are observed on growth of the soil microorganisms Flavobacterium oryzihabitans and Nocardia asteroides in meteorite extracts, and the population levels suggest that P is the limiting nutrient. Effects on plant growth are examined on Solanum tuberosum (potato), where extracts of the Murchison meteorite lead to enhanced growth and pigmentation. The biologically available organic and inorganic nutrients in carbonaceous chondrites can provide concentrated solutions for prebiotic and early life processes, and serve as soils and fertilizers for future space-based biological expansion.

  18. Effects of weak magnetic fields on biological systems: physical aspects

    International Nuclear Information System (INIS)

    The effect of weak magnetic fields on biosystems is the subject matter of the science of magnetobiology. There are objective factors, due to theory lagging far behind experiment, that are hindering the development of this science. Academic interest in the subject is restrained by the fact that experimental data lack a clear physical explanation. Besides, there is a strong imbalance in how physics and biology are involved in magnetobiology, the former being still in infancy in this respect. It is this imbalance which is currently the driving force for the development of the theory of magnetobiology. This brief analytical review focuses on the physical aspects of magnetobiological research. The task of magnetobiology is to explore the biological effects of weak magnetic fields and to understand mechanisms behind these effects. Magnetobiology is part of a more general issue of the biological impact of weak and hyperweak physico-chemical factors. It is believed that such factors operate even below the trigger threshold for protective biological mechanisms and are therefore capable of accumulating at the subcellular level. The so-called 'kT-problem' is discussed in detail, and the interference mechanisms of the molecular gyroscope and of molecular states in an idealized protein cavity are suggested as candidate solutions. (reviews of topical problems)

  19. A kinetic model incorporating both localized and delocalized recombination: Application to the dependence of the TL dose response on photon energy

    Energy Technology Data Exchange (ETDEWEB)

    Eliyahu, I. [Ben Gurion University of the Negev, Beersheva 84105 (Israel); Soreq Nuclear Research Center, Yavne 81800 (Israel); Horowitz, Y.S., E-mail: yigalho@gmail.com [Soreq Nuclear Research Center, Yavne 81800 (Israel); Oster, L. [Sami Shamoon College of Engineering, Beersheva 84100 (Israel); Mardor, I. [Soreq Nuclear Research Center, Yavne 81800 (Israel)

    2014-01-15

    electron tracks and the onset and relative importance of intra-track versus inter-track recombination. -- Highlights: • Development of a kinetic model of thermoluminescence dose response was achieved. • The effects of ionization density were included to explain the behaviour of supralinearity with photon energy. • Electron–hole population of spatially correlated defects in irradiation stage was incorporated based on nanodosimetric considerations.

  20. A kinetic model incorporating both localized and delocalized recombination: Application to the dependence of the TL dose response on photon energy

    International Nuclear Information System (INIS)

    -track versus inter-track recombination. -- Highlights: • Development of a kinetic model of thermoluminescence dose response was achieved. • The effects of ionization density were included to explain the behaviour of supralinearity with photon energy. • Electron–hole population of spatially correlated defects in irradiation stage was incorporated based on nanodosimetric considerations

  1. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

    OpenAIRE

    Pareren, Y.; Houdijk, M.; Jansen, Maarten; Reeser, M.; Mulder, Paul; Hokken-Koelega, Anita

    2003-01-01

    textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly assigned to treatment with either 3 IU (group A) or 6 IU (group B) GH/m(2).d ( approximately 0.033 or 0.067 mg/kg.d, respectively). The mean (+/-SD) birth length was -3.6 (1.4), the age at the start of the study was 8...

  2. Dose-response study on thyrotoxic patients undergoing positron emission tomography and radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Flower, M.A. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); Al-Saadi, A. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); Harmer, C.L. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); McCready, V.R. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); Ott, R.J. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom))

    1994-06-01

    Our policy had been to give 75 MBq iodine-131 at 6-monthly intervals to patients with Graves' disease until they became euthyroid. Since PET has been available at this hospital, the radiation dose to the thyroid has been calculated with an accuracy of -20%, the thyroid mass being determined from an iodine-124 PET scan. A dose-response study has been carried out on 65 patients who have received single or cumulative radiation doses of < 80 Gy. The results show that patients who receive a low radiation dose (< 20 Gy) at their first treatment have a high probability of remaining toxic at 12 months. In contrast, patients who receive higher radiation doses (> 40 Gy) at their first treatment have a high probability of control. The probability of becoming euthyroid increases more rapidly with increasing radiation dose than the probability of becoming hypothyroid. Following this dose-response study, a new treatment protocol has been introduced. A [sup 124]I PET tracer study prior to [sup 131]I therapy will be performed to enable a prescribed thyroid dose of 50 Gy to be delivered to patients with Graves' disease. Further [sup 131]I therapy will be considered if patients are still toxic at 12 months. (orig./MG)

  3. Does a dose-response relation exist between spinal pain and temporomandibular disorders?

    Directory of Open Access Journals (Sweden)

    Englund Erling

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to test whether a reciprocal dose-response relation exists between frequency/severity of spinal pain and temporomandibular disorders (TMD. Methods A total of 616 subjects with varying severity of spinal pain or no spinal pain completed a questionnaire focusing on symptoms in the jaw, head and spinal region. A subset of the population (n = 266 were sampled regardless of presence or absence of spinal pain. We used two different designs, one with frequency/severity of spinal pain, and the other, with frequency/severity of TMD symptoms as independent variable. All 616 participants were allocated to four groups, one control group without spinal pain and three spinal pain groups. The subjects in the subset were allocated to one control group without TMD symptoms and three TMD groups. Odds ratios (ORs were calculated for presence of frequent TMD symptoms in the separate spinal pain groups as well as for frequent spinal pain in the separate TMD groups. Results The analysis showed increasing ORs for TMD with increasing frequency/severity of spinal pain. We also found increasing ORs for spinal pain with increasing frequency/severity of TMD symptoms. Conclusion This study shows a reciprocal dose-response-like relationship between spinal pain and TMD. The results indicate that these two conditions may share common risk factors or that they may influence each other. Studies on the temporal sequence between spinal pain and TMD are warranted.

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

    International Nuclear Information System (INIS)

    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)

  5. Effect of biologic agents on radiographic progression of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Gabriel J Tobón

    2010-08-01

    Full Text Available Gabriel J Tobón1, Alain Saraux1,2, Valérie Devauchelle-Pensec1,21Immunology Laboratory, Morvan Hospital, Université de Bretagne Occidentale, Brest, France; 2Rheumatology Unit, Hôpital de la Cavale Blanche, CHU Brest, FranceAbstract: The treatment of rheumatoid arthritis (RA has benefited over the last few years from the introduction of biologic agents whose development was based on new insights into the immunological factors involved in the pathogenesis of RA and the development of joint damage. These biological agents have been proven effective in RA patients with inadequate responses to synthetic disease-modifying antirheumatic drugs (DMARDs. Preventing joint damage is now the primary goal of RA treatment, and guidelines exist for the follow-up of joint abnormalities. Most biologic agents produced high clinical and radiological response rates in patients with established or recent-onset RA. Thus, for the first time, obtaining a remission is a reasonable treatment goal in RA patients. Factors that are crucial to joint damage control are: early initiation of DMARDs, use of intensive treatments including biological agents, and close monitoring of clinical disease activity and radiographic progression. However, some patients remain unresponsive to all available treatments and continue to experience joint damage progression. A major objective now is to identify patients at high risk for severe joint damage, in order to tailor the treatment regimen to their specific needs.Keywords: rheumatoid arthritis, radiographic progression, biologics

  6. Predictive modeling of nanomaterial exposure effects in biological systems

    Directory of Open Access Journals (Sweden)

    Liu X

    2013-09-01

    Full Text Available Xiong Liu,1 Kaizhi Tang,1 Stacey Harper,2 Bryan Harper,2 Jeffery A Steevens,3 Roger Xu1 1Intelligent Automation, Inc., Rockville, MD, USA; 2Department of Environmental and Molecular Toxicology, School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USA; 3ERDC Environmental Laboratory, Vicksburg, MS, USA Background: Predictive modeling of the biological effects of nanomaterials is critical for industry and policymakers to assess the potential hazards resulting from the application of engineered nanomaterials. Methods: We generated an experimental dataset on the toxic effects experienced by embryonic zebrafish due to exposure to nanomaterials. Several nanomaterials were studied, such as metal nanoparticles, dendrimer, metal oxide, and polymeric materials. The embryonic zebrafish metric (EZ Metric was used as a screening-level measurement representative of adverse effects. Using the dataset, we developed a data mining approach to model the toxic endpoints and the overall biological impact of nanomaterials. Data mining techniques, such as numerical prediction, can assist analysts in developing risk assessment models for nanomaterials. Results: We found several important attributes that contribute to the 24 hours post-fertilization (hpf mortality, such as dosage concentration, shell composition, and surface charge. These findings concur with previous studies on nanomaterial toxicity using embryonic zebrafish. We conducted case studies on modeling the overall effect/impact of nanomaterials and the specific toxic endpoints such as mortality, delayed development, and morphological malformations. The results show that we can achieve high prediction accuracy for certain biological effects, such as 24 hpf mortality, 120 hpf mortality, and 120 hpf heart malformation. The results also show that the weighting scheme for individual biological effects has a significant influence on modeling the overall impact of

  7. Evaluation of radiobiological effects in 3 distinct biological models

    International Nuclear Information System (INIS)

    Full text of publication follows. The present work aims at sharing the process of development of advanced biological models to study radiobiological effects. Recognizing several known limitations and difficulties of the current monolayer cellular models, as well as the increasing difficulties to use advanced biological models, our group has been developing advanced biological alternative models, namely three-dimensional cell cultures and a less explored animal model (the Zebra fish - Danio rerio - which allows the access to inter-generational data, while characterized by a great genetic homology towards the humans). These 3 models (monolayer cellular model, three-dimensional cell cultures and zebra fish) were externally irradiated with 100 mGy, 500 mGy or 1 Gy. The consequences of that irradiation were studied using cellular and molecular tests. Our previous experimental studies with 100 mGy external gamma irradiation of HepG2 monolayer cells showed a slight increase in the proliferation rate 24 h, 48 h and 72 h post irradiation. These results also pointed into the presence of certain bystander effects 72 h post irradiation, constituting the starting point for the need of a more accurate analysis realized with this work. At this stage, we continue focused on the acute biological effects. Obtained results, namely MTT and clonogenic assays for evaluating cellular metabolic activity and proliferation in the in vitro models, as well as proteomics for the evaluation of in vivo effects will be presented, discussed and explained. Several hypotheses will be presented and defended based on the facts previously demonstrated. This work aims at sharing the actual state and the results already available from this medium-term project, building the proof of the added value on applying these advanced models, while demonstrating the strongest and weakest points from all of them (so allowing the comparison between them and to base the subsequent choice for research groups starting

  8. Radiolabelled substrates for studying biological effects of trace contaminants

    International Nuclear Information System (INIS)

    A programme of coordinated isotopic tracer-aided investigations of the biological side-effects of foreign chemical residues in food and agriculture, initiated in 1973, was reviewed. The current status of representative investigations from the point of view of techniques and priorities was assessed. Such investigations involved radioactive substrates for studying DNA injury and its repair; 14C-labelled acetylcholine as substrate for measuring enzyme inhibition due to the presence of, or exposure to, anticholinesteratic contaminants; radioactive substrates as indication of side-effects in non-target organisms and of their comparative susceptibilities; radioactive substrates as indicators of persistence or biodegradability of trace contaminants of soil or water; and labelled pools for studying the biological side-effects of trace contaminants. Priorities were identified

  9. ESTIMATING A DOSE-RESPONSE RELATIONSHIP BETWEEN LENGTH OF STAY AND FUTURE RECIDIVISM IN SERIOUS JUVENILE OFFENDERS.

    Science.gov (United States)

    Loughran, Thomas A; Mulvey, Edward P; Schubert, Carol A; Fagan, Jeffrey; Piquero, Alex R; Losoya, Sandra H

    2009-01-01

    The effect of sanctions on subsequent criminal activity is of central theoretical importance in criminology. A key question for juvenile justice policy is the degree to which serious juvenile offenders respond to sanctions and/or treatment administered by the juvenile court. The policy question germane to this debate is finding the level of confinement within the juvenile justice system that maximizes the public safety and therapeutic benefits of institutional confinement. Unfortunately, research on this issue has been limited with regard to serious juvenile offenders. We use longitudinal data from a large sample of serious juvenile offenders from two large cities to 1) estimate a causal treatment effect of institutional placement, as opposed to probation, on future rate of rearrest and 2) investigate the existence of a marginal effect (i.e., benefit) for longer length of stay once the institutional placement decision had been made. We accomplish the latter by determining a dose-response relationship between the length of stay and future rates of rearrest and self-reported offending. The results suggest that an overall null effect of placement exists on future rates of rearrest or self-reported offending for serious juvenile offenders. We also find that, for the group placed out of the community, it is apparent that little or no marginal benefit exists for longer lengths of stay. Theoretical, empirical, and policy issues are outlined. PMID:20052309

  10. ESTIMATING A DOSE-RESPONSE RELATIONSHIP BETWEEN LENGTH OF STAY AND FUTURE RECIDIVISM IN SERIOUS JUVENILE OFFENDERS*

    Science.gov (United States)

    Loughran, Thomas A.; Mulvey, Edward P.; Schubert, Carol A.; Fagan, Jeffrey; Piquero, Alex R.; Losoya, Sandra H.

    2009-01-01

    The effect of sanctions on subsequent criminal activity is of central theoretical importance in criminology. A key question for juvenile justice policy is the degree to which serious juvenile offenders respond to sanctions and/or treatment administered by the juvenile court. The policy question germane to this debate is finding the level of confinement within the juvenile justice system that maximizes the public safety and therapeutic benefits of institutional confinement. Unfortunately, research on this issue has been limited with regard to serious juvenile offenders. We use longitudinal data from a large sample of serious juvenile offenders from two large cities to 1) estimate a causal treatment effect of institutional placement, as opposed to probation, on future rate of rearrest and 2) investigate the existence of a marginal effect (i.e., benefit) for longer length of stay once the institutional placement decision had been made. We accomplish the latter by determining a dose-response relationship between the length of stay and future rates of rearrest and self-reported offending. The results suggest that an overall null effect of placement exists on future rates of rearrest or self-reported offending for serious juvenile offenders. We also find that, for the group placed out of the community, it is apparent that little or no marginal benefit exists for longer lengths of stay. Theoretical, empirical, and policy issues are outlined. PMID:20052309

  11. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

    Science.gov (United States)

    Goeorge, Kerry; Cucinotta, Francis A.

    2007-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from 51 to 184 keV/micron and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected at G2 and mitosis in first division post irradiation after chromosomes were prematurely condensed using calyculin-A. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 9 to 35. The RBE values increased with LET, reaching a maximum for the 600 MeV/n Fe ions with LET of 184 keV/micron. When the LET of the primary beam was below approximately 100 keV/micron, the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of primary beams was higher than 100 keV/micron. The yield of aberrations correlated with the dose-average LET of the beam after traversal through the shielding.

  12. The Biological Effectiveness of Silicon Ions is Significantly Higher than Iron Ions for the Induction of Chromosome Damage in Human Lymphocytes

    Science.gov (United States)

    George, Kerry; Hada, Megumi; Cucinotta, F. A.

    2010-01-01

    Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, or Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Fe beams in this study ranged from 145 to 440 keV/micron and the LET Si ions ranged from 48 to 158 keV/micron. Doses delivered were in the 10 to 200 cGy range. Dose response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The estimates of RBE(sub max) values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBE(sub max) value for Fe ions was obtained with the 600 Mev/u beam and 170 MeV/u beam produced the highest RBE(sub max) value for Si ions. For both ions the RBE(sub max) values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreased with further increase in LET.

  13. Exposure dose response relationships of the freshwater bivalve Hyridella australis to cadmium spiked sediments

    Energy Technology Data Exchange (ETDEWEB)

    Marasinghe Wadige, Chamani P.M., E-mail: chamani.marasinghe.wadige@canberra.edu.au; Maher, William A.; Taylor, Anne M.; Krikowa, Frank

    2014-07-01

    Highlights: • The exposure–dose–response approach was used to assess cadmium exposure and toxicity. • Accumulated cadmium in H. australis reflected the sediment cadmium exposure. • Spill over of cadmium into the biologically active pool was observed. • Increased cadmium resulted in measurable biological effects. • H. australis has the potential to be a cadmium biomonitor in freshwater environments. - Abstract: To understand how benthic biota may respond to the additive or antagonistic effects of metal mixtures in the environment it is first necessary to examine their responses to the individual metals. In this context, laboratory controlled single metal-spiked sediment toxicity tests are useful to assess this. The exposure–dose–response relationships of Hyridella australis to cadmium-spiked sediments were, therefore, investigated in laboratory microcosms. H. australis was exposed to individual cadmium spiked sediments (<0.05 (control), 4 ± 0.3 (low) and 15 ± 1 (high) μg/g dry mass) for 28 days. Dose was measured as cadmium accumulation in whole soft body and individual tissues at weekly intervals over the exposure period. Dose was further examined as sub-cellular localisation of cadmium in hepatopancreas tissues. The biological responses in terms of enzymatic and cellular biomarkers were measured in hepatopancreas tissues at day 28. H. australis accumulated cadmium from spiked sediments with an 8-fold (low exposure organisms) and 16-fold (high exposure organisms) increase at day 28 compared to control organisms. The accumulated tissue cadmium concentrations reflected the sediment cadmium exposure at day 28. Cadmium accumulation in high exposure organisms was inversely related to the tissue calcium concentrations. Gills of H. australis showed significantly higher cadmium accumulation than the other tissues. Accumulated cadmium in biologically active and biologically detoxified metal pools was not significantly different in cadmium exposed

  14. Biological effects of exposure to magnetic resonance imaging: an overview

    Directory of Open Access Journals (Sweden)

    Formica Domenico

    2004-04-01

    Full Text Available Abstract The literature on biological effects of magnetic and electromagnetic fields commonly utilized in magnetic resonance imaging systems is surveyed here. After an introduction on the basic principles of magnetic resonance imaging and the electric and magnetic properties of biological tissues, the basic phenomena to understand the bio-effects are described in classical terms. Values of field strengths and frequencies commonly utilized in these diagnostic systems are reported in order to allow the integration of the specific literature on the bio-effects produced by magnetic resonance systems with the vast literature concerning the bio-effects produced by electromagnetic fields. This work gives an overview of the findings about the safety concerns of exposure to static magnetic fields, radio-frequency fields, and time varying magnetic field gradients, focusing primarily on the physics of the interactions between these electromagnetic fields and biological matter. The scientific literature is summarized, integrated, and critically analyzed with the help of authoritative reviews by recognized experts, international safety guidelines are also cited.

  15. Dose response of selected ion chambers in applied homogeneous transverse and longitudinal magnetic fields

    International Nuclear Information System (INIS)

    Purpose: The magnetic fields of an integrated MR-Linac system will alter the paths of electrons that produce ions in the ionization chambers. The dose response of selected ion chambers is evaluated in the presence of varying transverse and longitudinal magnetic fields. The investigation is useful in calibration of therapeutic x-ray beams associated with MR-Linac systems. Methods: The Monte Carlo code PENELOPE was used to model the irradiation of NE2571, and PR06C ionization chambers in the presence of a transverse and longitudinal (with respect to the photon beam) magnetic fields of varying magnitude. The long axis of each chamber was simulated both parallel and perpendicular to the incident photon beam for each magnetic field case. The dose deposited in each chamber for each case was compared to the case with zero magnetic field by means of a ratio. The PR06C chamber's response was measured in the presence of a transverse magnetic field with field strengths ranging from 0.0 to 0.2 T to compare to simulated results. Results: The simulations and measured data show that in the presence of a transverse magnetic field there is a considerable dose response (maximum of 11% near 1.0 T in the ion chambers investigated, which depends on the magnitude of magnetic field, and relative orientation of the magnetic field, radiation beam, and ion chamber. Measurements made with the PR06C chamber verify these results in the region of measurement. In contrast, a longitudinal magnetic field produces only a slight increase in dose response (2% at 1.5 T) that rises slowly with increasing magnetic field and is seemingly independent of chamber orientation. Response trends were similar for the two ion chambers and relative orientations considered, but slight variations are present from chamber to chamber. Conclusions: Care must be taken when making ion chamber measurements in a transverse magnetic field. Ion chamber responses vary not only with transverse field strength, but with chamber

  16. Biological effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Few weeks ago, when the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) submitted to the U.N. General Assembly the UNSCEAR 1994 report, the international community had at its disposal a broad view of the biological effects of low doses of ionizing radiation. The 1994 report (272 pages) specifically addressed the epidemiological studies of radiation carcinogenesis and the adaptive responses to radiation in cells and organisms. The report was aimed to supplement the UNSCEAR 1993 report to the U.N. General Assembly- an extensive document of 928 pages-which addressed the global levels of radiation exposing the world population, as well as some issues on the effects of ionizing radiation, including: mechanisms of radiation oncogenesis due to radiation exposure, influence of the level of dose and dose rate on stochastic effects of radiation, hereditary effects of radiation effects on the developing human brain, and the late deterministic effects in children. Those two UNSCEAR reports taken together provide an impressive overview of current knowledge on the biological effects of ionizing radiation. This article summarizes the essential issues of both reports, although it cannot cover all available information. (Author)

  17. Advances in the biological effects of terahertz wave radiation.

    Science.gov (United States)

    Zhao, Li; Hao, Yan-Hui; Peng, Rui-Yun

    2014-01-01

    The terahertz (THz) band lies between microwave and infrared rays in wavelength and consists of non-ionizing radiation. Both domestic and foreign research institutions, including the army, have attached considerable importance to the research and development of THz technology because this radiation exhibits both photon-like and electron-like properties, which grant it considerable application value and potential. With the rapid development of THz technology and related applications, studies of the biological effects of THz radiation have become a major focus in the field of life sciences. Research in this field has only just begun, both at home and abroad. In this paper, research progress with respect to THz radiation, including its biological effects, mechanisms and methods of protection, will be reviewed. PMID:25722878

  18. Advances in the biological effects of terahertz wave radiation

    Institute of Scientific and Technical Information of China (English)

    Li Zhao; Yan-Hui Hao; Rui-Yun Peng

    2014-01-01

    The terahertz (THz) band lies between microwave and infrared rays in wavelength and consists of non-ionizing radiation. Both domestic and foreign research institutions, including the army, have attached considerable importance to the research and development of THz technology because this radiation exhibits both photon-like and electron-like properties, which grant it considerable application value and potential. With the rapid development of THz technology and related applications, studies of the biological effects of THz radiation have become a major focus in the field of life sciences. Research in this field has only just begun, both at home and abroad. In this paper, research progress with respect to THz radiation, including its biological effects, mechanisms and methods of protection, will be reviewed.

  19. Oxygen effect in radiation biology: caffeine and serendipity

    International Nuclear Information System (INIS)

    The 'hit theory' developed in 1920s to explain the actions of ionizing radiation on cells and organisms was purely physical, and its limitation was its inadequacy to address the contemporary findings such as the oxygen enhancement of radiobiological damage, and the increased radio- sensitivity of dividing compared to non-dividing cells. The textbooks written prior to 1970s did not either refer at all to oxygen as a radiosensitizer, or had mentioned it only in a passing manner; yet 'oxygen effect' was emerging as the central dogma in radiation biology. The oxygen effect in radiation biology is highly interdisciplinary encompassing atomic physics (i.e. interaction of photon with matter), radiation chemistry (formation of reactive oxygen species), molecular signalling, gene expression and genetic alterations in cells (mutation, cancer) or the cell death (apoptosis, necrosis, mitotic catastrophe, etc.). Cell death in higher organisms is now recognized as the precursor of possible error-free cell replacement repair. (author)

  20. Biological effect of nitrogen ion implantation on stevia

    International Nuclear Information System (INIS)

    Dry seed of stevia were implanted by 35∼150 keV nitrogen ions with various doses. The biological effect in M1 was studied. The results showed that nitrogen ion beam was able to induce variation on chromosome structure in root tip cells. The rate of cells with chromosome aberration was increased with ion beam energy and dose added, but there was on significant linear regression relationship between ion dose and aberration rate. The results indicated the seedling height reduced with the increasing of dose for ion beam. The biological effect of nitrogen ion beam on M1 stevia was lower than that of γ-rays. (6 refs., 1 fig., 4 tabs.)

  1. Biological effects of space loading on salvia miltiorrhiza

    International Nuclear Information System (INIS)

    To study the SP1 biological effects of space loading on Salvia miltiorrhiza seeds. Dry seeds were carried by breeding satellite-Shijian 8, and seeds were sowed in the field after returning the ground. Some parameters were measured, such as growth stage, seed vigor, plant traits above ground, root feature and seeding characteristics. Variation of DNA was tested by SRAP. The results showed that DNA variation happened, the rate of germination and emergence in SP1 generation increased significantly, the blooming date was advanced, rachis length and flower number of SP1 generation also increased compared with CK. At the same time, the root features and seeding characteristics were improved, the CV was increased in the relative traits, but leaf growth was inhibited significantly. The biological effects of space loading on dry seed of Salvia miltiorrhiza might be an important index for germplasm improvement and breeding. (authors)

  2. Effects of UV and microwave radiation on biological material

    International Nuclear Information System (INIS)

    For the present study, ten publications on the effect of UV radiation were analyzed. In vitro tests were carried out with one biological substance and seven different human or animal organs and biocytocultures. In vivo, three bacterial strains were irradiated and four irradiation experiments were carried out on mice. As to the effect of microwave radiation, eleven publications were analyzed. In vitro tests were carried out with one biological substance and three animal organs. In vivo, one bacterial strain was irradiated and eight irradiation experiments were carried out on different types of animals. The study's aim was to obtain a survey on biochemical changes of the organisms. Phenomenological changes were given only when the corresponding articles contained further investigation results. Behavioral changes were not taken into account. The results published by the authors of the original papers were compiled in a kind of dictionary. All relevant data are listed in a defined order. (orig.)

  3. Biological effects of low-intensity millimetric radiation

    Energy Technology Data Exchange (ETDEWEB)

    Betskiy, O.V.; Putvinskiy, A.V.

    1986-10-01

    The authors discuss a possible role of strong absorption of millimetric (MM) waves by water molecules in the primary mechanism of the reaction of biological systems to MM irradiation. Data are given on the interaction of MM radiation with simple aqueous systems. Primary attention is given to the phenomenon of convective mixing of aqueous solutions under the effect of low-intensity MM waves (1 ... 10 mW/cm/sup 2/). 12 references, 6 figures.

  4. On Quantum Effects in a Theory of Biological Evolution

    OpenAIRE

    Martin-Delgado M.A.

    2012-01-01

    We construct a descriptive toy model that considers quantum effects on biological evolution starting from Chaitin's classical framework. There are smart evolution scenarios in which a quantum world is as favorable as classical worlds for evolution to take place. However, in more natural scenarios, the rate of evolution depends on the degree of entanglement present in quantum organisms with respect to classical organisms. If the entanglement is maximal, classical evolution turns out to be more...

  5. BIOLOGICAL EFFECTS OF PULSED SHORT WAVE TREATMENT. AN EXPERIMENTAL STUDY

    OpenAIRE

    Dogaru Gabriela; Crăciun Constantin

    2015-01-01

    Pulsed short waves are short electromagnetic waves emitted as intermittent trains with a fixed duration, separated by free intervals of variable duration. The biological effects of pulsed short waves could be explained according to most of the authors by an activation of cellular enzymatic reactions, a stimulation of energy metabolism, a stimulation of liver function, of adrenal gland function and of the reticulocyte system, changes in cell permeability, by an increase of peripheral blood flo...

  6. Metabolism and biological effects of alpha-emitting radionuclides

    International Nuclear Information System (INIS)

    The emphasis of much of the current and planned research on the toxicity of alpha-emitting radionuclides is directed toward the complexities of actual and potential conditions of occupational environmental exposures of human beings. These, as well as the more limited studies on mechanisms of biological transport and effects, should increase our ability to predict health risks more accurately and to deal more confidently with human exposures, if and when they occur

  7. Biological effects of the ionizing radiation. Press breakfast

    International Nuclear Information System (INIS)

    This document brings together the subjects discussed during the Press breakfast of 29 june 2000 on the biological effects of the ionizing radiations, with scientists of the CEA and the CNRS. It presents the research programs and provides inquiries on the NDA operating to introduce the NDA damages by ionizing radiations, the possible repairs and the repair efficiency facing the carcinogenesis. Those researches allow the scientists to define laws on radiation protection. (A.L.B.)

  8. Biological Effects of Phosphate on Fibroblast-Like Synoviocytes

    OpenAIRE

    Yubo Sun; Mauerhan, David R.; Deepthi Chaturvedi; Hanley, Edward N; Gruber, Helen E.

    2012-01-01

    This study sought to examine the expression of genes implicated in phosphate transport and pathological calcification in osteoarthritis (OA) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and investigate the biological effects of phosphate. Results revealed that several genes, which were implicated in phosphate transport and pathological calcification, were differentially expressed in OA FLS and RA FLS. Phosphate stimulated the expression of matrix metalloproteinse-1, matrix...

  9. Effects of biological sex on the pathophysiology of the heart

    OpenAIRE

    Fazal, Loubina; Azibani, Feriel; Vodovar, Nicolas; Cohen Solal, Alain; Delcayre, Claude; Samuel, Jane-Lise

    2014-01-01

    Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex-specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac structure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the response of th...

  10. The Enigma of Linear/Supralinear Thermoluminescence Dose Response Mixed Localized/Delocalized Recombination describes a Solution

    International Nuclear Information System (INIS)

    Kinetic models of thermoluminescence (TL) dose response have recently been proposed which propose to solve the long-standing conundrumconcerning the dependence of the TL dose response on ionization density. Many TL materials exhibit an initially linear dose response over several decades of dose which then turns supralinear before entering into saturation. LiF:Mg,Ti is perhaps the most outstanding and widely studied example. The dose response of the major dosimetric glow peak is strictly linear from the lowest level of dose measurable of ~10-4 Gy to ~ 1 Gy and then turns supralinear reaching maximum values of the normalized TL dose response f(D) of 3-5 at levels of dose between 300 -500 Gy .This behaviour coupled with the dependence of the supralinearity on particle type and energy (i.e., on ionization density) has presented a formidable challenge to conventional kinetic theories of dose response. It has been gradually recognized over the past decade that this behaviour in LiF:Mg,Ti requires both nanodosimetric input coupled with a mixture of both localized and delocalized recombination mechanisms. This due to the complex nature of the trapping structure giving rise to the TL. Following irradiation the trapping center (TC)- luminescent center (LC) can be populated by a locally trapped electron-hole (e-h) or an electron (e) only. The former giving rise to geminate (localized) recombination the latter to mainly delocalized recombination via charge transfer migration in the conduction band. The relative concentrations of these configurations are dependent on ionization density. In this paper we present the latest developments in which we attempt to simulate the linear/supralinear dose response, the dependence of the supralinearity on electron energy and the shape of composite glow peak 5 as a function of electron energy. In order to predict all three characteristics the simulations require the incorporation of band tail states allowing semi-localized recombination from

  11. Effect of Ceramic Scaffold Architectural Parameters on Biological Response

    Directory of Open Access Journals (Sweden)

    Maria Isabella eGariboldi

    2015-10-01

    Full Text Available Numerous studies have focused on the optimization of ceramic architectures to fulfill a variety of scaffold functional requirements and improve biological response. Conventional fabrication techniques, however, do not allow for the production of geometrically controlled, reproducible structures and often fail to allow the independent variation of individual geometric parameters. Current developments in additive manufacturing technologies suggest that 3D printing will allow a more controlled and systematic exploration of scaffold architectures. This more direct translation of design into structure requires a pipeline for design-driven optimization. A theoretical framework for systematic design and evaluation of architectural parameters on biological response is presented. Four levels of architecture are considered, namely (1 surface topography, (2 pore size and geometry, (3 porous networks and (4 macroscopic pore arrangement, including the potential for spatially varied architectures. Studies exploring the effect of various parameters within these levels are reviewed. This framework will hopefully allow uncovering of new relationships between architecture and biological response in a more systematic way, as well as inform future refinement of fabrication techniques to fulfill architectural necessities with a consideration of biological implications.

  12. Evolutionary tradeoffs between economy and effectiveness in biological homeostasis systems.

    Directory of Open Access Journals (Sweden)

    Pablo Szekely

    Full Text Available Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals.

  13. Lung function, biological monitoring, and biological effect monitoring of gemstone cutters exposed to beryls

    Science.gov (United States)

    Wegner, R.; Heinrich-Ramm, R.; Nowak, D.; Olma, K.; Poschadel, B.; Szadkowski, D.

    2000-01-01

    OBJECTIVES—Gemstone cutters are potentially exposed to various carcinogenic and fibrogenic metals such as chromium, nickel, aluminium, and beryllium, as well as to lead. Increased beryllium concentrations had been reported in the air of workplaces of beryl cutters in Idar-Oberstein, Germany. The aim of the survey was to study the excretion of beryllium in cutters and grinders with occupational exposure to beryls—for example, aquamarines and emeralds—to examine the prevalence of beryllium sensitisation with the beryllium lymphocyte transformation test (BeLT), to examine the prevalence of lung disease induced by beryllium, to describe the internal load of the respective metals relative to work process, and to screen for genotoxic effects in this particular profession.
METHODS—In a cross sectional investigation, 57 out of 100 gemstone cutters working in 12 factories in Idar-Oberstein with occupational exposure to beryls underwent medical examinations, a chest radiograph, lung function testing (spirometry, airway resistance with the interrupter technique), and biological monitoring, including measurements of aluminium, chromium, and nickel in urine as well as lead in blood. Beryllium in urine was measured with a newly developed direct electrothermal atomic absorption spectroscopy technique with a measurement limit of 0.06 µg/l. Also, cytogenetic tests (rates of micronuclei and sister chromatid exchange), and a BeLT were performed. Airborne concentrations of beryllium were measured in three factories. As no adequate local control group was available, the cutters were categorised into those with an exposure to beryls of >4 hours/week (group A) and ⩽4 hours/week (group B).
RESULTS—Clinical, radiological, or spirometric abnormalities indicating pneumoconiosis were detected in none of the gemstone cutters. Metal concentrations in biological material were far below the respective biological limit values, and beryllium in urine was only measurable in

  14. The influence of parameters of A-type carbonated apatites synthesis on radiation dose response

    International Nuclear Information System (INIS)

    The aim of this work is the investigation of dose response of A-type carbonated apatites prepared in different conditions. Irradiated samples prepared with carbonate content of 1.45 to 4.84% are studied by using electron paramagnetic resonance (EPR). The EPR spectra are mainly constituted of lines associated to axial CO2- species (gperp = 2.0028 and g// = 1.9973) and CO3- species (g1 = 2,0170, g2 = 2,0090 e g3 = 2,0041). The production of CO2- species on gamma irradiation depends on the carbonate concentration and the hydroxyapatite stoichiometry. The lowest dose detection limit was achieved with stoichiometric samples and carbonate content around of 3.7%. (author)

  15. Dose response of xylitol and sorbitol for epr retrospective dosimetry with applications to chewing gum

    International Nuclear Information System (INIS)

    The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD). (authors)

  16. Summary of dosimetry, pathology, and dose response for bone sarcomas in beagles injected with radium-226

    International Nuclear Information System (INIS)

    In the completed 226Ra portion of a 30-year-long experiment to determine the relative radiotoxicity of injected 226Ra and 239Pu, 42 of 116 animals injected with 226Ra developed 63 bone sarcomas; none were observed in 44 controls. Average alpha plus beta dose to the skeleton to death was calculated on the basis of mathematical functions developed from sequential measurements of radium and radon retention in each dog. Bone sarcomas were identified radiographically or clinically, with subsequent histopathological confirmation and classification. Most primary bone tumors were classified as osteosarcomas if osteoid arose from a malignant stroma. The dose-response curve over the six lowest injected dose levels fits well to a linear, no-threshold, least squares fit, through a control incidence of 0.8%, and with a slope of 0.042% incidence per rad. 19 refs., 5 figs., 2 tabs

  17. Dose response of surfactants to attenuate gas embolism related platelet aggregation

    Science.gov (United States)

    Eckmann, David M.; Eckmann, Yonaton Y.; Tomczyk, Nancy

    2014-03-01

    Intravascular gas embolism promotes blood clot formation, cellular activation, and adhesion events, particularly with platelets. Populating the interface with surfactants is a chemical-based intervention to reduce injury from gas embolism. We studied platelet activation and platelet aggregation, prominent adverse responses to blood contact with bubbles. We examined dose-response relationships for two chemically distinct surfactants to attenuate the rise in platelet function stimulated by exposure to microbubbles. Significant reduction in platelet aggregation and platelet activation occurred with increasing concentration of the surfactants, indicating presence of a saturable system. A population balance model for platelet aggregation in the presence of embolism bubbles and surfactants was developed. Monte Carlo simulations for platelet aggregation were performed. Results agree qualitatively with experimental findings. Surfactant dose-dependent reductions in platelet activation and aggregation indicate inhibition of the gas/liquid interface's ability to stimulate cellular activation mechanically.

  18. Dose response characteristics of polymethacrylic acid gel (PMAAG) for a polymerization-based dosimeter using NMR.

    Science.gov (United States)

    Iskandar, S M; Elias, S; Jumiah, H; Asri, M T M; Masrianis, A; Ab Rahman, M Z; Taiman, K; Abdul Rashid, M Y

    2004-05-01

    The radiation-response characteristics of polymetharylic acid gel dosimeter prepared with different concentrations of monomer and cross-linker is described in these studies. The dosimeters were prepared under the hypoxic condition in a glove box and were then irradiated with gamma-rays produced by Co-60 radionuclide that was generated at 1.25MeV energy. The irradiation took place at different doses ranged from 0Gy to 19Gy. Due to the radiation activities, chain-reaction polymerisation processes had taken place in the formation of polymethacrylic acid (PMAA) gel, which cause the dose response mechanism increased in the NMR relaxation rates of protons. It has been observed that for higher concentration of monomer and cross-linker, the polymerization rate was increased. PMID:15468893

  19. Relative radiation sensitivity of the integumentary system: Dose response of the epidermal, microvascular, and dermal populations

    International Nuclear Information System (INIS)

    This presentation lists gross and histologic changes produced by irradiation of the skin that have been quantified. It examines available cell kinetic radiobiological and morphological variables to identify interactions that occur between component populations. The dose response data of the hair and epidermal, fibrocytic, and endothelial cell populations are examined and a rank ordering is attempted. The contribution of the radiosensitivity of these populations to defining the dose tolerance of the skin is discussed. Future clinical needs are considered. The intent is to quantify or define tissue population changes in the irradiated skin so that the data may serve as guidelines to aid the radiation therapist to select therapy schedules that preserve skin function while improving cancer control

  20. SO/sub 2/ dose-response sensitivity classification data for crops and natural vegetation species

    Energy Technology Data Exchange (ETDEWEB)

    Irving, P.M.; Ballou, S.W.

    1980-09-01

    Over the past several years studies have been made on the interaction of sulfur dioxide (SO/sub 2/) and vegetation by performing field research and by developing analytical procedures for applying field observation data to energy impact assessments. As a result of this work, numerous reports have been prepared on crop-pollutant interactions, such as dose-response data; on the applications of such data to screening approaches for identifying crops at risk; and on models that predict crop yield reductions from point source emissions of SO/sub 2/. Data that were used for these studies, such as the crop-at-risk screening procedure, are presented in this report. Maps are also presented that show the national distribution of SO/sub 2/-sensitive crops and natural vegetation.

  1. The effect of biological cohesion on current ripple development

    Science.gov (United States)

    Malarkey, Jonathan; Baas, Jaco H.; Hope, Julie

    2014-05-01

    Results are presented from laboratory experiments examining the role of biological cohesion, associated with Extra Polymeric Substances, on the development of current ripples. The results demonstrate the importance of biological cohesion compared to the effect of physical cohesion associated with clays in an otherwise sandy bed. FURTHER INFORMATION In fluvial and marine environments sediment transport is mainly dependent on the nature of the bed surface (rippled or flat) and the nature of cohesion in the bed. Cohesion can be either physical, as a result of the presence of clays, or biological as a result of the presence of organisms. In the case of the latter, biological cohesion occurs as a result of the presence of Extra Polymeric Substances (EPS) secreted by microorganisms. While it is known that EPS can dramatically increase the threshold of motion (Grant and Gust, 1987), comparatively little is known about the effect of EPS on ripple formation and development. The experiments described here seek to fill this gap. They also allow the effect of biological cohesion to be compared with that of physical cohesion from previous experiments (Baas et al., 2013). The experiments, which were conducted in a 10m flume at Bangor University, involved a current over a bed made of fine sand, with a median diameter of 0.148mm, and various amounts of xanthan gum, a proxy for naturally occurring EPS (Vardy et al., 2007). The hydrodynamic experimental conditions were matched very closely to those of Baas et al. (2013). The ripple dimensions were recorded through the glass side wall of the tank using time lapse photography. In the physical cohesion experiments of Baas et al. (2013) for clay contents up to 12%, the clay was very quickly winnowed out of the bed, leaving essentially clay-free ripples that developed at more or less the same rate as clean sand ripples. The resulting equilibrium ripples were essentially the same length as the clean sand ripples but reduced in height. By

  2. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  3. Radiation dose response correlation between thermoluminescence and optically stimulated luminescence in quartz

    International Nuclear Information System (INIS)

    The fast, linearly modulated optically stimulated luminescence (LM-OSL) component in quartz is the main dosimetric signal used for the dating applications of this material. Since the blue light stimulation (470 nm, 40 mW cm −2) time needed to obtain the fast LM-OSL component is less than 50 s the electron trapping levels responsible for it are still highly populated. In this way an active radiation history is created which could play an important role in the dosimetric characteristics of the fast OSL signal. In the present work the dose response behavior of the fast OSL signal is investigated in quartz samples with an annealed radiation history and quartz samples possessing an artificial radiation history. A computerized curve de-convolution analysis of the LM-OSL curves for 50 s stimulation time showed that it consists of three individual OSL components. The faster component C1 with peak maximum time around 5 s has a linear dose response in virgin samples, which turns to a slight superlinearity as a function of the artificial radiation history. On the other hand the component C2 with peak maximum time at 12 s is slightly superlinear which turns into strong superlinearity as a function of artificial radiation history. Finally, component C3 with peak maximum time at about 45 s is strongly superlinear for both virgin samples and as a function of artificial radiation history. The implications to practical application are discussed. - Highlights: ► The fast OSL component consists of three components. ► The linearity of first fast component does not depend on radiation history. ► The linearity of second and third components depend on radiation history. ► The TL between 180 and 300 °C is the major source of OSL.

  4. Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response

    International Nuclear Information System (INIS)

    Purpose: The purpose of this paper is to use the outcome of a dose escalation protocol for three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer to study the dose-response for late rectal toxicity and to identify anatomic, dosimetric, and clinical factors that correlate with late rectal bleeding in multivariate analysis. Methods and Materials: Seven hundred forty-three patients with T1c-T3 prostate cancer were treated with 3D-CRT with prescribed doses of 64.8 to 81.0 Gy. The 5-year actuarial rate of late rectal toxicity was assessed using Kaplan-Meier statistics. A retrospective dosimetric analysis was performed for patients treated to 70.2 Gy (52 patients) or 75.6 Gy (119 patients) who either exhibited late rectal bleeding (RTOG Grade 2/3) within 30 months after treatment (i.e., 70.2 Gy--13 patients, 75.6 Gy--36 patients) or were nonbleeding for at least 30 months (i.e., 70.2 Gy--39 patients, 75.6 Gy--83 patients). Univariate and multivariate logistic regression was performed to correlate late rectal bleeding with several anatomic, dosimetric, and clinical variables. Results: A dose response for ≥ Grade 2 late rectal toxicity was observed. By multivariate analysis, the following factors were significantly correlated with ≥ Grade 2 late rectal bleeding for patients prescribed 70.2 Gy: 1) enclosure of the outer rectal contour by the 50% isodose on the isocenter slice (i.e., Iso50) (p max (p max

  5. Radiation dose response correlation between thermoluminescence and optically stimulated luminescence in quartz

    Energy Technology Data Exchange (ETDEWEB)

    Oniya, E.O. [Archaeometry Laboratory, Cultural and Educational Technology Institute (C.E.T.I.), R.C. ' Athena' , Tsimiski 58, GR-67100 Xanthi (Greece); Physics and Electronics Department, Adekunle Ajasin University, PMB 01, Akungba Akoko (Nigeria); Polymeris, G.S.; Tsirliganis, N.C. [Archaeometry Laboratory, Cultural and Educational Technology Institute (C.E.T.I.), R.C. ' Athena' , Tsimiski 58, GR-67100 Xanthi (Greece); Kitis, G., E-mail: gkitis@auth.gr [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124 Thessaloniki (Greece)

    2012-07-15

    The fast, linearly modulated optically stimulated luminescence (LM-OSL) component in quartz is the main dosimetric signal used for the dating applications of this material. Since the blue light stimulation (470 nm, 40 mW cm {sup -2}) time needed to obtain the fast LM-OSL component is less than 50 s the electron trapping levels responsible for it are still highly populated. In this way an active radiation history is created which could play an important role in the dosimetric characteristics of the fast OSL signal. In the present work the dose response behavior of the fast OSL signal is investigated in quartz samples with an annealed radiation history and quartz samples possessing an artificial radiation history. A computerized curve de-convolution analysis of the LM-OSL curves for 50 s stimulation time showed that it consists of three individual OSL components. The faster component C{sub 1} with peak maximum time around 5 s has a linear dose response in virgin samples, which turns to a slight superlinearity as a function of the artificial radiation history. On the other hand the component C{sub 2} with peak maximum time at 12 s is slightly superlinear which turns into strong superlinearity as a function of artificial radiation history. Finally, component C{sub 3} with peak maximum time at about 45 s is strongly superlinear for both virgin samples and as a function of artificial radiation history. The implications to practical application are discussed. - Highlights: Black-Right-Pointing-Pointer The fast OSL component consists of three components. Black-Right-Pointing-Pointer The linearity of first fast component does not depend on radiation history. Black-Right-Pointing-Pointer The linearity of second and third components depend on radiation history. Black-Right-Pointing-Pointer The TL between 180 and 300 Degree-Sign C is the major source of OSL.

  6. Airborne trichloramine (NCl(3)) levels and self-reported health symptoms in indoor swimming pool workers: dose-response relationships.

    Science.gov (United States)

    Fantuzzi, Guglielmina; Righi, Elena; Predieri, Guerrino; Giacobazzi, Pierluigi; Petra, Berchotd; Aggazzotti, Gabriella

    2013-01-01

    The hypothesis that attendance at indoor chlorinated swimming pool is a risk factor for irritative ocular and respiratory symptoms and bronchial asthma is well known in literature, although epidemiological evidence is still inconclusive. The aim of this study was to evaluate the association between airborne trichloramine (NCl(3)) levels and irritative symptoms in swimming pool employees in order to obtain detailed data regarding dose-response relationships and to identify the airborne NCl(3) exposure level, if any, without health effects. A total of 20 indoor swimming pools in the Emilia Romagna region of Italy were included in the study. Information about the health status of 128 employees was collected using a self-administered questionnaire. Exposure to airborne NCl(3) was evaluated in indoor swimming pools by a modified DPD/KI method. The results of the study evidenced a mean value of airborne NCl(3) of 0.65±0.20 mg/m(3) (ranging from 0.20 to 1.02 mg/m(3)). Both ocular and upper respiratory symptoms, in particular red eyes, runny nose, voice loss and cold symptoms, were declared more frequently by lifeguards and trainers when compared with employees working in other areas of the facility (office, cafe, and so on). Pool attendants exposed to airborne NCl(3) levels of >0.5 mg/m(3) experienced higher risks for runny nose (OR: 2.91; 95% CI: 1.22-6.93) red eyes (OR: 3.16; 95% CI: 1.46-6.82), voice loss (OR: 3.56; 95% CI: 1.60-7.95) and itchy eyes (OR: 2.23; 95% CI: 1.04-4.78) than other employees. Moreover, red eyes, itchy eyes, runny nose and voice loss are related to airborne NCl(3) levels, with strong dose-response relationships. In conclusion, this study shows that lifeguards and trainers experience ocular and respiratory irritative symptoms more frequently than employees not exposed. Irritative symptoms become significant starting from airborne NCl(3) levels of >0.5 mg/m(3), confirming that the WHO-recommended value can be considered protective in

  7. Red and processed meat consumption and the risk of lung cancer: a dose-response meta-analysis of 33 published studies

    OpenAIRE

    Xue, Xiu-juan; Gao, Qing; Qiao, Jian-Hong; Zhang, Jie; Xu, Cui-Ping; Liu, Ju

    2014-01-01

    This meta-analysis was to summarize the published studies about the association between red/processed meat consumption and the risk of lung cancer. 5 databases were systematically reviewed, and random-effect model was used to pool the study results and to assess dose-response relationships. Results shown that six cohort studies and twenty eight case-control studies were included in this meat-analysis. The pooled Risk Radios (RR) for total red meat and processed meat were 1.44 (95% CI, 1.29-1....

  8. Arsenic at very low concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GR-mediated gene repression: complex dose-response effects are closely correlated with levels of activated GR and require a functional GR DNA binding domain.

    Science.gov (United States)

    Bodwell, Jack E; Kingsley, Lauren A; Hamilton, Joshua W

    2004-08-01

    Arsenic (As) contamination of drinking water is considered a principal environmental health threat throughout the world. Chronic intake is associated with an increased risk of cancer, diabetes, and cardiovascular disease, and recent studies suggest increased health risks at levels as low as 5-10 ppb. We report here that 0.05-1 microM (6-120 ppb) As showed stimulatory effects on glucocorticoid receptor (GR)-mediated gene activation in rat EDR3 hepatoma cells of both the endogenous tyrosine aminotransferase (TAT) gene and the reporter genes containing TAT glucocorticoid response elements. At slightly higher concentrations (1-3 microM), the effects of As became inhibitory. Thus, over this narrow concentration range, the effects of As changed from a 2- to 4-fold stimulation to a greater than 2-fold suppression in activity. Interestingly, the inhibitory effect of GR on both AP1- and NF-kappa B-mediated gene activation was not affected by As. The magnitude of GR stimulation and inhibition by As was highly dependent on the cellular level of hormone-activated GR. Mutational deletion studies indicated that the central DNA binding domain (DBD) of GR is the minimal region required for the As effect and does not require free sulfhydryls. Point mutations located within the DBD that have known structural consequences significantly altered the GR response to As. In particular, point mutations in the DBD that confer a DNA-bound GR confirmation abolished the low dose As stimulatory effect but enhanced the inhibitory response, further indicating that the DBD is important for mediating these As effects. PMID:15310238

  9. Cytogenetic measurements of the relative biological effectiveness of tritium

    International Nuclear Information System (INIS)

    Chromosome aberrations in peripheral blood lymphocytes, which are used to estimate radiation dose biologically, were induced by tritium 1.14 times as effectively as X-rays (95% confidence limits: 0.8 - 1.5). Chromosome translocations in spermatogonia, which are one component of genetic risk, were induced by tritium 1.21 times as effectively as X-rays (95% confidence limits: 0.8 -1.9). All experimental measurements were made in CBA/H mice injected with tritiated water or exposed to X-rays at a comparable dose rate

  10. Biological effects of low level exposures to chemicals and radiation

    International Nuclear Information System (INIS)

    In May 1990 a group of scientists representing several federal agencies, the International Society of Regulatory Toxicology and Pharmacology, the private sector, and academia met to develop a strategy to encourage the study of the biological effects of low level exposures (BELLE) to chemical agents and radioactivity. A workshop was held in 1991 with seven invited speakers focusing on the toxicological implications of biological adaptations. The selection of topics and speakers was designed to consider critically the concept of hormesis, not only in a broad, conceptual manner, but also at the molecular and biochemical levels. These presentations offered a complementary perspective on the diverse range of molecular mechanisms that can become activated at low levels of toxicant exposure. In addition to chemical toxicology research, an overview of current research on 'Effects of low-dose radiation on the immune response' was presented as well as 'Cellular adaptation as an important response during chemical carcinogenesis'. The final presentation was devoted to biostatistical considerations when designing studies that address issues associated with the biological responses to low doses of chemicals and radiation, as well as issues in interpretation of the findings from such studies

  11. Effective biological dose from occupational exposure during nanoparticle synthesis

    International Nuclear Information System (INIS)

    Nanomaterial and nanotechnology safety require the characterization of occupational exposure levels for completing a risk assessment. However, equally important is the estimation of the effective internal dose via lung deposition, transport and clearance mechanisms. An integrated source-to-biological dose assessment study is presented using real monitoring data collected during nanoparticle synthesis. Experimental monitoring data of airborne exposure levels during nanoparticle synthesis of CaSO4 and BiPO4 nanoparticles in a research laboratory is coupled with a human lung transport and deposition model, which solves in an Eulerian framework the general dynamic equation for polydisperse aerosols using particle specific physical-chemical properties. Subsequently, the lung deposition model is coupled with a mathematical particle clearance model providing the effective biological dose as well as the time course of the biological dose build-up after exposure. The results for the example of BiPO4 demonstrate that even short exposures throughout the day can lead to particle doses of 1.10·E+08/(kg-bw·8h-shift), with the majority accumulating in the pulmonary region. Clearance of particles is slow and is not completed within a working shift following a 1 hour exposure. It mostly occurs via macrophage activity in the alveolar region, with small amounts transported to the interstitium and less to the lymph nodes.

  12. Effective biological dose from occupational exposure during nanoparticle synthesis

    Science.gov (United States)

    Demou, Evangelia; Tran, Lang; Housiadas, Christos

    2009-02-01

    Nanomaterial and nanotechnology safety require the characterization of occupational exposure levels for completing a risk assessment. However, equally important is the estimation of the effective internal dose via lung deposition, transport and clearance mechanisms. An integrated source-to-biological dose assessment study is presented using real monitoring data collected during nanoparticle synthesis. Experimental monitoring data of airborne exposure levels during nanoparticle synthesis of CaSO4 and BiPO4 nanoparticles in a research laboratory is coupled with a human lung transport and deposition model, which solves in an Eulerian framework the general dynamic equation for polydisperse aerosols using particle specific physical-chemical properties. Subsequently, the lung deposition model is coupled with a mathematical particle clearance model providing the effective biological dose as well as the time course of the biological dose build-up after exposure. The results for the example of BiPO4 demonstrate that even short exposures throughout the day can lead to particle doses of 1.10·E+08#/(kg-bw·8h-shift), with the majority accumulating in the pulmonary region. Clearance of particles is slow and is not completed within a working shift following a 1 hour exposure. It mostly occurs via macrophage activity in the alveolar region, with small amounts transported to the interstitium and less to the lymph nodes.

  13. Sodium selenite and cancer related lymphedema: Biological and pharmacological effects.

    Science.gov (United States)

    Pfister, Christina; Dawzcynski, Horst; Schingale, Franz-Josef

    2016-09-01

    A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex physical therapy. Pharmacotherapy, for example with diuretics, has received little attention, because they were not effective and only offered short-term solutions. Sodium selenite showed promise as a cost-effective, nontoxic anti-inflammatory agent. Treatment with sodium selenite lowers reactive oxygen species (ROS) production, causes a spontaneous reduction in lymphedema volume, increases the efficacy of physical therapy for lymphedema, and reduces the incidence of erysipelas infections in patients with chronic lymphedema. Besides biological effects in reducing excessive production of ROS, sodium selenite also displays various pharmacological effects. So far the exact mechanisms of these pharmacological effects are mostly unknown, but probably include inhibition of adhesion protein expression. PMID:27267968

  14. Biological effects of pulsating magnetic fields: role of solitons

    CERN Document Server

    Brizhik, Larissa

    2014-01-01

    In this paper, we analyze biological effects produced by magnetic fields in order to elucidate the physical mechanisms, which can produce them. We show that there is a chierarchy of such mechanisms and that the mutual interplay between them can result in the synergetic outcome. In particular, we analyze the biological effects of magnetic fields on soliton mediated charge transport in the redox processes in living organisms. Such solitons are described by nonlinear systems of equations and represent electrons that are self-trapped in alpha-helical polypeptides due to the moderately strong electron-lattice interaction. They represent a particular type of disssipativeless large polarons in low-dimensional systems. We show that the effective mass of solitons in the is different from the mass of free electrons, and that there is a resonant effect of the magnetic fields on the dynamics of solitons, and, hence, on charge transport that accompanies photosynthesis and respiration. These effects can result in non-therm...

  15. The Effects Of Physical And Biological Cohesion On Bedforms

    Science.gov (United States)

    Parsons, D. R.; Schindler, R.; Baas, J.; Hope, J. A.; Malarkey, J.; Paterson, D. M.; Peakall, J.; Manning, A. J.; Ye, L.; Aspden, R.; Alan, D.; Bass, S. J.

    2014-12-01

    Most coastal sediments consist of complex mixtures of cohesionless sands, physically-cohesive clays and extra cellular polymeric substances (EPS) that impart biological cohesion. Yet, our ability to predict bedform dimensions in these substrates is reliant on predictions based exclusively on cohesionless sand. We present findings from the COHBED project - which explicitly examines how bedform dynamics are modified by natural cohesion. Our experimental results show that for ripples, height and length are inversely proportional to initial clay content and bedforms take longer to appear, with no ripples when clay content exceeds 18%. When clay is replaced by EPS the development time and time of first appearance of ripples both increase by two orders of magnitude, with no bedforms above 0.125% EPS. For dunes, height and length are also inversely proportional to initial substrate clay content, resulting in a transition from dunes to ripples normally associated with velocity decreases. Addition of low EPS concentrations into the substrate results in yet smaller bedforms at the same clay contents and at high EPS concentrations, biological cohesion supersedes all electrostatic bonding, and bedform size is no longer related to mud content. The contrast in physical and biological cohesion effects on bedform development result from the disparity between inter-particle electrostatic bonding of clay particles and EPS grain coating and strands that physically link sediments together, which effects winnowing rates as bedforms evolve. These findings have wide ranging implications for bedform predictions in both modern and ancient environments. Coupling of biological and morphological processes not only requires an understanding of how bedform dimensions influence biota and habitat, but also how benthic species can modify bedform dimensions. Consideration of both aspects provides a means in which fluid dynamics, sediment transport and ecosystem energetics can be linked to yield

  16. Study of the dose response of the system ferrous ammonium sulfate–sucrose–xylenol orange in acid aqueous solution

    International Nuclear Information System (INIS)

    An aqueous solution of ammonium ferrous sulfate–sucrose–xylenol orange in sulfuric acid (FSX) is proposed as a dosimetric system for the processes of gamma irradiation in a range between 0.3 and 6 Gy. This system is based on the indirect oxidation of ferrous ion by an organic compound (sucrose) to ferric ion and on the formation of a color complex of Fe3+ in an acidic medium with xylenol orange (a dye). After gamma radiation, an observable change occurs in the color of the system. Irradiation was executed at three different temperatures (13 °C, 22 °C, and 40 °C). A spectrometric readout method at 585 nm was employed to evaluate the system's dose response. In all of the cases analyzed, the responses had a linear behavior, and a slight effect of irradiation temperature was observed. Post-irradiation response was also evaluated and showed the stability of the solutions 24 h after the irradiation. The results obtained suggest that FSX might be used as a dosimeter for low doses of gamma irradiation because it provides a stable signal, good reproducibility, and an accessible technique for analysis. - Highlights: • The system ferrous-sucrose-xylenol is reproducibility with less than 5% error. • The dosimeter has low cost and easy readout using UV-vis spectrometry, and the response is stable for several days. • The system proposed is suitable for low irradiation doses

  17. Statistical issues in radiation dose-response analysis of employees of the nuclear industry in Oak Ridge, Tennessee

    International Nuclear Information System (INIS)

    Poisson regression methods are used to describe dose-response relations for cancer mortality for a subcohort of 28,347 white male radiation workers. Age specific baseline rates are described using both internal and external (US white male) rates. Regression analyses are based on an analytic data structure (ADS) that consists of a table of observed deaths, expected deaths, and person-years at risk for each combination of levels of seven risk factors. The factors are socioeconomic status, length of employment, birth cohort, age at risk, facility, internal exposure, and external exposure. Each observation in the ADS consists of the index value of each of the stratifying factors, the observed deaths, the expected deaths, the person-years, and the ten year lagged average cumulative dose. Regression diagnostics show that a linear exponential relative risk model is not appropriate for these data. Results are presented using a main effects model for factors other than external radiation, and an excess relative risk term for cumulative external radiation dose

  18. A comparison of dose-response characteristics of four NTCP models using outcomes of radiation-induced optic neuropathy and retinopathy

    International Nuclear Information System (INIS)

    Biological models are used to relate the outcome of radiation therapy to dose distribution. As use of biological models in treatment planning expands, uncertainties associated with the use of specific models for predicting outcomes should be understood and quantified. In particular, the question to what extent model predictions are data-driven or dependent on the choice of the model has to be explored. Four dose-response models--logistic, log-logistic, Poisson-based and probit--were tested for their ability and consistency in describing dose-response data for radiation-induced optic neuropathy (RION) and retinopathy (RIRP). Dose to the optic nerves was specified as the minimum dose, Dmin, received by any segment of the organ to which the damage was diagnosed by ophthalmologic evaluation. For retinopathy, the dose to the retina was specified as the highest isodose covering at least 1/3 of the retinal surface (D33%) that geometrically covered the observed retinal damage. Data on both complications were modeled separately for patients treated once daily and twice daily. Model parameters D50 and γ and corresponding confidence intervals were obtained using maximum-likelihood method. Model parameters were reasonably consistent for RION data for patients treated once daily, D50 ranging from 94.2 to 104.7 Gy and γ from 0.88 to 1.41. Similar consistency was seen for RIRP data which span a broad range of complication incidence, with D50 from 72.2 to 75.0 Gy and γ from 1.51 to 2.16 for patients treated twice daily; 72.2-74.0 Gy and 0.84-1.20 for patients treated once daily. However, large variations were observed for RION in patients treated twice daily, D50 from 96.3 to 125.2 Gy and γ from 0.80 to 1.56. Complication incidence in this dataset in any dose group did not exceed 20%. For the considered data sets, the log-logistic model tends to lead to larger D50 and lower γ compared to other models for all datasets. Statements regarding normal tissue radiosensitivity and

  19. Ionol [BHT]. Distribution in the organism, metabolism, and biological effect. II. Biological effects of ionol (survey)

    International Nuclear Information System (INIS)

    In these experiments, a 25 mg/kg dose of ionol, administered to mice immediately after transplantation of melanoma B-16 or injection of tumor cells, inhibited the growth of pigmented B-16 cells and somewhat decreased the number of metastases. Ionol inhibited the mutagenic effect of benz(a)pyrene in vitro and in a culture of Salmonella typhimurium. In a mix with butylhydroxyanisole and propyl gallate, it decreased the number of mutations induced by gamma irradiation in the same culture. It protected mice from dominant lethal mutations and hereditary translocations induced by ethyl methanesulfonate (EMS). When ionol was present in the feed in a dose of 0.75% it reduced the lethal effect in mice of dimethylnitrosamine, EMS, ethylene dibromide and cyclophosphamide

  20. Countermeasures for space radiation induced adverse biologic effects

    Science.gov (United States)

    Kennedy, A. R.; Wan, X. S.

    2011-11-01

    Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

  1. Validation of dose-response curve of CRCN-NE - Regional Center for Nuclear Sciences from Northeast Brazil for {sup 60}Co: preliminary results; Validacao da curva dose-resposta do CRCN-NE para {sup 60}Co: resultados preliminares

    Energy Technology Data Exchange (ETDEWEB)

    Mendonca, Julyanne C.G.; Mendes, Mariana E.; Hwang, Suy F.; Lima, Fabiana F. [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Santos, Neide, E-mail: july_cgm@yahoo.com.br [Universidade Federal de Pernambuco (CCB/UFPE), Recife, PE (Brazil). Departamento de Genetica

    2014-07-01

    The cytogenetic study has the chromosomal alterations as biomarkers in absorbed dose estimation by the body of individuals involved in exposure to ionizing radiation by interpreting a dose response calibration curve. Since the development of the technique to the analysis of data, you can see protocol characteristics, leading the International Atomic Energy Agency indicate that any laboratory with intention to carry out biological dosimetry establish their own calibration curves. The Biological Dosimetry Laboratory of the Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN), Brazil, recently established the calibration curve related to gamma radiation ({sup 60}Co). Thus, this work aimed to start the validation of this calibration curve from samples of three different blood donors which were irradiated with an absorbed known single dose of 1 Gy. Samples were exposed to {sup 60}Co source (Glaucoma 220) located in the Department of Nuclear Energy (DEN/UFPE). After fixation with methanol and acetic acid and 5% Giemsa staining, the frequency of chromosomal alterations (dicentric chromosomes, acentric rings and fragments) were established from reading of 500 metaphases per sample and doses were estimated using Dose Estimate program. The results showed that, using the dose-response curve calibration for dicentrics, the dose absorbed estimated for the three individuals ranged from 0.891 - 1,089Gy, taking into account the range of confidence of 95%. By using the dose-response curve for dicentrics added to rings and for the same interval of confidence the doses ranged from 0,849 - 1,081Gy. Thus, the estimative encompassed known absorbed dose the three individuals in confidence interval of 95%. These preliminary results seems to demonstrate that dicentric dose-response curves and dicentrics plus rings established by CRCN-NE / CNEN are valid for dose estimation in exposed individuals. This validation will continue with samples from different individuals at different doses.

  2. No evident dose-response relationship between cellular ROS level and its cytotoxicity--a paradoxical issue in ROS-based cancer therapy.

    Science.gov (United States)

    Zhu, Chunpeng; Hu, Wei; Wu, Hao; Hu, Xun

    2014-01-01

    Targeting cancer via ROS-based mechanism has been proposed as a radical therapeutic approach. Cancer cells exhibit higher endogenous oxidative stress than normal cells and pharmacological ROS insults via either enhancing ROS production or inhibiting ROS-scavenging activity can selectively kill cancer cells. In this study, we randomly chose 4 cancer cell lines and primary colon or rectal cancer cells from 4 patients to test the hypothesis and obtained following paradoxical results: while piperlongumin (PL) and β-phenylethyl isothiocyanate (PEITC), 2 well-defined ROS-based anticancer agents, induced an increase of cellular ROS and killed effectively the tested cells, lactic acidosis (LA), a common tumor environmental factor that plays multifaceted roles in promoting cancer progression, induced a much higher ROS level in the tested cancer cells than PL and PEITC, but spared them; L-buthionine sulfoximine (L-BSO, 20 μM) depleted cellular GSH more effectively and increased higher ROS level than PL or PEITC but permitted progressive growth of the tested cancer cells. No evident dose-response relationship between cellular ROS level and cytotoxicity was observed. If ROS is the effecter, it should obey the fundamental therapeutic principle - the dose-response relationship. This is a major concern. PMID:24848642

  3. Health and biological effects of non-ionizing radiations

    International Nuclear Information System (INIS)

    This document gathers the slides of the available presentations given during this conference day on the biological and health effects of non-ionizing radiations. Sixteen presentations out of 17 are assembled in the document and deal with: 1 - NMR: biological effects and implications of Directive 2004/40 on electromagnetic fields (S. Lehericy); 2 - impact of RF frequencies from mobile telephone antennas on body homeostasis (A. Pelletier); 3 - expression of stress markers in the brain and blood of rats exposed in-utero to a Wi-Fi signal (I. Lagroye); 4 - people exposure to electromagnetic waves: the challenge of variability and the contribution of statistics to dosimetry (J. Wiart); 5 - status of knowledge about electromagnetic fields hyper-sensitivity (J.P. Marc-Vergnes; 6 - geno-toxicity of UV radiation: respective impact of UVB and UVA (T. Douki); 7 - National day of prevention and screening for skin cancers (F. Guibal); 8 - UV tan devices: status of knowledge about cancer risks (I. Tordjman, and J. Gaillot de Saintignon); 9 - modulation of brain activity during a tapping task after exposure to a 3000 μT magnetic field at 60 Hz (M. Souques and A. Legros); 10 - calculation of ELF electromagnetic fields in the human body by the finite elements method (R. Scoretti); 11 - French population exposure to the 50 Hz magnetic field (I. Magne); 12 - LF and static fields, new ICNIRP recommendations: what has changed, what remains (B. Veyret); 13 - risk assessment of low energy lighting systems - DELs and CFLs (J.P. Cesarini); 14 - biological effects to the rat of a chronic exposure to high power microwaves (R. De Seze); 15 - theoretical and experimental electromagnetic compatibility approaches of active medical implants in the 10-50 Hz frequency range: the case of implantable cardiac defibrillators (J. Katrib); French physicians and electromagnetic fields (M. Souques). (J.S.)

  4. Consequences of dose response curves for tumor control and normal tissue injury on the precision necessary in patient management

    International Nuclear Information System (INIS)

    This paper is concerned with an analysis of the relationship between dose response curves, treatment precision, and treatment outcome. The approach that is taken is first to define the term ''treatment precision'' as it is used in this paper and then to compare the expected treatment outcomes for two treatment systems with different levels of precision. The treatment outcomes will be calculated using assumed dose response curves for tumor control and for severe normal tissue injury. This approach is admittedly theoretical and is not intended to provide any quantitative conclusions concerning the treatment of patients. The approach will, however, provide valuable insight into the relationship between treatment precision and outcome

  5. Patch test dose-response study: polysensitized individuals do not express lower elicitation thresholds than single/double-sensitized individuals

    DEFF Research Database (Denmark)

    Carlsen, B C; Fischer, Louise Arup; Sosted, H;

    2009-01-01

    compare elicitation dose-response curves and elicitation thresholds in a polysensitized vs. a single/double-sensitized group for allergens to which the test subjects were already sensitized. PATIENTS/METHODS: Fifty-one patients (13 polysensitized and 38 single/double-sensitized) were patch tested with...... nickel sulphate, methyldibromo glutaronitrile (MDBGN) and p-phenylenediamine (PPD) in dilution series. The ratio between the doses eliciting a response in 50% of patients in the two groups was used as the measure for relative sensitivity. RESULTS: The dose-response curves of the polysensitized group for...

  6. Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

    DEFF Research Database (Denmark)

    Timar-Gabor, Alida; Constantin, Daniela; Buylaert, Jan-Pieter; Jain, Mayank; Murray, Andrew; Wintle, A.G.

    2015-01-01

    SAR-OSL investigations on quartz from Romanian loess resulted in non concordant fine and coarse-grain ages for equivalent doses higher than ~100 Gy. The laboratory dose response for both grain sizes is well represented by a sum of two saturating exponential functions, fine and coarse grains chara...... equivalent dose of 2000e2500 Gy were found to be below the saturation level of the laboratory dose response curve for both grain sizes; this also applied to the luminescence signals measured after >5000 Gy given on top of natural doses. © 2015 Elsevier Ltd. All rights reserved....

  7. Biological effects of electromagnetic fields; Biologische Wirkungen elektromagnetischer Felder

    Energy Technology Data Exchange (ETDEWEB)

    David, E. [Inst. fuer Physiologie, Univ. Witten-Herdecke (Germany)

    1993-07-26

    In this generally intelligible article, the author describes at first the physical fundamentals of electromagnetic fields and their basic biological significance and effects for animals and human beings before dealing with the discussion regarding limiting values and dangers. The article treats possible connections with leukaemia as well as ith melatonine production more detailed. (vhe) [Deutsch] Der Autor beschreibt in seinem allgemeinverstaendlichen Artikel zuerst die physikalischen Grundlagen elektromagnetischer Felder und ihre grundsaetzliche biologische Bedeutung und Auswirkungen fuer Tiere und Menschen, bevor er auf die Diskussion um Grenzwerte und Gefahren eingeht. Ausfuehrlicher behandelt der Artikel moegliche Zusammenhaenge mit Leukaemie sowie mit der Melatoninproduktion. (vhe)

  8. Hydrodynamic collective effects of active proteins in biological membranes

    CERN Document Server

    Koyano, Yuki; Mikhailov, Alexander S

    2016-01-01

    Lipid bilayers forming biological membranes are known to behave as viscous 2D fluids on submicrometer scales; usually they contain a large number of active protein inclusions. Recently, it has been shown [Proc. Nat. Acad. Sci. USA 112, E3639 (2015)] that such active proteins should in- duce non-thermal fluctuating lipid flows leading to diffusion enhancement and chemotaxis-like drift for passive inclusions in biomembranes. Here, a detailed analytical and numerical investigation of such effects is performed. The attention is focused on the situations when proteins are concentrated within lipid rafts. We demonstrate that passive particles tend to become attracted by active rafts and are accumulated inside them.

  9. Inner-shell ionization and biological radiations effects

    International Nuclear Information System (INIS)

    Biological effects of K-ionizations followed by Auger cascades have been much studied to elucidate mechanisms of cell inactivation and DNA repair and to develop therapeutic applications. Experiments performed with incorporated radionuclides (125I) or incorporated elements (Br, I, P) photoionized in the K-shell using synchrotron radiation all displayed a K + Auger enhancement. The interest in K-ionization rose again when recent works suggested that K-ionizations in C, N, 0 atoms of DNA could be the primary physical events responsible for cell death induced by heavy ions. Photoabsorption experiments at the C-K threshold support this hypothesis. (authors)

  10. [Placebo effect: clinical, biological and therapeutical involvements in depression].

    Science.gov (United States)

    Gourion, D; Mouchabac, S

    2016-02-01

    The placebo effect is an excellent model for understanding the mechanisms underlying the interaction between a subjective and complex mental activity (beliefs, expectations, hopes, learning, patient-physician relationship, socio-cultural context .) with different neural and biological systems. Initially, research on the placebo effect has focused on the mechanisms of pain and analgesia. The cognitive processes of conditioning and reward anticipation (hope of a relief) were highlighted. The involvement of different neurobiological pathways has been clearly shown: endogenous opioids, CCK, dopaminergic pathways, endocannabinoids, immunological factors… More recently, the field has open towards new perspectives: depression and anxiety, motor disorders, immune system, endocrine system. Intensive research in the field emerges because of its fundamental implications in neuroscience research but also because of the ethical, clinical and therapeutical issues. Moreover, the placebo effect is considered as a main methodological mean issue in clinical trials that allows the demonstration of the efficacy and tolerance of new drugs. In the field of psychiatry, depression is a placebo highly-sensitive disorder: placebo response rates in clinical trials are of the order of 30 % to 40 %. The identification of biological markers of placebo response, such as neuroimaging and quantitative electroencephalography may lead to develop more efficient models in clinical research. PMID:26879253

  11. Spatial interpolation of biologically effective UV radiation over Poland

    Science.gov (United States)

    Walawender, J.; Ustrnul, Z.

    2010-09-01

    The ultraviolet(UV) radiation plays an important role in the Earth-Atmosphere System. It has a positive influence on both human health and natural environment but it may also be very harmful if UV exposure exceeds "safe" limits. For that reason knowledge about spatial distribution of biologically effective UV doses seems to be crucial in minimization or complete elimination of the negative UV effects. The main purpose of this study is to find the most appropriate interpolation method in order to create reliable maps of the biologically effective UV radiation over Poland. As the broadband UV measurement network in Poland is very sparse, erythemaly weighted UV radiation data reconstructed from homogeneous global solar radiation records were used. UV reconstruction model was developed in Centre of Aerology (Institute of Meteorology and Water Management) within COST Action 726 - ‘Long term changes and climatology of UV radiation over Europe'. The model made it possible to reconstruct daily erythemal UV doses for 21 solar radiation measurement stations in the period 1985 - 2008. Mapping methodology included the following processing steps: exploratory spatial data analysis, verification of additional variables, selection and parameterization of interpolation model, accuracy assessment and cartographic visualization. Several different stochastic and deterministic interpolation methods along with various empirical semivariogram models were tested. Multiple regression analysis was performed in order to examine statistical relationship between UV radiation and additional environmental variables such as: elevation, latitude, stratospheric ozone content and cloud cover. The data were integrated, processed and visualized within GIS environment.

  12. Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

    Directory of Open Access Journals (Sweden)

    Swann Alan C

    2006-01-01

    MPD-induced attenuation were also found among these brain areas. Conclusion These results suggest that an acute treatment of MPD produces electrophysiologically detectable alterations at the neuronal level, as well as observable, behavioral responses. The present study is the first to investigate the acute dose-response effects of MPD on behavior in terms of locomotor activity and in the brain involving the sensory inputs of VTA, NAc, and PFC neurons in intact, non-anesthetized, freely behaving rats previously implanted with permanent electrodes.

  13. Effects of industrial chemicals and radioactive materials in biological systems

    International Nuclear Information System (INIS)

    Much has been written on the effects of radiation and toxic chemicals on biological systems. In this communication general considerations regarding these topics will be discussed very briefly; the major emphasis will be focused on the effects of chemicals, namely ethyl methane sulfonate (EMS) on Amoeba, Advantages to the use of amoeba for studying the effects of radiation and chemicals include the following: large mononucleate unicellular organisms having a long generation time; opportunity to study cellular organelles and biochemical and genetic alterations in a single cell system; and a long cell cycle, the stages of which can be synchronized without resorting to chemical treatment or temperature shock and thereby readily permitting study at defined stages of the cell's life cycle. This, in turn, is discussed in light of current disposal methods for this type of waste and how it might be safely disposed of

  14. Linearization of dose-response curve of the radiochromic film dosimetry system

    Energy Technology Data Exchange (ETDEWEB)

    Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad; DeBlois, Francois; Seuntjens, Jan; Chan, Maria F.; Lewis, Dave [Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Executive Administration for Radiation Protection and Safety Medical Devices Sector, Saudi Food and Drug Authority, Riyadh, Kingdom of Saudi Arabia 13312 (Saudi Arabia); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center Basking Ridge, New Jersey 07920 (United States); Ashland Inc., Wayne, New Jersey 07470 (United States)

    2012-08-15

    Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also

  15. A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Lemos-Pinto, M.M.P.; Cadena, M.; Santos, N.; Fernandes, T.S.; Borges, E.; Amaral, A., E-mail: marcelazoo@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear

    2015-10-15

    Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates. (author)

  16. Multistage models of carcinogenesis and their implications for dose-response models and risk projections

    International Nuclear Information System (INIS)

    Multistage models are used to both describe the biological steps in developing a cancer and as a mathematical description of the relationship of exposure to tumor incidence. With the rapid development of molecular biology the stages of tumor development are becoming understood. Specifically, the effect and role of proto-oncogenes and suppressor genes are exciting developments in the field of carcinogenesis. Mathematically the field has moved from the original Armitage-Doll multistage model to the more current cell kinetic models. These latter models attempt to describe both the rate of cell mutation and the birth-death process involved in clonal expansion. This then allows modeling of both initiation and promotion or cellular proliferation. The field of radiation carcinogenesis has a considerable body of data and knowledge. Unfortunately, relatively little work has been done with the cell kinetic models as to estimation of tumor incidence. This may be due to the newness of kinetic models in general. The field holds promise and it is essential if we are to develop better human risk estimates from exposure to ionizing radiation. (author)

  17. A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

    International Nuclear Information System (INIS)

    Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates. (author)

  18. The biological effects of radium-224 injected into dogs

    International Nuclear Information System (INIS)

    A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected 224Ra chloride. The 224Ra chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of 224Ra resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of 224Ra kg-1 body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected 224Ra (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected 224Ra was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed α-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of 224Ra and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. 52 refs., 8 figs., 8 tabs

  19. Hafnium oxide nanoparticles: toward an in vitro predictive biological effect?

    International Nuclear Information System (INIS)

    Hafnium oxide, NBTXR3 nanoparticles were designed for high dose energy deposition within cancer cells when exposed to ionizing radiation. The purpose of this study was to assess the possibility of predicting in vitro the biological effect of NBTXR3 nanoparticles when exposed to ionizing radiation. Cellular uptake of NBTXR3 nanoparticles was assessed in a panel of human cancer cell lines (radioresistant and radiosensitive) by transmission electron microscopy. The radioenhancement of NBTXR3 nanoparticles was measured by the clonogenic survival assay. NBTXR3 nanoparticles were taken up by cells in a concentration dependent manner, forming clusters in the cytoplasm. Differential nanoparticle uptake was observed between epithelial and mesenchymal or glioblastoma cell lines. The dose enhancement factor increased with increase NBTXR3 nanoparticle concentration and radiation dose. Beyond a minimum number of clusters per cell, the radioenhancement of NBTXR3 nanoparticles could be estimated from the radiation dose delivered and the radiosensitivity of the cancer cell lines. Our preliminary results suggest a predictable in vitro biological effect of NBTXR3 nanoparticles exposed to ionizing radiation

  20. Biological effect of carbon beams on cultured human cells

    International Nuclear Information System (INIS)

    This study was performed to determine the biological effect of carbon beams on 13 human tumor cells, in comparison with 200 KVp X-rays. Carbon beams were generated by the Riken Ring Cyclotron. The RBE (relative biological effectiveness) values were distributed from 1.46 to 2.20 for LET of 20 keV/μm, and 2.29-3.54 for 80 keV/μm. The RBEs were increased in all cell lines as the LET of carbon beams was increased from 20 to 80 keV/μm. There was no significant difference in radiosensitivity between cells from adenocarcinoma and those from squamous cell carcinoma. The relationship between the radiosensitivity of cells to X-rays and RBE was analyzed, but no significant correlation was suggested. Several survival curves of 20-40 keV/μm carbon beam irradiation showed the initial shoulders and the recovery ratios between two split doses were determined. Recovery was observed for LET of 2O keV/μm but not for that of 40 keV/μm. Furthermore, recovery ratios were 1.0-1.8, smaller than those for X-rays (1.5-2.4). (author)