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Sample records for dose response studies

  1. Patch test dose-response study of p-phenylenediamine

    DEFF Research Database (Denmark)

    Sosted, Heidi; Menné, Torkil; Johansen, Jeanne Duus

    2006-01-01

    The elicitation response in allergic contact dermatitis for the hair dye substance p-phenylenediamine (PPD) is dose dependent, but threshold concentrations have not previously been investigated. 15 PPD-sensitive patients participated in a serial dilution 48-hr patch test with PPD using 8...... concentrations of PPD ranging from 1 to 10 000 on the upper back. Petrolatum was applied as control. Three concentrations (50, 100 and 500 p.p.m. PPD) were also applied to the retroauricular area and on the lateral aspects of the upper arms. 14 of the 15 participants reacted to one or more of the test samples....... The threshold value for 10% of the tested persons (ED10) based on+or stronger reactions for PPD on the back was 38 p.p.m. (CI: 4.3-100). There were no statistically significant differences in the sensitivity of the three anatomical regions. The upper back is a suitable region for patch testing patients...

  2. Patch test dose-response study of p-phenylenediamine

    DEFF Research Database (Denmark)

    Sosted, Heidi; Menné, Torkil; Johansen, Jeanne Duus

    2006-01-01

    . The threshold value for 10% of the tested persons (ED10) based on+or stronger reactions for PPD on the back was 38 p.p.m. (CI: 4.3-100). There were no statistically significant differences in the sensitivity of the three anatomical regions. The upper back is a suitable region for patch testing patients......The elicitation response in allergic contact dermatitis for the hair dye substance p-phenylenediamine (PPD) is dose dependent, but threshold concentrations have not previously been investigated. 15 PPD-sensitive patients participated in a serial dilution 48-hr patch test with PPD using 8...... concentrations of PPD ranging from 1 to 10 000 on the upper back. Petrolatum was applied as control. Three concentrations (50, 100 and 500 p.p.m. PPD) were also applied to the retroauricular area and on the lateral aspects of the upper arms. 14 of the 15 participants reacted to one or more of the test samples...

  3. A DoseResponse Study of Magnesium Sulfate in Suppressing Cardiovascular Responses to Laryngoscopy & Endotracheal Intubation

    Directory of Open Access Journals (Sweden)

    K Montazeri

    2005-03-01

    Full Text Available Background: The effects of pretreatment with magnesium on cardiovascular responses associated with intubation have been studied previously. In this study we wanted to find optimal dose of magnesium that causes decreased cardiovascular responses after laryngoscopy & endotracheal intubation. Methods: In a double-blind , randomized, clinical trial ,120 ASA-1 patients with ages between 15-50 years old , who were candidates for elective surgery, were selected and classified in 6 groups (20 patients in each . The pulse rate and arterial blood pressure were measured and recorded at 5 minutes before taking any drug then, according to different groups, patients took magnesium sulfate (10, 20, 30, 40, 50mg/kg and lidocaine (1.5 mg/kg. The induction of anesthesia was same in all groups and the pulse rate and arterial blood pressure were measured and recorded just before intubation and also at 1, 3 , and 5 minutes after intubation (before surgical incision . Statistical analysis was performed by use of ANOVA, Post Hoc test (Duncan, Pearson correlation, and Chi square test. Results: there were no statistically significant differences in blood pressure, pulse rate, Train Of Four (TOF, and complications between groups who received magnesium but the significant differences in these parameters were seen between magnesium and lidocaine groups. Conclusion: We concluded that pretreatment with different doses of magnesium sulfate have a safe decreasing effect on cardiovascular responses that is more effective than pretreatment with lidocaine. Keywords: magnesium sulfate, cardiovascular responses, lidocaine.

  4. PACAP38 dose-response pilot study in migraine patients

    DEFF Research Database (Denmark)

    Vollesen, Anne Luise Haulund; Guo, Song; Ashina, Messoud

    2017-01-01

    Background Intravenous infusion of 10 pmol/kg/min pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces migraine-like attacks in migraine patients without aura (MO). Here, we conducted a pilot study and investigated if lower doses of PACAP38 exert similar migraine......-inducing abilities. Methods We randomly allocated six MO patients to receive intravenous infusion of 4, 6, and 8 pmol/kg/min of PACAP38 over 20 minutes in a double-blind, three-way cross-over study. Headache and migraine characteristics were recorded during hospital (0-2 hours) and post-hospital (2-13 hours) phases....... Results PACAP38 induced migraine-like attacks in one out of six patients with 4 pmol, two out of six patients with 6 pmol and three out of six patients with 8 pmol ( p = 0.368). All patients reported head pain after 8 pmol/kg/min, whereas five of six participants reported head pain after both 4 and 6 pmol...

  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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Optimal experimental designs for dose-response studies with continuous endpoints.

    Science.gov (United States)

    Holland-Letz, Tim; Kopp-Schneider, Annette

    2015-11-01

    In most areas of clinical and preclinical research, the required sample size determines the costs and effort for any project, and thus, optimizing sample size is of primary importance. An experimental design of dose-response studies is determined by the number and choice of dose levels as well as the allocation of sample size to each level. The experimental design of toxicological studies tends to be motivated by convention. Statistical optimal design theory, however, allows the setting of experimental conditions (dose levels, measurement times, etc.) in a way which minimizes the number of required measurements and subjects to obtain the desired precision of the results. While the general theory is well established, the mathematical complexity of the problem so far prevents widespread use of these techniques in practical studies. The paper explains the concepts of statistical optimal design theory with a minimum of mathematical terminology and uses these concepts to generate concrete usable D-optimal experimental designs for dose-response studies on the basis of three common dose-response functions in toxicology: log-logistic, log-normal and Weibull functions with four parameters each. The resulting designs usually require control plus only three dose levels and are quite intuitively plausible. The optimal designs are compared to traditional designs such as the typical setup of cytotoxicity studies for 96-well plates. As the optimal design depends on prior estimates of the dose-response function parameters, it is shown what loss of efficiency occurs if the parameters for design determination are misspecified, and how Bayes optimal designs can improve the situation.

  7. Elicitation threshold of cobalt chloride: analysis of patch test dose-response studies.

    Science.gov (United States)

    Fischer, Louise A; Johansen, Jeanne D; Voelund, Aage; Lidén, Carola; Julander, Anneli; Midander, Klara; Menné, Torkil; Thyssen, Jacob P

    2016-02-01

    Cobalt is a strong skin sensitizer (grade 5 of 5 in the guinea-pig maximization test) that is used in various industrial and consumer applications. To prevent sensitization to cobalt and elicitation of allergic cobalt dermatitis, information about the elicitation threshold level of cobalt is important. To identify the dermatitis elicitation threshold levels in cobalt-allergic individuals. Published patch test dose-response studies were reviewed to determine the elicitation dose (ED) levels in dermatitis patients with a previous positive patch test reaction to cobalt. A logistic dose-response model was applied to data collected from the published literature to estimate ED values. The 95% confidence interval (CI) for the ratio of mean doses that can elicit a reaction in 10% (ED(10)) of a population was calculated with Fieller's method. On the basis of five included studies, the ED10 values of aqueous cobalt chloride ranged between 0.0663 and 1.95 µg cobalt/cm(2), corresponding to 30.8-259 ppm. Our analysis provides an overview of the doses of cobalt that are required to elicit allergic cobalt contactdermatitis in sensitized individuals, and thereby the basis for future prevention of cobalt allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. 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.

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

    DEFF Research Database (Denmark)

    Christiansen, Erik; Goldney, R; Beautrai, A

    2011-01-01

    BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suic...

  10. Dose-response relationship in clinical oncology

    International Nuclear Information System (INIS)

    Gehan, E.A.

    1984-01-01

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

  11. A study of dose-response relationship between tobacco habits and oral leukoplakia.

    OpenAIRE

    Gupta, P. C.

    1984-01-01

    In a house-to-house survey in Ernakulam district, Kerala, India, 12,213 tobacco users were interviewed about the details of their tobacco usage and examined for the presence of leukoplakia. The frequency of tobacco habit was associated with the prevalence of leukoplakia indicating a positive dose-response relationship. The dose-response relationship remained significant, taking age, sex, and the type of tobacco habit into account. After adjusting for all these variables jointly the associatio...

  12. Dose-response study of thimerosal-induced murine systemic autoimmunity

    International Nuclear Information System (INIS)

    Havarinasab, S.; Lambertsson, L.; Qvarnstroem, J.; Hultman, P.

    2004-01-01

    The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury. A.SW mice were exposed to 1.25-40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 μg Hg/kg bw and a concentration of 21 and 1.9 μg Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose-response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury

  13. Dose-Response Relation Between Work Hours and Cardiovascular Disease Risk: Findings From the Panel Study of Income Dynamics.

    Science.gov (United States)

    Conway, Sadie H; Pompeii, Lisa A; Roberts, Robert E; Follis, Jack L; Gimeno, David

    2016-03-01

    The aim of this study was to examine the presence of a dose-response relationship between work hours and incident cardiovascular disease (CVD) in a representative sample of U.S. workers. A retrospective cohort study of 1926 individuals from the Panel Study of Income Dynamics (1986 to 2011) employed for at least 10 years. Restricted cubic spline regression was used to estimate the dose-response relationship of work hours with CVD. A dose-response relationship was observed in which an average workweek of 46 hours or more for at least 10 years was associated with an increased risk of CVD. Compared with working 45 hours per week, working an additional 10 hours per week or more for at least 10 years increased CVD risk by at least 16%. Working more than 45 work hours per week for at least 10 years may be an independent risk factor for CVD.

  14. Effect of almond consumption on the serum fatty acid profile: a dose-response study.

    Science.gov (United States)

    Nishi, Stephanie; Kendall, Cyril W C; Gascoyne, Ana-Maria; Bazinet, Richard P; Bashyam, Balachandran; Lapsley, Karen G; Augustin, Livia S A; Sievenpiper, John L; Jenkins, David J A

    2014-10-14

    Consumption of almonds has been shown to be associated with a decreased risk of CHD, which may be related to their fatty acid (FA) composition. However, the effect of almond consumption on the serum FA composition is not known. Therefore, in the present study, we investigated whether almond consumption would alter the serum FA profile and risk of CHD, as calculated using Framingham's 10-year risk score, in a dose-dependent manner in hyperlipidaemic individuals when compared with a higher-carbohydrate control group using dietary interventions incorporating almonds. A total of twenty-seven hyperlipidaemic individuals consumed three isoenergetic (mean 1770 kJ/d) supplements during three 1-month dietary phases: (1) full-dose almonds (50-100 g/d); (2) half-dose almonds with half-dose muffins; (3) full-dose muffins. Fasting blood samples were obtained at weeks 0 and 4 for the determination of FA concentrations. Almond intake (g/d) was found to be inversely associated with the estimated Framingham 10-year CHD risk score (P= 0·026). In both the half-dose and full-dose almond groups, the proportions of oleic acid (OA) and MUFA in the TAG fraction (half-almond: OA P= 0·003; MUFA P= 0·004; full-almond: OA Pconsumption increases OA and MUFA content in serum TAG and NEFA fractions, which are inversely associated with CHD lipid risk factors and overall estimated 10-year CHD risk.

  15. Long-term dose-response studies of inhaled or injected radionuclides

    International Nuclear Information System (INIS)

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques

  16. Coffee Intake Decreases Risk of Postmenopausal Breast Cancer: A Dose-Response Meta-Analysis on Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Alessandra Lafranconi

    2018-01-01

    Full Text Available Aim: A dose-response meta-analysis was conducted in order to summarize the evidence from prospective cohort studies regarding the association between coffee intake and breast cancer risk. Methods: A systematic search was performed in electronic databases up to March 2017 to identify relevant studies; risk estimates were retrieved from the studies and linear and non-linear dose-response analysis modelled by restricted cubic splines was conducted. A stratified and subgroup analysis by menopausal and estrogen/progesterone receptor (ER/PR status, smoking status and body mass index (BMI were performed in order to detect potential confounders. Results: A total of 21 prospective studies were selected either for dose-response, the highest versus lowest category of consumption or subgroup analysis. The dose-response analysis of 13 prospective studies showed no significant association between coffee consumption and breast cancer risk in the non-linear model. However, an inverse relationship has been found when the analysis was restricted to post-menopausal women. Consumption of four cups of coffee per day was associated with a 10% reduction in postmenopausal cancer risk (relative risk, RR 0.90; 95% confidence interval, CI 0.82 to 0.99. Subgroup analyses showed consistent results for all potential confounding factors examined. Conclusions: Findings from this meta-analysis may support the hypothesis that coffee consumption is associated with decreased risk of postmenopausal breast cancer.

  17. Dose response relationship and Alara

    International Nuclear Information System (INIS)

    Hubert, P.

    1986-09-01

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

  18. Immune response in infants after universal high-dose hepatitis B vaccination: A community-based study in Beijing, China.

    Science.gov (United States)

    Xiao, Min; Qiu, Qian; Pang, Xinghuo; Liang, Xiaofeng; Li, Li; Cui, Fuqiang; Wang, Fuzhen; Zhang, Guomin; Li, Hui; Wang, Li; Zhang, Wei

    2015-10-26

    Vaccination of infants beginning at birth is recommended to prevent Hepatitis B virus (HBV) infection in China. Compared to 5 μg/dose vaccine administered in other regions in China, a three-dose HB recombinant yeast vaccine at 10 μg/dose has been administered for infants within 24h after birth, 1 month and 6 months of age in Beijing since 2006. In a community-based retrospective cohort study, factors influencing immunologic vaccine response were evaluated. A total of 3670 infants who completed a 3-dose 10 μg recombinant HB vaccine regimen and born to hepatitis B antigen negative mothers were included. The effect on anti-HBs titers of maternal nutrient status, infants' birth condition, growth factors, timeliness of vaccination, dosing interval and the interval until post-vaccination serologic testing (PVST) were evaluated. A total of 3666 infants with no markers of HBV infection were included in analysis. The mean anti-HB titers were 1767.17 mIU/ml. Only 16.9% of the infants completed their PVST within 30-59 days after the final dose of vaccination. Multivariate linear regression analysis showed that delay in PVST (β=-0.097, panti-HB titers. Also a trend toward significant association was observed between the calcium supplementation of infants and log-transformed anti-HBs titers (β=0.062, p=0.057). Longer interval between dose 2 and dose 3 was not observed to increase the anti-HB titers after cofactors adjustment. Our findings illustrate the importance of timing of PVST to avoid unnecessary revaccination. Multi-center large cohort studies should verify the effect and magnitude of folate and calcium supplementation on HB vaccine response. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects.

    Science.gov (United States)

    Strassman, R J; Qualls, C R

    1994-02-01

    To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo-controlled, randomized design. Treatments were separated by at least 1 week. Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures. Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.

  20. Study of response of radiation monitors for environmental dose equivalent measurements

    International Nuclear Information System (INIS)

    Souza, Macilene N.; Khoury, H.J.

    2005-01-01

    The environmental dose equivalent H * (10), is the magnitude recommended by ICRU 39 for environmental monitoring in fields of radiation of photons. Most of the equipment used for area monitoring, only quantifies the magnitudes exposure or dose not being designed to this new magnitude. In Brazil, particularly, is not yet regulated the use of H * (10). However, with the revision of the standard 3.01 it will necessary the use of monitors that allow the achievement of measures according to H * (10). The transition for using new magnitudes will be a slow process and the contribution that the laboratories of metrology of ionizing radiation in the country can give is, at first, promote and create the habit of using the unit Sievert (Sv) in the calibration of the instruments, and that is the unit recommended for H * (10). In a second step, the tests for determining the response of the instruments for H * (10) should be made and this is the harder step, taking into account the large number of area monitors around the country. These tests will provide information about the limitations of the instrument to the new magnitude, that is, the range where the instrument will have the best performance in quantification of new magnitude. This paper evaluates the performance for H * (10), with the variation of energy and angle of incidence of radiation, of three of the most used monitors in the country

  1. Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies.

    Science.gov (United States)

    Hu, Kejia; Callen, David Frederick; Li, Jiayuan; Zheng, Hong

    2017-05-01

    Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients' vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), P for linear trend response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.

  2. Influence of Exercise Intensity for Improving Depressed Mood in Depression: A Dose-Response Study.

    Science.gov (United States)

    Meyer, Jacob D; Koltyn, Kelli F; Stegner, Aaron J; Kim, Jee-Seon; Cook, Dane B

    2016-07-01

    Exercise effectively improves mood in major depressive disorder (MDD), but the optimal exercise stimulus to improve depressed mood is unknown. To determine the dose-response relationship of acute exercise intensity with depressed mood responses to exercise in MDD. We hypothesized that the acute response to exercise would differ between light, moderate, and hard intensity exercise with higher intensities yielding more beneficial responses. Once weekly, 24 women (age: 38.6±14.0) diagnosed with MDD underwent a 30-minute session at one of three steady-state exercise intensities (light, moderate, hard; rating of perceived exertion 11, 13 or 15) or quiet rest on a stationary bicycle. Depressed mood was evaluated with the Profile of Mood States before, 10 and 30 minutes post-exercise. Exercise reduced depressed mood 10 and 30 minutes following exercise, but this effect was not influenced by exercise intensity. Participants not currently taking antidepressants (n=10) had higher baseline depression scores, but did not demonstrate a different antidepressant response to exercise compared to those taking antidepressants. To acutely improve depressed mood, exercise of any intensity significantly improved feelings of depression with no differential effect following light, moderate, or hard exercise. Pharmacological antidepressant usage did not limit the mood-enhancing effect of acute exercise. Acute exercise should be used as a symptom management tool to improve mood in depression, with even light exercise an effective recommendation. These results need to be replicated and extended to other components of exercise prescription (e.g., duration, frequency, mode) to optimize exercise guidelines for improving depression. Copyright © 2016. Published by Elsevier Ltd.

  3. Effect of preoperative pregabalin on post-caesarean delivery analgesia: a dose-response study.

    Science.gov (United States)

    El Kenany, S; El Tahan, M R

    2016-05-01

    We hypothesised that preoperative administration of a single-dose of pregabalin would be associated with lower morphine consumption after uncomplicated caesarean delivery. After Institutional Ethics Committee approval, 135 parturients scheduled for elective caesarean delivery under spinal anaesthesia were randomly allocated to receive either placebo, or oral pregabalin 150mg or 300mg, one hour before induction of anaesthesia. Maternal cumulative morphine requirement at 24h, pain scores, sedation scores, nausea and vomiting, pruritus, pregabalin-related adverse effects, Apgar scores, Neurologic and Adaptive Capacity scores and umbilical cord acid-base status were recorded. Compared with placebo or pregabalin 150mg, the use of a preoperative dose of pregabalin 300mg resulted in significantly lower cumulative morphine consumption at 24h (mean dose: placebo 12.9mg [95% CI 11.6 to 14.2]; pregabalin 150mg 11.9mg; [95% CI 10.7 to 13.1]; pregabalin 300mg 6mg [95% CI 5.4 to 7.3]; Ppain scores at 4h and 6h after delivery (Pumbilical cord acid-base status. Three babies in the pregabalin 300mg group (6.7%) experienced short-term poor latching-on for breastfeeding. In our study, preoperative administration of pregabalin 300mg reduced postoperative morphine consumption and early postoperative pain in parturients undergoing elective caesarean delivery, although maternal side effects were more common. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Low Dose Studies with Focused X-rays in Cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    Energy Technology Data Exchange (ETDEWEB)

    Barry D. Michael; Kathryn Held; Kevin Prise

    2002-12-19

    study the biological basis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and there it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  5. Dose response relationship at low doses

    International Nuclear Information System (INIS)

    Schull, W.J.

    1992-01-01

    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

  6. Developing guidelines for economic evaluation of environmental impacts in EIAs. Part II: Case studies and dose-response literature

    International Nuclear Information System (INIS)

    2005-01-01

    This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6

  7. Light exposure at night, sleep duration, melatonin, and breast cancer: a dose-response analysis of observational studies.

    Science.gov (United States)

    Yang, Wan-Shui; Deng, Qin; Fan, Wen-Yan; Wang, Wei-Ye; Wang, Xin

    2014-07-01

    Evidence from observational studies on light at night (LAN) exposure, sleep duration, endogenous melatonin levels, and risk for breast cancer in women is conflicting. This led us to conduct a dose-response analysis of published observational data. Pertinent studies were identified by searching Medline, Web of Science, and EMBASE through April 2013. The dose-response relationship between sleep duration, urinary 6-sulphatoxymelatonin levels, and breast cancer was assessed using the restricted cubic spline model and by multivariate random-effects metaregression. A separate meta-analysis was also carried out to calculate the relative risks (RRs) with 95% confidence intervals (CIs) for breast cancer for the comparable categories or highest levels of exposure versus the lowest levels. Twelve case-control and four cohort studies were included in the analysis. High artificial LAN exposure is associated with an increased risk for breast cancer (RR=1.17, 95% CI: 1.11-1.23), but not ambient LAN exposure (RR=0.91, 95% CI: 0.78-1.07). The summary RR for breast cancer is 1.00 (95% CI: 0.995-1.01) for an increment of 1 h of sleep per night. No significant dose-response relationship between sleep duration and breast cancer was found either for the linearity test (Ptrend=0.725) or for the nonlinearity (Ptrend=0.091) test. An increasein of 15 ng/mg creatinine in urinary 6-sulphatoxymelatonin is associated with a 14% reduced risk for breast cancer (RR=0.86, 95% CI: 0.78-0.95), with a linear dose-response trend (Ptrend=0.003). There was no evidence of substantial heterogeneity or publication bias in the analysis. Our study adds to the evidence of LAN breast cancer theory. Further research in this area is warranted.

  8. Developing guidelines for economic evaluation of environmental impacts in EIAs. Part II: Case studies and dose-response literature

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6.

  9. Digitoxin medication and cancer; case control and internal dose-response studies

    International Nuclear Information System (INIS)

    Haux, Johan; Klepp, Olbjørn; Spigset, Olav; Tretli, Steinar

    2001-01-01

    Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents

  10. Depressive disorder, coronary heart disease, and stroke: dose-response and reverse causation effects in the Whitehall II cohort study.

    Science.gov (United States)

    Brunner, Eric J; Shipley, Martin J; Britton, Annie R; Stansfeld, Stephen A; Heuschmann, Peter U; Rudd, Anthony G; Wolfe, Charles D A; Singh-Manoux, Archana; Kivimaki, Mika

    2014-03-01

    Systematic reviews examining associations of depressive disorder with coronary heart disease and stroke produce mixed results. Failure to consider reverse causation and dose-response patterns may have caused inconsistencies in evidence. This prospective cohort study on depressive disorder, coronary heart disease, and stroke analysed reverse causation and dose-response effects using four 5-year and three 10-year observation cycles (total follow up 24 years) based on multiple repeat measures of exposure. Participants in the Whitehall II study (n = 10,036, 31,395 person-observations, age at start 44.4 years) provided up to six repeat measures of depressive symptoms via the 30-item General Health Questionnaire (GHQ-30) and one measure via Center for Epidemiologic Studies Depression Scale (CES-D). The cohort was followed up for major coronary events (coronary death/nonfatal myocardial infarction) and stroke (stroke death/morbidity) through the national mortality register Hospital Episode Statistics, ECG-screening, medical records, and self-report questionnaires. GHQ-30 caseness predicted stroke over 0-5 years (age-, sex- and ethnicity-adjusted HR 1.60, 95% CI 1.1-2.3) but not over 5-10 years (HR 0.94, 95% CI 0.6-1.4). Using the last 5-year observation cycle, cumulative GHQ-30 caseness was associated with incident coronary heart disease in a dose-response manner (1-2 times a case: HR 1.12, 95% CI 0.7-1.7; 3-4 times: HR 2.06, 95% CI 1.2-3.7), and CES-D caseness predicted coronary heart disease (HR 1.81, 95% CI 1.1-3.1). There was evidence of a dose-response effect of depressive symptoms on risk of coronary heart disease. In contrast, prospective associations of depressive symptoms with stroke appeared to arise wholly or partly through reverse causation.

  11. Response to low-dose intrathecal clonidine in septuagenarians undergoing sub-umbilical surgeries: A study

    Directory of Open Access Journals (Sweden)

    Jayashree Sen

    2015-01-01

    Full Text Available Clonidine, an alpha-2-adrenergic agonist, may have a clinically relevant analgesic action but also a hypotensive action, when administered spinally. Aim: To evaluate the analgesic and circulatory effects of low-dose intrathecal clonidine co-administered with hyperbaric bupivacaine in septuagenarian patients undergoing sub-umbilical surgeries. Materials and Methods: A total of 20 patients within the age group of 70-80 years of either sex, enrolled in this study, were randomly divided into groups of 10 each. Group I received clonidine 7.5 μg as an adjuvant to 15 mg of hyperbaric bupivacaine and Group II (control group received 15 mg of bupivacaine with saline to make volume in the two solutions equal. Result: The level of subarachnoid block was comparable in the two groups. Duration of motor blockade was longer in the clonidine group (221.4 ± 35.92 min compared with the control group (112.3 ± 12.45 min. Request for 1 st dose of analgesic was earlier in the control group (135.5 ± 28.52 min than the clonidine group (295 ± 18.85 min. Mean arterial pressure (clonidine 77.67 ± 6.47 vs. control 93.87 ± 3.03, P = 0.0002 and heart rate (clonidine 65.2 ± 5.20 vs. control 77.4 ± 6.06, P = 0.003 were significantly lower (P < 0.05 in the clonidine group compared with the control group from 20 mins after the block to the end of 3 h. In the clonidine group, 3 patients had postoperative headache, 4 had intra-operative shivering. 2 patients in the clonidine group also developed hypotension and 1 bradycardia and 1 of them developed bradyapnea along with acute hypotension 5 min after shifting to the postoperative ward and later recovered on resuscitation. In the control group 2 patients had bradycardia, 6 had intra-operative shivering and 3 had postoperative headache. Conclusion: We conclude that addition of clonidine in the dose of 7.5 μg to bupivacaine significantly increases the duration of spinal analgesia with clinically insignificant influence on

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

    Science.gov (United States)

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

    2017-05-01

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

  13. Radiation dose-response of human tumors

    International Nuclear Information System (INIS)

    Okunieff, P.; Morgan, D.; Niemierko, Andrzej; Suit, H.D.

    1995-01-01

    The dose of radiation that locally controls human tumors treated electively or for gross disease is rarely well defined. These doses can be useful in understanding the dose requirements of novel therapies featuring inhomogeneous dosimetry and in an adjuvant setting. The goal of this study was to compute the dose of radiation that locally controls 50% (TCD 50 ) of tumors in human subjects. Logit regression was used with data collected from single institutions or from combinations of local control data accumulated from several institutions treating the same disease. 90 dose response curves were calculated: 62 of macroscopic tumor therapy, 28 of elective therapy with surgery for primary control. The mean and median TCD 50 for gross disease were 50.0 and 51.9 Gy, respectively. The mean and median TCD 50 for microscopic disease control were 39.3 and 37.9 Gy, respectively. At the TCD 50 , an additional dose of 1 Gy controlled an additional 2.5% (median) additional patients with macroscopic disease and 4.2% (median) additional patients with microscopic disease. For both macro- and microscopic disease, an increase of 1% of dose at the TCD 50 increased control rates ∼ 1% (median) or 2-3% (mean). A predominance of dose response curves had shallow slopes accounting for the discrepancy between mean and median values. Doses to control microscopic disease are approximately 12 Gy less than that required to control macroscopic disease and about 79% of the dose required to control macroscopic disease. The percentage increase in cures expected for a 1% increase in dose is similar for macroscopic and microscopic disease, with a median value of ∼ 1%/% and a mean of ∼ 2.7%/%. 94 refs., 4 figs., 6 tabs

  14. Xylitol improves pancreatic islets morphology to ameliorate type 2 diabetes in rats: a dose response study.

    Science.gov (United States)

    Rahman, Md Atiar; Islam, Md Shahdiul

    2014-07-01

    Xylitol has been reported as a potential antidiabetic sweetener in a number of recent studies; however, the most effective dietary dose and organ-specific effects are still unclear. Six-week-old male Sprague-Dawley rats were randomly divided into 5 groups: normal control (NC), diabetic control (DBC), diabetic xylitol 2.5% (DXL2.5), diabetic xylitol 5.0% (DXL5), and diabetic xylitol 10.0% (DXL10). Diabetes was induced only in the animals in DBC and DXL groups and considered diabetic when their nonfasting blood glucose level was >300 mg/dL. The DXL groups were fed with 2.5%, 5.0%, and 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. After 4-wk intervention, body weight, food and fluid intake, blood glucose, serum fructosamine, liver glycogen, serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, creatine kinase, uric acid, creatinine, and most serum lipids were significantly decreased, and serum insulin concentration, glucose tolerance ability, and pancreatic islets morphology were significantly improved in the DXL10 group compared to the DBC group. The data of this study suggest that 10% xylitol has the better antidiabetic effects compared to 2.5% and 5.0% and it can be used as an excellent antidiabetic sweetener and food supplement in antidiabetic foods. Xylitol is widely used as a potential anticariogenic and sweetening agent in a number of oral care and food products when many of its health benefits are still unknown. Due to its similar sweetening power but lower calorific value (2.5 compared with 4 kcal) and lower glycemic index (13 compared with 65) compared to sucrose, recently it has been widely used as a sugar substitute particularly by overweight, obese, and diabetic patients in order to reduce their calorie intake from sucrose. However, the potential antidiabetic effects of xylitol have been discovered recently. The results of this study confirmed the effective dietary dose of xylitol for

  15. Augmentation index (AI) in a dose-response relationship with smoking habits in males: The Tanushimaru study.

    Science.gov (United States)

    Tsuru, Tomoko; Adachi, Hisashi; Enomoto, Mika; Fukami, Ako; Kumagai, Eita; Nakamura, Sachiko; Nohara, Yume; Kono, Shoko; Nakao, Erika; Sakaue, Akiko; Morikawa, Nagisa; Fukumoto, Yoshihiro

    2016-12-01

    We investigated the relationship between augmentation index (AI) and smoking habits in community-dwelling Japanese.This cross-sectional study enrolled 1926 subjects (769 males and 1157 females) aged 40 to 95 years who underwent a health check-up in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town in Kyushu Island in 2009. The subjects' medical history, alcohol intake, smoking habit, and current medications for hypertension, dyslipidemia, and diabetes were ascertained by questionnaire. Radial arterial pressure wave analysis was used to obtain AI. We analyzed the data stratified by gender.Age-adjusted means of AI in males showed a clear dose-response relationship in 4 categories of smoking habits (P = 0.010). There was no significant relationship between AI and smoking habits in females (P = 0.127). The significant dose-response relationship (P = 0.036) in males between AI and 4 categories of smoking habits still remained even after adjustment for age, body mass index, systolic blood pressure, estimated glomerular filtration rate, glucose, hypertensive medication, and alcohol intake.The present study demonstrated that AI values were significantly associated with smoking habits in a dose-dependent manner in Japanese males.

  16. Dose-response association between leisure time physical activity and work ability: Cross-sectional study among 3000 workers.

    Science.gov (United States)

    Calatayud, Joaquin; Jakobsen, Markus D; Sundstrup, Emil; Casaña, Jose; Andersen, Lars L

    2015-12-01

    Regular physical activity is important for longevity and health, but knowledge about the optimal dose of physical activity for maintaining good work ability is unknown. This study investigates the association between intensity and duration of physical activity during leisure time and work ability in relation to physical demands of the job. From the 2010 round of the Danish Work Environment Cohort Study, currently employed wage earners with physically demanding work (n = 2952) replied to questions about work, lifestyle and health. Excellent (100 points), very good (75 points), good (50 points), fair (25 points) and poor (0 points) work ability in relation to the physical demands of the job was experienced by 18%, 40%, 30%, 10% and 2% of the respondents, respectively. General linear models that controlled for gender, age, physical and psychosocial work factors, lifestyle and chronic disease showed that the duration of high-intensity physical activity during leisure was positively associated with work ability, in a dose-response fashion (p physical activity per week had on average 8 points higher work ability than those not performing such activities. The duration of low-intensity leisure-time physical activity was not associated with work ability (p = 0.5668). The duration of high-intensity physical activity during leisure time is associated in a dose-response fashion with work ability, in workers with physically demanding jobs. © 2015 the Nordic Societies of Public Health.

  17. Comparison study of in vivo dose response to laser-driven versus conventional electron beam.

    Science.gov (United States)

    Oppelt, Melanie; Baumann, Michael; Bergmann, Ralf; Beyreuther, Elke; Brüchner, Kerstin; Hartmann, Josefin; Karsch, Leonhard; Krause, Mechthild; Laschinsky, Lydia; Leßmann, Elisabeth; Nicolai, Maria; Reuter, Maria; Richter, Christian; Sävert, Alexander; Schnell, Michael; Schürer, Michael; Woithe, Julia; Kaluza, Malte; Pawelke, Jörg

    2015-05-01

    The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.

  18. Serum Uric Acid Levels and Risk of Metabolic Syndrome: A Dose-Response Meta-Analysis of Prospective Studies.

    Science.gov (United States)

    Yuan, Huiping; Yu, Chenglong; Li, Xinghui; Sun, Liang; Zhu, Xiaoquan; Zhao, Chengxiao; Zhang, Zheng; Yang, Ze

    2015-11-01

    An excess circulating uric acid level, even within the normal range, is always comorbid with metabolic syndrome (MS), several of its components, and nonalcoholic fatty liver disease (NAFLD), which was regarded as hepatic manifestation of MS; however, these associations remain controversial. This study aimed to quantitatively assess the relationship between the serum uric acid (SUA) levels and the MS/NAFLD risk. We searched for related prospective cohort studies including SUA as an exposure and MS/NAFLD as a result in MEDLINE (PubMed) and EMBASE databases up to January 31, 2015 and July 28, 2015, respectively. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were extracted. A random-effects model was used to evaluate dose-response relationships. On the basis of 11 studies (54 970 participants and 8719 MS cases), a combined RR of 1.72 (95% CI, 1.45-2.03; P < .0001) was observed for the highest SUA level category compared with the lowest SUA level category. Furthermore, based on nine studies (51 249 participants and 8265 MS cases), dose-response analysis suggested that each 1 mg/dL SUA increment was roughly linearly associated with the MS risk (RR, 1.30; 95% CI, 1.22-1.38; P < .0001). Beyond that, SUA level increased NAFLD risk (RR, 1.46; 95% CI, 1.31-1.63). Each 1 mg/dL SUA level increment led to 21% increase in the NAFLD risk. This meta-analysis suggests that higher SUA levels led to an increased risk of MS regardless of the study characteristics, and were consistent with a linear dose-response relationship. In addition, SUA was also a causal factor for the NAFLD risk.

  19. A randomized phase II dose-response exercise trial among colon cancer survivors: Purpose, study design, methods, and recruitment results.

    Science.gov (United States)

    Brown, Justin C; Troxel, Andrea B; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S; Rickels, Michael R; Rhim, Andrew D; Rustgi, Anil K; Courneya, Kerry S; Schmitz, Kathryn H

    2016-03-01

    Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the courage trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. The primary objective of the courage trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·week(-1)) and high-dose (300 min·week(-1)) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (Pclinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Fruit and vegetables consumption and incident hypertension: dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Wu, L; Sun, D; He, Y

    2016-10-01

    The role of dietary factors on chronic diseases seems essential in the potentially adverse or preventive effects. However, no evidence of dose-response meta-analysis of prospective cohort studies has verified the association between the intake of fruit and/or vegetables and the risk of developing hypertension. The PubMed and Embase were searched for prospective cohort studies. A generic inverse-variance method with random effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Generalized least squares trend estimation model was used to calculate the study-specific slopes for the dose-response analyses. Seven articles comprised nine cohorts involving 185 676 participants were assessed. The highest intake of fruit or vegetables separately, and total fruit and vegetables were inversely associated with the incident risk of hypertension compared with the lowest level, and the pooled RRs and 95% CIs were 0.87 (0.79, 0.95), 0.88 (0.79, 0.99) and 0.90 (0.84, 0.98), respectively. We also found an inverse dose-response relation between the risk of developing hypertension and fruit intake, and total fruit and vegetables consumption. The incident risk of hypertension was decreased by 1.9% for each serving per day of fruit consumption, and decreased by 1.2% for each serving per day of total fruit and vegetables consumption. Our results support the recommendation to increase the consumption of fruit and vegetables with respect to preventing the risk of developing hypertension. However, further large prospective studies and long-term high-quality randomized controlled trials are still needed to confirm the observed association.

  1. Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Grosso, Giuseppe; Micek, Agnieszka; Castellano, Sabrina; Pajak, Andzrej; Galvano, Fabio

    2016-01-01

    The aim of the study was to systematically review and analyze results from observational studies on coffee, caffeine, and tea consumption and association or risk of depression. Embase and PubMed databases were searched from inception to June 2015 for observational studies reporting the odds ratios or relative risks (RRs) and 95% confidence intervals (CI) of depression by coffee/tea/caffeine consumption. Random effects models, subgroup analyses, and dose-response analyses were performed. Twelve studies with 23 datasets were included in the meta-analysis, accounting for a total of 346 913 individuals and 8146 cases of depression. Compared to individuals with lower coffee consumption, those with higher intakes had pooled RR of depression of 0.76 (95% CI: 0.64, 0.91). Dose-response effect suggests a nonlinear J-shaped relation between coffee consumption and risk of depression with a peak of protective effect for 400 mL/day. A borderline nonsignificant association between tea consumption and risk of depression was found (RR 0.70, 95% CI: 0.48, 1.01), while significant results were found only for analysis of prospective studies regarding caffeine consumption (RR = 0.84, 95% CI: 0.75, 0.93). This study suggests a protective effect of coffee and, partially, of tea and caffeine on risk of depression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. 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

    2016-01-01

    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.

  3. In vitro study of dose-response relationship of fluoride with dental enamel

    Directory of Open Access Journals (Sweden)

    Arthur, Rodrigo Alex et al.

    2007-01-01

    Full Text Available Modelos in vitro para avaliação da reatividade do fluoreto (F devem apresentar resposta dose-efeito. Dessa forma, o objetivo desse estudo foi avaliar a relação dose-resposta do fluoreto presente em solução aquosa com o esmalte dental bovino. Cento e vinte blocos de esmalte bovino (5 × 5 × 2 mm, 60 hígidos e 60 com lesão artificial de cárie, foram submetidos durante 10 minutos à água destilada e deionizada (controle negativo e soluções aquosas contendo 50, 100, 200 ou 400 µg F/mL. Cada grupo experimental recebeu 12 blocos hígidos e 12 blocos com lesão artificial de cárie. Duas camadas consecutivas de esmalte dental foram removidas de todos os blocos dentais por meio de ataque ácido e o fluoreto extraído foi determinado com eletrodo específico. Os resultados de fluoreto incorporado foram expressos em µg por g de esmalte removido, considerando a quantidade total das duas camadas. A incorporação de fluoreto pelo esmalte hígido mostrou uma relação dose-resposta linear (p = 0,0001, enquanto que os blocos com lesão de cárie mostraram relação polinomial quadrática (p < 0,0001. Os resultados sugerem que o modelo in vitro de reatividade empregado no presente estudo é apropriado para avaliar a relação doseresposta entre o fluoreto em solução aquosa e aquele incorporado pelo esmalte dental bovino hígido ou com lesão artificial de cárie.

  4. Statins intake and risk of liver cancer: A dose-response meta analysis of prospective cohort studies.

    Science.gov (United States)

    Yi, Changhong; Song, Zhenggui; Wan, Maolin; Chen, Ya; Cheng, Xiang

    2017-07-01

    Previous studies have indicated that statins intake was associated with liver cancer risk, but presented controversial results.Studies in PubMed and EMBASE were searched update to February 2017 to identify and quantify the potential dose-response association between statins intake and liver cancer.Six eligible studies involving a total of 11,8961 participants with 9530 incident cases were included in this meta-analysis. Statistically significant association was observed between increasing statins intake and liver cancer risk reduction (OR = 0.46, 95%CI: 0.24-0.68, P risk of liver cancer for an increase of 50 cumulative defined daily dose per year was 0.86 (95%CI: 0.81-0.90, P risk was found (P for nonlinearity analysis indicated that statins intake was associated with a significantly risk of liver cancer risk reduction in Asia (OR = 0.44, 95%CI: 0.11-0.77, P risk reduction.

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

    Science.gov (United States)

    Weng, Ke-Gui; Yuan, Ya-Ling

    2017-08-01

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

  6. Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships.

    Science.gov (United States)

    Paek, Domyung; Koh, Younsuck; Park, Dong-Uk; Cheong, Hae-Kwan; Do, Kyung-Hyun; Lim, Chae-Man; Hong, Soo-Jong; Kim, Yong-Hwa; Leem, Jong-Han; Chung, Kyu Hyuck; Choi, Ye-Yong; Lee, Jong-Hyeon; Lim, Sin-Ye; Chung, Eun-Hee; Cho, Young Ah; Chae, Eun Jin; Joh, Joon-Sung; Yoon, Yup; Lee, Kyu-Hong; Choi, Bo Youl; Gwack, Jin

    2015-12-01

    Humidifier disinfectant lung injury is an acute lung disease attributed to recurrent inhalation of certain disinfectant aerosols emitted from room humidifiers. An outbreak of this toxic lung injury occurred in South Korea from 1995 until all humidifier disinfectant products were recalled from the consumer market by the government in 2011. A nationwide study was conducted to ascertain and classify all potential cases of humidifier disinfectant lung injury in Korea and to assess dose-response relationships. By several mechanisms, clinicians and the general public were invited to report all suspected cases of humidifier disinfectant lung injury to public health officials in South Korea. A committee was convened to define diagnostic criteria based on pathologic, radiologic, and clinical findings for index cases, combined with assessment of environmental exposure to humidifier disinfectants. Clinical review and environmental assessments were performed and later combined to determine overall likelihood of disease for each study participant, classified as definite, probable, possible, or unlikely. Survival time from exposure to onset of symptoms was analyzed to assess dose-response relationships. Three broad categories of risk factors were examined: (1) biological susceptibility, (2) temporal cycle of exposure and recovery, and (3) spatial conditions and density of disinfectant. Of 374 possible cases identified and reviewed, 329 were unanimously classified by the diagnostic committee, as follows: 117 definite, 34 probable, 38 possible and 140 unlikely cases. A total of 62 individuals with definite or probable disease died. Risk factors examined for polyhexamethyleneguanidine phosphate exposure that were found to be significant in shortening survival included age 4 years or younger at onset, use of disinfectant for 7 days per week, airborne density of 800 μg/m(3) or more of disinfectant, and daily exposure 11 or more hours in duration. Dose-response analysis indicated

  7. Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study

    Directory of Open Access Journals (Sweden)

    Mireille Matrat

    2015-01-01

    Full Text Available Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME, taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent.

  8. Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study

    Science.gov (United States)

    Matrat, Mireille; Guida, Florence; Cénée, Sylvie; Févotte, Joelle; Carton, Matthieu; Cyr, Diane; Menvielle, Gwenn; Paget-Bailly, Sophie; Radoï, Loredana; Schmaus, Annie; Bara, Simona; Velten, Michel; Luce, Danièle; Stücker, Isabelle; The Icare Study Group

    2015-01-01

    Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent. PMID:26425123

  9. Human Health Risk Assessment: A case study application of principles in dose response assessment

    Science.gov (United States)

    This case study application workshop will build on fundamental concepts and techniques in risk assessment presented and archived at previous TRAC meeting workshops. Practical examples from publicly available, peer reviewed risk assessments will be used as teaching aids. Course ...

  10. Dose-Response Relationship Between Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) and Stroke: A Chinese Case-Control Study

    Science.gov (United States)

    Dai, Huixu; Shi, Jingpu; He, Qiao; Sun, Hao

    2017-01-01

    Background Because TAFI (thrombin-activatable fibrinolysis inhibitor) antigen varies widely among different populations, we performed this case-control study to explore the relationship between TAFI levels and stroke in a Chinese population. Material/Methods Our population-based case-control study included 217 stroke patients and 218 healthy controls. The plasma TAFI level was measured by immune turbidimetry. Univariate and multivariate logistic regression analyses were used to analyze the association between different TAFI levels and stroke and its subtypes. Restricted cubic spline (RCS) combined with logistic regression analysis were used to explore the dose-response relationship between TAFI levels and stroke. Results The plasma TAFI levels of cases were much higher than in the control group (p=0.038) and this difference persisted even after adjustment (OR=2.2). In the elderly (aged over 60) and female subgroups, TAFI levels in stroke patients were higher than those in controls, and the results were also noted in ischemic stroke. The dose-response curve showed that, as a whole, with the increase of TAFI levels, the relative risk of stroke first increased and then decreased (p=0.0127). Similarly, in general, with the increase of TAFI levels, the curve showed that the relative risk of ischemic stroke first increased and then decreased (p=0.0110). Conclusions There was a definite correlation between TAFI levels and stroke in this Chinese population, and with the increase of TAFI levels, the relative risk of stroke or ischemic stroke first increased and then decreased. PMID:28890533

  11. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Larsson, Susanna C; Orsini, Nicola

    2011-11-01

    Coffee consumption has been inconsistently associated with risk of stroke. The authors conducted a meta-analysis of prospective studies to quantitatively assess the association between coffee consumption and stroke risk. Pertinent studies were identified by searching PubMed and Embase from January 1966 through May 2011 and by reviewing the reference lists of retrieved articles. Prospective studies in which investigators reported relative risks of stroke for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Eleven prospective studies, with 10,003 cases of stroke and 479,689 participants, met the inclusion criteria. There was some evidence of a nonlinear association between coffee consumption and risk of stroke (P for nonlinearity = 0.005). Compared with no coffee consumption, the relative risks of stroke were 0.86 (95% confidence interval (95% CI): 0.78, 0.94) for 2 cups of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3-4 cups/day, 0.87 (95% CI: 0.77, 0.97) for 6 cups/day, and 0.93 (95% CI: 0.79, 1.08) for 8 cups/day. There was marginal between-study heterogeneity among study-specific trends (I₂ = 12% and I₂ = 20% for the first and second spline transformations, respectively). Findings from this meta-analysis indicate that moderate coffee consumption may be weakly inversely associated with risk of stroke.

  12. EFFECTS OF PREANESTHETIC SINGLE DOSE INTRAVENOUS DEXMEDETOMIDINE VERSUS FENTANYL ON HEMODYNAMIC RESPONSE TO ENDOTRACHEAL INTUBATION-A CLINICAL COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Chandita

    2015-12-01

    Full Text Available INTRODUCTION Many pharmacological agents have been evaluated in regards to their efficacy of blunting the adverse cardiovascular response to laryngoscopy and tracheal intubation. The aim of this study was to evaluate the efficacy of dexmedetomidine compared to fentanyl in blunting the haemodynamic response to laryngoscopy and intubation. METHOD Sixty patients were randomly allocated into two groups (30 patients in each group. The group D received intravenously 1 µgm/kg dexmedetomidine infusion and group F received 2µgm/kg fentanyl infusion. The study drugs were prepared in an identical looking container and were infused fifteen minutes prior to induction of anaesthesia. The study drugs were infused over a period of ten minutes and all the patients underwent a similar anaesthetics technique. Heart rate (HR and blood pressure (systolic, diastolic and mean blood pressure were noted at baseline, at the end of infusion of the study drugs, after induction of anaesthesia, immediately after laryngoscopy and intubation and at 1, 3, 5, 7 and 10 minutes after laryngoscopy and intubation. RESULTS HR significantly decreased in the group D when compared to group F immediately after study drug infusion and there was statistically significant reduction in heart rate for up to 5 min after intubation in both the groups. Although HR increased after intubation in both the groups, the magnitude was lower in the group D. In both the groups, laryngoscopy and intubation led to an increase in systolic, diastolic and mean arterial pressure; the magnitude was lower in the group D. CONCLUSION Dexmeditomidine (1µ/kg attenuates these untoward responses of laryngoscopy and intubation more effectively than fentanyl (2 µ/kg when administered as bolus dose in the pre-induction period of general anaesthesia.

  13. Absorption, Metabolism and Excretion of Cranberry (Polyphenols in Humans: A Dose Response Study and Assessment of Inter-Individual Variability

    Directory of Open Access Journals (Sweden)

    Rodrigo P. Feliciano

    2017-03-01

    Full Text Available The beneficial health effects of cranberries have been attributed to their (polyphenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (polyphenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (polyphenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (polyphenol metabolites, exhibited a linear dose response (r2 = 0.74, p < 0.05, driven by caffeic acid 4-O-ß-d-glucuronide, quercetin-3-O-ß-d-glucuronide, ferulic acid 4-O-ß-d-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O-ß-d-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R-5-(3′-hydroxyphenyl-γ-valerolactone-4′-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r2 ≥ 0.89, p < 0.05. Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (polyphenol metabolites are linearly related to the amount of (polyphenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.

  14. High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (Clopidogrel and Response Variability Investigation Study 2).

    Science.gov (United States)

    Collet, Jean-Philippe; Hulot, Jean-Sébastien; Anzaha, Ghalia; Pena, Ana; Chastre, Thomas; Caron, Claire; Silvain, Johanne; Cayla, Guillaume; Bellemain-Appaix, Anne; Vignalou, Jean-Baptiste; Galier, Sophie; Barthélémy, Olivier; Beygui, Farzin; Gallois, Vanessa; Montalescot, Gilles

    2011-04-01

    This study sought to determine whether the pharmacokinetic (PK) and pharmacodynamic (PD) responses to high or standard clopidogrel loading doses (LDs) differ according to CYP2C19*2 allele. CYP2C19 loss-of-function alleles are associated with reduced responsiveness to standard clopidogrel doses. Young post-myocardial infarction patients heterozygous (wild type [wt]/*2, n = 43) or homozygous (*2/*2, n = 8) for the CYP2C19*2 genetic variant were matched with patients not carrying the variant (wt/wt, n = 58). All patients were randomized to a 300- or 900-mg clopidogrel LD. The relative reduction in residual platelet aggregation (RR-RPA, %) and the area under the plasma concentration time curve of active metabolite from baseline to 6 h after loading (AUC(0-6)) were compared according to both LD and CYP2C19*2 carriage. The 300-mg LD led to a gene-dose effect for RR-RPA (-65.7% ± 35.9% in wt/wt vs. -48.0% ± 38.4% in wt/*2 vs. -14.6% ± 32.4% in *2/*2; overall p value = 0.003, p = 0.03 for wt/wt versus wt/*2, p = 0.04 for wt/*2 versus *2/*2) with minor effect in *2/*2 carriers. After the 900-mg LD, the effect of the CYP2C19*2 variant on platelet inhibition was fully compensated in wt/*2 carriers but not in *2/*2 carriers (-83.6% ± 25.8% in wt/wt vs.-77.2% ± 26.9% in wt/*2 vs. -29.5% ± 26.8% in *2/*2; overall p value = 0.0003, p = 0.20 for wt/wt versus wt/*2, p CLOVIS-2]; NCT00822666). Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Dietary fiber intake and risk of type 2 diabetes: a dose-response analysis of prospective studies.

    Science.gov (United States)

    Yao, Baodong; Fang, Hong; Xu, Wanghong; Yan, Yujie; Xu, Huilin; Liu, Yinan; Mo, Miao; Zhang, Hua; Zhao, Yanping

    2014-02-01

    Observational studies suggest an association between dietary fiber intake and risk of type 2 diabetes, but the results are inconclusive. We conducted a meta-analysis of prospective studies evaluating the associations of dietary fiber intake and risk of type 2 diabetes. Relevant studies were identified by searching EMBASE (from 1974 to April 2013) and PubMed (from 1966 to April 2013). The fixed or random-effect model was selected based on the homogeneity test among studies. In addition, a 2-stage random-effects dose-response meta-analysis was performed. We identified 17 prospective cohort studies of dietary fiber intake and risk of type 2 diabetes involving 19,033 cases and 488,293 participants. The combined RR (95 % CI) of type 2 diabetes for intake of total dietary fiber, cereal fiber, fruit fiber and insoluble fiber was 0.81 (0.73-0.90), 0.77 (0.69-0.85), 0.94 (0.88-0.99) and 0.75 (0.63-0.89), respectively. A nonlinear relationship was found of total dietary fiber intake with risk of type 2 diabetes (P for nonlinearity fiber intake. Findings from this meta-analysis indicate that the intakes of dietary fiber may be inversely associated with risk of type 2 diabetes.

  16. Measures of Abdominal Adiposity and Risk of Stroke: A Dose-Response Meta-analysis of Prospective Studies.

    Science.gov (United States)

    Zhong, Chong Ke; Zhong, Xiao Yan; Xu, Tan; Zhang, Yong Hong

    2016-01-01

    Waist circumference, waist-to-hip ratio and waist-to-height ratio, which are the indicators or measures of abdominal adiposity, have long been hypothesized to increase the risk of stroke; yet evidence accumulated till date is not conclusive. Here, we conducted a dose-response meta-analysis to summarize evidences of the association between these measures of abdominal adiposity and the risk of stroke. PubMed and Web of Science databases were searched from inception to May 2015. Two investigators independently conducted the study selection and data extraction. Dose-response relationships were assessed by the generalized least squares trend estimation, while the summary effect estimates were evaluated by the use of fixed- or random-effect models. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Publication bias of the literature was evaluated using Begg's and Egger's test. Altogether 15 prospective cohort studies were identified in this study. The summary of relative risks (95% confidence intervals) of stroke for the highest versus the lowest categories was 1.28 (1.18-1.40) for waist circumference, 1.32 (1.21-1.44) for waist-to-hip ratio, and 1.49 (1.24-1.78) for waist-to-height ratio. For a 10-cm increase in waist circumference, the relative risk of stroke increased by 10%; for a 0.1-unit increase in waist-to-hip ratio, the relative risk increased by 16%; and for a 0.05-unit increase in waist-to-height ratio, the relative risk increased by 13%. There was evidence of a nonlinear association between waist-to-hip ratio and stroke risk, Pnonlinearity=0.028. Findings from our meta-analysis indicated that waist circumference, waist-to-hip ratio, and waist-to-height ratio were positively associated with the risk of stroke, particularly ischemic stroke. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  17. Acute Effects of Classroom Exercise Breaks on Executive Function and Math Performance: A Dose-Response Study.

    Science.gov (United States)

    Howie, Erin K; Schatz, Jeffrey; Pate, Russell R

    2015-01-01

    The purpose of this study was to determine the acute dose-response relationship of classroom exercise breaks with executive function and math performance in 9- to 12-year-old children by comparing 5-min, 10-min, or 20-min classroom exercise breaks to 10 min of sedentary classroom activity. This study used a within-subjects experimental design conducted in the spring of 2012. Ninety-six 4th- and 5th-grade students in 5 classrooms in South Carolina were randomized to receive each of 4 treatments: 5-min, 10-min, or 20-min exercise breaks or 10 min of a sedentary lesson led by research staff. Students completed the Trail-Making Test, an Operational Digit Recall test, and a math fluency test immediately before and after each condition. Planned linear contrasts were used to compare posttest scores between conditions using a repeated-measures mixed model, adjusted for gender, classroom, and the time-varying pretest scores. Potential effect modifiers were added as interaction terms. Math scores were higher after the 10-min and 20-min exercise breaks compared with the sedentary condition (d = 0.24, p = .04, and d = 0.27, p = .02, respectively), and an interaction was observed with gender, IQ, aerobic fitness, and lower engagement in some of the conditions. There were no improvements in executive function tasks. A 10-min and 20-min classroom exercise break moderately improved math performance in students compared with a seated classroom lesson.

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

    Science.gov (United States)

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

    2014-12-01

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

  19. A review of dosimetry used in epidemiological studies considered to evaluate the linear no-threshold (LNT) dose-response model for radiation protection.

    Science.gov (United States)

    Till, John E; Beck, Harold L; Grogan, Helen A; Caffrey, Emily A

    2017-10-01

    Accurate dosimetry is key to deriving the dose response from radiation exposure in an epidemiological study. It becomes increasingly important to estimate dose as accurately as possible when evaluating low dose and low dose rate as the calculation of excess relative risk per Gray (ERR/Gy) is very sensitive to the number of excess cancers observed, and this can lead to significant errors if the dosimetry is of poor quality. By including an analysis of the dosimetry, we gain a far better appreciation of the robustness of the work from the standpoint of its value in supporting the shape of the dose response curve at low doses and low dose rates. This article summarizes a review of dosimetry supporting epidemiological studies currently being considered for a re-evaluation of the linear no-threshold assumption as a basis for radiation protection. The dosimetry for each study was evaluated based on important attributes from a dosimetry perspective. Our dosimetry review consisted of dosimetry supporting epidemiological studies published in the literature during the past 15 years. Based on our review, it is clear there is wide variation in the quality of the dosimetry underlying each study. Every study has strengths and weaknesses. The article describes the results of our review, explaining which studies clearly stand out for their strengths as well as common weaknesses among all investigations. To summarize a review of dosimetry used in epidemiological studies being considered by the National Council on Radiation Protection and Measurements (NCRP) in an evaluation of the linear no-threshold dose-response model that underpins the current framework of radiation protection. The authors evaluated each study using criteria considered important from a dosimetry perspective. The dosimetry analysis was divided into the following categories: (1) general study characteristics, (2) dose assignment, (3) uncertainty, (4) dose confounders (5) dose validation, and (6) strengths and

  20. Dose-Response Analysis Using R.

    Directory of Open Access Journals (Sweden)

    Christian Ritz

    Full Text Available 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 number of extractors for summarizing fitted models and carrying out inference on derived parameters. The aim of the present paper is to provide an overview of state-of-the-art dose-response analysis, both in terms of general concepts that have evolved and matured over the years and by means of concrete examples.

  1. Alleviating stress response to tracheal extubation in neurosurgical patients: A comparative study of two infusion doses of dexmedetomidine

    Directory of Open Access Journals (Sweden)

    Ankur Luthra

    2017-01-01

    Full Text Available Background: Tracheal extubation is almost always associated with increase in sympathoadrenal activity may result in hypertension, tachycardia, and arrhythmias. Attempts have been made to oppose the pressor response by the use of various drugs. Dexmedetomidine decreases norepinephrine which reduces the blood pressure and the heart rate (HR. We hypothesize that the infusion of dexmedetomidine may produce more stable hemodynamics during extubation as compared to boluses. Materials and Methods: Ninety adult patients aged 18–65 years, the American Society of Anesthesiologists Grade I–II undergoing intracranial surgeries for various neurologic problem at All India Institute of Medical Sciences were enrolled in this randomized controlled trial. Primary Objectives: (1 To observe the hemodynamic changes (HR and mean arterial pressure [MAP] and airway responses during tracheal extubation following two infusion doses of dexmedetomidine. Secondary Objectives: (1 Time to emergence and time to tracheal extubation, (2 Early postoperative complications such as laryngospasm and bronchospasm, and (3 adverse effects of the study drug. Patients were assigned into three groups – (1 Group D0.2 – 0.2 μg/kg/h diluted to 50 ml, (2 Group D0.4 – 0.4 μg/kg/h diluted to 50 ml and Group P (Placebo – 0.9% NS 50 ml. The hemodynamics including the HR and MAP were recorded just before the loading dose of the study drug and then were recorded every 5 min till the infusion was stopped at tracheal extubation and every 1 min till 10 min postextubation. In addition, the airway, respiratory and cardiovascular complications along with postoperative nausea and vomiting, shivering, cough grading, Aldrete score, Ramsay sedation scale, and intraoperative awareness were recorded. Statistical Analysis: Continuous variables such as HR and MAP were analyzed using analysis of variance and categorical variables were analyzed using the Chi-square test. Results: Patient demographics

  2. Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

    Energy Technology Data Exchange (ETDEWEB)

    Pisansky, Thomas M., E-mail: pisansky.thomas@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Agrawal, Shree [Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Hamstra, Daniel A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Koontz, Bridget F. [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Liauw, Stanley L. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Efstathiou, Jason A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abramowitz, Matthew C.; Pollack, Alan [Department of Radiation Oncology, University of Miami, Miami, Florida (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Moghanaki, Drew [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia (United States); Den, Robert B. [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Stephans, Kevin L. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lee, W. Robert [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Kattan, Michael W. [Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio (United States); and others

    2016-12-01

    Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

  3. Dose-Response Calculator for ArcGIS

    Science.gov (United States)

    Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

    2011-01-01

    The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

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

    International Nuclear Information System (INIS)

    Maier, D.M.; Landauer, M.R.

    1989-01-01

    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

  5. Restoration of cardiac tissue thyroid hormone status in experimental hypothyroidism: a dose-response study in female rats.

    Science.gov (United States)

    Weltman, Nathan Y; Ojamaa, Kaie; Savinova, Olga V; Chen, Yue-Feng; Schlenker, Evelyn H; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Pol, Christine J; Gerdes, A Martin

    2013-07-01

    Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T(3) (instead of T(4)) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T(3) dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T(3) and T(4) levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T(3) led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T(3) levels was not associated with restoration of cardiac tissue T(3) levels or cardiac function. In fact, a 3-fold higher T(3) dosage was necessary to normalize cardiac tissue T(3) levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states.

  6. Biostatistical approaches for modeling U-shaped dose-response curves and study design considerations in assessing the biological effects of low doses

    International Nuclear Information System (INIS)

    Downs, T.

    1992-01-01

    The demonstration of hormetic effects is rendered difficult for a number of reasons: The spontaneous rate must be large enough for a difference to be detectable. In contrast with detrimental effects, there is a limited range of doses over which beneficial effects are likely to be found. Publication bias hampers publication of low-dose beneficial effects and discourages research in the area. Some scientists actually believe that hormetic effects are contary to reason. All these factors contribute to lessen the chances of detecting hormetic effects through synthesis of the scientific literature. The extra statistical power obtained from mathematical modeling is not available for hormetic studies when appropriate models are not available. Even a simple statistical device such as a test for linear trend does not work well for U-shaped data. The first part of this two-part chapter deals with the probabilities of determining qualitatively what kinds of health effects may result from exposures to substances, and the second part with characterizing quantitative relationships between such health effects and exposures. The health effects may be beneficial in some situations, and detrimental in others

  7. Dietary Protein Sources and Incidence of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies

    Directory of Open Access Journals (Sweden)

    Jing Wu

    2016-11-01

    Full Text Available Protein is important to the human body, and different sources of protein may have different effects on the risk of breast cancer. Thus, we conducted a meta-analysis to investigate the association between different dietary protein sources and breast cancer risk. PubMed and several databases were searched until December 2015. Relevant articles were retrieved according to specific searching criteria. Forty-six prospective studies were included. The summary relative risk (RR for highest versus lowest intake was 1.07 (95% confidence interval (CI 1.01–1.14, I2 = 34.6% for processed meat, 0.92 (95% CI 0.84–1.00, I2 = 0% for soy food, 0.93 (95% CI 0.85–1.00, I2 = 40.1% for skim milk, and 0.90 (95% CI 0.82–1.00, I2 = 0% for yogurt. Similar conclusions were obtained in dose-response association for each serving increase: total red meat (RR: 1.07; 95% CI 1.01–1.14, I2 = 7.1%, fresh red meat (RR: 1.13; 95% CI 1.01–1.26, I2 = 56.4%, processed meat (RR: 1.09; 95% CI 1.02–1.17, I2 = 11.8%, soy food (RR: 0.91; 95% CI 0.84–1.00, I2 = 0%, and skim milk (RR: 0.96; 95% CI 0.92–1.00, I2 = 11.9%. There was a null association between poultry, fish, egg, nuts, total milk, and whole milk intake and breast cancer risk. Higher total red meat, fresh red meat, and processed meat intake may be risk factors for breast cancer, whereas higher soy food and skim milk intake may reduce the risk of breast cancer.

  8. 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 analy...

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

    International Nuclear Information System (INIS)

    Lara, Virginia E. Noval; Pineda Bolivar, William R.; Riano, Victor M. Pabon; Ureana, Cecilia Crane

    2013-01-01

    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-to-man studies

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Dose-to-Man Studies focused on developing computer data handling and computer modules which permit easy, rapid assessment of the dose to southeastern United States populations from routine or accidental releases of radionuclides to atmospheric and stream systems

  11. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  12. 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

  13. Association between serum selenium level and type 2 diabetes mellitus: a non-linear dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Wang, Xin-Liang; Yang, Tu-Bao; Wei, Jie; Lei, Guang-Hua; Zeng, Chao

    2016-05-04

    The association between serum selenium levels and type 2 diabetes mellitus (T2DM) is controversial. We performed a systematic review and non-linear dose-response meta-analysis of observational studies to investigate the association in the present study. A comprehensive literature search was conducted using MEDLINE and EMBASE databases. A pooled odds ratio (OR) and related 95 % confidence interval (95 % CI) for T2DM between the highest and lowest serum selenium categories, and a non-linear dose-response relationship between selenium and T2DM were estimated. A total of five studies (of 13,460 participants) were identified as meeting the inclusion criteria. The pooled OR indicated that there was a significantly higher prevalence of T2DM in the highest category of blood selenium compared with the lowest (OR = 1.63, 95 % CI: 1.04-2.56, P = 0.033). Moreover, a significant non-linear dose-response relationship was observed between serum selenium levels and T2DM (P 132.5 μg/l). The positive association between serum selenium levels and T2DM existed in populations with relatively low levels and high levels of serum selenium, indicating a likely U-shaped non-linear dose-response relationship between serum selenium and T2DM.

  14. Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies

    Directory of Open Access Journals (Sweden)

    Xin Fang

    2016-11-01

    Full Text Available The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs, odds ratios (ORs or hazard ratios (HRs, for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%–13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

  15. Comparative study of nuclear magnetic resonance and UV-visible spectroscopy dose-response of polymer gel based on N-(Isobutoxymethyl) acrylamide

    Science.gov (United States)

    Lotfy, S.; Basfar, A. A.; Moftah, B.; Al-Moussa, A. A.

    2017-12-01

    A comparative study of nuclear magnetic resonance and UV-visible spectroscopy of dose-response for polymer gel dosimeters was performed. Dosimeters were prepared using N-(Isobutoxymethyl) acrylamide (NIBMA) as a new monomer via radiation induced polymerization for use in radiotherapy planning. The prepared dosimeters were irradiated with doses up to 30 Gy at a constant dose rate of 600 MU/min. Using a medical linear accelerator at irradiation energies of 6, 10 and 18 MV photon beam. The nuclear magnetic resonance (NMR), via spin-spin relaxation rate (R2) for water proton surrounding the polymer formulation and UV-Visible spectroscopy, via the optical absorbance measurements of irradiated dosimeters at selected wavelengths of 500 nm, was used to investigate the dose response of NIBMAGAT gel dosimeters. Scavenge of oxygen was done using tetrakis (hydroxymethyl) phosphonium chloride (THPC). The THPC optimum concentration in the dosimeters formulations were 5 and 10 mM for the NMR and optical absorbance measurements respectively. The quantitative investigation of the dosimeters components reveals the selective formulations based on 4% w/w gelatin, 1% w/w NIBMA, 3% w/w BisAAm, 5 or 10 mM THPC and 17% w/w glycerol which significantly increase the dosimeters dose response. The prepared dosimeters were found to be dose rate and photon beam irradiation energy independent. The stability study shows no change in the relaxation rate or in the optical absorbance of the gel dosimeters up to 8 days post-irradiation. The prepared polymer gel dosimeters at the energies of 6, 10 and 18 MV photon beam irradiation in the range of 1-30 Gy have the linearity of the dose response function in the case of R2 is better than in the case of absorbance measurements; correlation coefficient (r2) equals 0.995 and 0.991, respectively. Dose sensitivity, R2 of NIBMAGAT dosimeters (0.0775 s-1 Gy-1). The absorption band intensity increases linearly with a dose sensitivity of 0.016 cm-1 Gy-1. The

  16. The Prevalence and Clinical Features of Non-responsive Gastroesophageal Reflux Disease to Practical Proton Pump Inhibitor Dose in Korea: A Multicenter Study.

    Science.gov (United States)

    Park, Hong Jun; Park, Soo Heon; Shim, Ki Nam; Kim, Yong Sung; Kim, Hyun Jin; Han, Jae Pil; Kim, Yong Sik; Bang, Byoung Wook; Kim, Gwang Ha; Baik, Gwang Ho; Kim, Hyung Hun; Park, Seon Young; Kim, Sung Soo

    2016-07-25

    In Korea, there are no available multicenter data concerning the prevalence of or diagnostic approaches for non-responsive gastroesophageal reflux disease (GERD) which does not respond to practical dose of proton pump inhibitor (PPI) in Korea. The purpose of this study is to evaluate the prevalence and the symptom pattern of non-responsive GERD. A total of 12 hospitals who were members of a Korean GERD research group joined this study. We used the composite score (CS) as a reflux symptom scale which is a standardized questionnaire based on the frequency and severity of typical symptoms of GERD. We defined "non-responsive GERD" as follows: a subject with the erosive reflux disease (ERD) whose CS was not decreased by at least 50% after standard-dose PPIs for 8 weeks or a subject with non-erosive reflux disease (NERD) whose CS was not decreased by at least 50% after half-dose PPIs for 4 weeks. A total of 234 subjects were analyzed. Among them, 87 and 147 were confirmed to have ERD and NERD, respectively. The prevalence of non-responsive GERD was 26.9% (63/234). The rates of non-responsive GERD were not different between the ERD and NERD groups (25.3% vs. 27.9%, respectively, p=0.664). There were no differences between the non-responsive GERD and responsive GERD groups for sex (p=0.659), age (p=0.134), or BMI (p=0.209). However, the initial CS for epigastric pain and fullness were higher in the non-responsive GERD group (p=0.044, p=0.014, respectively). In conclusion, this multicenter Korean study showed that the rate of non-responsive GERD was substantially high up to 26%. In addition, the patients with the non-responsive GERD frequently showed dyspeptic symptoms such as epigastric pain and fullness.

  17. Assembled cross-species perchlorate dose-response data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set contains dose-response data for perchlorate exposure in multiple species. These data were assembled from peer-reviewed studies. Species included in...

  18. Multicenter phase II randomized study evaluating dose-response of antiperistaltic effect of L-menthol sprayed onto the gastric mucosa for upper gastrointestinal endoscopy.

    Science.gov (United States)

    Hiki, Naoki; Kaminishi, Michio; Yasuda, Kenjiro; Uedo, Noriya; Kobari, Masumi; Sakai, Terufumi; Hiratsuka, Takashi; Ohno, Kyota; Honjo, Hajime; Nomura, Sachiyo; Yahagi, Naohisa; Tajiri, Hisao; Suzuki, Hiroaki

    2012-03-01

    Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation. In this phase II, multicenter, double-blind, dose-response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy. The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P peristalsis after administration was significantly higher in the 0.8% group (P = 0.015) and 1.6% group (P = 0.009). Adverse events in the L-menthol dose groups occurred with similar frequencies in the placebo group. L-menthol suppresses peristalsis in a dose-dependent manner, and the dose-response reaches a plateau at 0.8% L-menthol. Further Phase III studies are needed to establish the superiority of 0.8% L-menthol over placebo. © 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.

  19. The effect of doxorubicin loading on response and toxicity with drug-eluting embolization in resectable hepatoma: a dose escalation study.

    Science.gov (United States)

    Klass, Darren; Owen, David; Buczkowski, Andrezj; Chung, Stephen W; Scudamore, Charles H; Weiss, Alan A; Yoshida, Eric M; Ford, Jo-Ann E; Ho, Stephen; Liu, David M

    2014-07-01

    The dose-response relationship between doxorubicin and superabsorbent drug-eluting microspheres has not been established. In this study, we investigated the relationships between dose and delivery parameters as they pertain to toxicity and response in surgically resectable hepatocellular carcinoma (HCC). Twenty-five patients with resectable HCC were randomly assigned and divided into four groups, each receiving either bland, 25 mg, 50 mg or 75 mg of doxorubicin loaded Super Absorbent Polymer microspheres, with 24 patients undergoing surgical resection. Response Evaluation and Criteria in Solid Tumors (RECIST) 1.0 and European Association for the Study of the Liver (EASL)-based volumetric response was performed at one month and surgical resection of the reference tumor was performed at two months. Adverse events were collected at regular intervals. Fifty-six percent of patients demonstrated complete response according to EASL criteria as opposed to 0% according to RECIST (v1.0) criteria. Residual tumor was identified in all groups (0 mg: 35%±28.5%; 25 mg: 42%±30.4%; 50 mg: 3.6%±3.3%; and 75 mg: 49.29%±32.6%. A total of 112 adverse events of grades 1-3 occurred (average 5.1 per patient), with no grade 4 or 5. No difference was noted between bland embolic and drug-loaded groups. Subset analysis did demonstrate a significantly increased degree of necrosis in the 50 mg-loaded group (p=0.018). Strong correlation existed between arterial phase Computer Tomography EASL-based response and histopathology (r=0.81; p<0.0001). All groups had residual tumor. Histology correlates strongly with one-month post-procedural imaging and response optimized at 50 mg of loading per vial. Adverse events were a reflection of embolization, with no relationship between loading dose or administered dose of doxorubicin. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) Dose-Response Studies: Preliminary Literature Search Results and Request for Additional Studies

    Science.gov (United States)

    EPA invited the public to comment on the preliminary list of in vivo mammalian dose-response citations for 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). This list was compiled as a first step in the development of EPA’s response to the National Academy of Sciences comments (NAS, 2...

  1. 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...

  2. Long-term fate of crankcase oil in rainbow trout: A time- and dose-response study

    International Nuclear Information System (INIS)

    Hellou, J.; Warren, W.; Andrews, C.; Mercer, G.; Payne, J.F.; Howse, D.

    1997-01-01

    Rainbow trout (Oncorhynchus mykiss) were exposed to waste crankcase oil, a recognized source of polycyclic aromatic hydrocarbon (PAH) contamination in urban runoff. Dietary exposure was to a mean concentration of 0, 3.5, 8.9, and 13 microg oil/g fish, and sampling took place after 3, 7, 11, and 15 weeks. The accumulation of compounds in muscle tissue, the elimination of bile metabolites, the activity of 7-ethoxyresorufin O-deethylase (EROD) in liver, and morphometric variables were compared at the different concentrations and times of sampling. The concentration of fluorescing compounds in muscle displayed the best dose- and time-response pattern, whereas other biological, chemical, and biochemical responses were not as well defined. No correlation could be drawn between the concentration of PAH in the oil and the measured variables. The environmentally relevant concentrations used in the experiment show the importance of choosing broad and specific indicators of exposure in a multidisciplinary investigation and the need for further research in chemical and toxicologic areas

  3. Fewer Doses of HPV Vaccine Result in Immune Response Similar to Three-Dose Regimen

    Science.gov (United States)

    ... Note Fewer doses of HPV vaccine result in immune response similar to three-dose regimen Posted: November 4, ... or three doses of Cervarix. They also measured immune responses of unvaccinated women who, at enrollment, were found ...

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

    Science.gov (United States)

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

    2013-09-01

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

  5. 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 analy......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...... women, 25 men, mean age 25.6 years ( range 18 - 40 years)) completed the study. Intervention: The volunteers were randomly assigned into five groups receiving either placebo or a mixture of the two probiotics in the concentration of 10(8), 10(9), 10(10) or 10(11) CFU/day in 2 weeks run-in period, 3...

  6. Dose-response relationship of nasopharyngeal carcinoma above conventional tumoricidal level: A study by the Hong Kong nasopharyngeal carcinoma study group (HKNPCSG)

    International Nuclear Information System (INIS)

    Teo, Peter M.L.; Leung, S.F.; Tung, Stewart Y.; Zee, Benny; Sham, Jonathan S.T.; Lee, Anne W.M.; Lau, W.H.; Kwan, W.H.; Leung, T.W.; Chua, Daniel; Sze, Wai Man; Au, Joseph S.K.; Yu, K.H.; O, Sai Ki; Kwong, Dora; Yau, T.K.; Law, Stephen C.K.; Sze, Wing Kin; Au, Gordon; Chan, Anthony T.C.

    2006-01-01

    Background and purpose: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. Patients and methods: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n=2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (≤40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. Results: On multivariate analysis, T-stage (P< 0.01; hazard ratio [HR], 1.58) and optimal boost (P=0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P=0.01; HR, 0.33); use of a boost (P<0.01; HR, 0.60) and age (P=0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. Conclusions: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity

  7. Effects of dose fractionation on the response of alanine dosimetry

    International Nuclear Information System (INIS)

    Lundahl, Brad; Logar, John; Desrosiers, Marc; Puhl, James

    2014-01-01

    Alanine dosimetry is well established as a transfer standard and is becoming more prevalently used in routine dosimetry systems for radiation processing. Many routine measurement applications in radiation processing involve absorbed dose measurements resulting from fractioned exposures to ionizing radiation. Fractioning of absorbed dose is identified as an influence quantity (ISO/ASTM, 2013). This paper reports on study results of absorbed dose fractioning characteristics of alanine for gamma and high energy electron beam radiation sources. The results of this study indicate a radiation response difference due to absorbed dose fractioning in response can be observed after four fractionations for high-energy electron beams and no difference up to seven fractions for gamma rays using an ANOVA evaluation method. - Highlights: • Fractioning effects signaled in electron beam using an ANOVA at 6 equal increments. • Fractioning effects not signaled in gamma using an ANOVA up to 7 equal increments. • Insensitivity of alanine to dose fractioning indicates nominal impact on calibration

  8. 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....

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  10. Shared Dosimetry Error in Epidemiological Dose-Response Analyses

    Energy Technology Data Exchange (ETDEWEB)

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

    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.

  11. 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.

  12. 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

  13. Shared dosimetry error in epidemiological dose-response analyses

    International Nuclear Information System (INIS)

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

    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

  14. Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study.

    Science.gov (United States)

    Rowe, K S; Rowe, K J

    1994-11-01

    To establish whether there is an association between the ingestion of synthetic food colorings and behavioral change in children referred for assessment of "hyperactivity." From approximately 800 children referred to the Royal Children's Hospital (Melbourne) for assessment of suspected hyperactivity, 200 were included in a 6-week open trial of a diet free of synthetic food coloring. The parents of 150 children reported behavioral improvement with the diet, and deterioration on the introduction of foods noted to contain synthetic coloring. A 30-item behavioral rating inventory was devised from an examination of the clinical histories of 50 suspected reactors. Thirty-four other children (23 suspected reactors, 11 uncertain reactors) and 20 control subjects, aged 2 to 14 years, were studied. A 21-day, double-blind, placebo-controlled, repeated-measures study used each child as his or her own control. Placebo, or one of six dose levels of tartrazine (1, 2, 5, 10, 20, 50 mg), was administered randomly each morning, and behavioral ratings were recorded by parents at the end of each 24 hours. The study identified 24 children as clear reactors (19 of 23 "suspected reactors," 3 of 11 "uncertain reactors," and 2 of 20 "control subjects"). They were irritable and restless and had sleep disturbance. Significant reactions were observed at all six dose levels. A dose response effect was obtained. With a dose increase greater than 10 mg, the duration of effect was prolonged. Behavioral changes in irritability, restlessness, and sleep disturbance are associated with the ingestion of tartrazine in some children. A dose response effect was observed.

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

    International Nuclear Information System (INIS)

    Benson, Blaine E.; Spyker, Daniel A.; Troutman, William G.; Watson, William A.

    2006-01-01

    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

  16. Aspirin as a potential modality for the chemoprevention of breast cancer: A dose-response meta-analysis of cohort studies from 857,831 participants.

    Science.gov (United States)

    Lu, Liming; Shi, Leiyu; Zeng, Jingchun; Wen, Zehuai

    2017-06-20

    Previous meta-analyses on the relationship between aspirin use and breast cancer risk have drawn inconsistent results. In addition, the threshold effect of different doses, frequencies and durations of aspirin use in preventing breast cancer have yet to be established. The search yielded 13 prospective cohort studies (N=857,831 participants) that reported an average of 7.6 cases/1,000 person-years of breast cancer during a follow-up period of from 4.4 to 14 years. With a random effects model, a borderline significant inverse association was observed between overall aspirin use and breast cancer risk, with a summarized RR = 0.94 (P = 0.051, 95% CI 0.87-1.01). The linear regression model was a better fit for the dose-response relationship, which displayed a potential relationship between the frequency of aspirin use and breast cancer risk (RR = 0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It was also a better fit for the duration of aspirin use and breast cancer risk (RR = 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use). We searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for relevant prospective cohort studies of aspirin use and breast cancer risk. Meta-analysis of relative risks (RR) estimates associated with aspirin intake were presented by fixed or random effects models. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression. Our study confirmed a dose-response relationship between aspirin use and breast cancer risk. For clinical prevention, long term (>5 years) consistent use (2-7 times/week) of aspirin appears to be more effective in achieving a protective effect against breast cancer.

  17. The effect of different doses of esmolol on hemodynamic, bispectral index and movement response during orotracheal intubation: prospective, randomized, double-blind study

    Directory of Open Access Journals (Sweden)

    Mensure Yılmaz Çakırgöz

    2014-12-01

    Full Text Available Objective: A prospective, randomized and double-blind study was planned to identify the optimum dose of esmolol infusion to suppress the increase in bispectral index values and the movement and hemodynamic responses to tracheal intubation. Materials and methods: One hundred and twenty patients were randomly allocated to one of three groups in a double-blind fashion. 2.5 mg kg-1 propofol was administered for anesthesia induction. After loss of consciousness, and before administration of 0.6 mg kg-1 rocuronium, a tourniquet was applied to one arm and inflated to 50 mm Hg greater than systolic pressure. The patients were divided into 3 groups; 1 mg kg-1 h-1 esmolol was given as the loading dose and in Group Es50 50 μg kg-1 min-1, in Group Es150 150 μg kg-1 min-1, and in Group Es250 250 μg kg-1 min-1 esmolol infusion was started. Five minutes after the esmolol has been begun, the trachea was intubated; gross movement within the first minute after orotracheal intubation was recorded. Results: Incidence of movement response and the ΔBIS max values were comparable in Group Es250 and Group Es150, but these values were significantly higher in Group Es50 than in the other two groups. In all three groups in the 1st minute after tracheal intubation heart rate and mean arterial pressure were significantly higher compared to values from before intubation (p < 0.05. In the study period there was no significant difference between the groups in terms of heart rate and mean arterial pressure. Conclusion: In clinical practise we believe that after 1 mg kg-1 loading dose, 150 μg kg-1 min-1 iv esmolol dose is sufficient to suppress responses to tracheal intubation without increasing side effects.

  18. CBF and CMRo2 during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

    International Nuclear Information System (INIS)

    Madsen, J.B.; Cold, G.E.; Eriksen, H.O.; Eskesen, V.; Blatt-Lyon, B.

    1986-01-01

    In 14 patients with supratentorial cerebral tumours with midline shift ≤ 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo 2 ) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety and Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In group 1 (n=7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRo 2 measured about 70 min after induction averaged 30.1 ml 100 g -1 min -1 and 1.98 ml O 2 100 g -1 min -1 , respectively. During the second CBF study 1 h later, CBF and CMRo 2 were unchanged (P>0.05). In group 2 (n=7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRo 2 was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRo 2 and suppression in the EEG activity, whereas CBF was unchanged (author)

  19. A 12-Month-Interval Dosing Study in Adults Indicates That a Single Dose of the National Institute of Allergy and Infectious Diseases Tetravalent Dengue Vaccine Induces a Robust Neutralizing Antibody Response.

    Science.gov (United States)

    Durbin, Anna P; Kirkpatrick, Beth D; Pierce, Kristen K; Carmolli, Marya P; Tibery, Cecilia M; Grier, Palmtama L; Hynes, Noreen; Opert, Kari; Jarvis, Adrienne P; Sabundayo, Beulah P; McElvany, Benjamin D; Sendra, Eli A; Larsson, Catherine J; Jo, Matthew; Lovchik, Janece M; Luke, Catherine J; Walsh, Mary C; Fraser, Ellen A; Subbarao, Kanta; Whitehead, Stephen S

    2016-09-15

    The ideal dengue vaccine will provide protection against all serotypes of dengue virus and will be economical and uncomplicated in its administration. To determine the ability of a single dose of the live attenuated tetravalent dengue vaccine TV003 to induce a suitable neutralizing antibody response, a placebo-controlled clinical trial was performed in 48 healthy adults who received 2 doses of vaccine or placebo administered 12 months apart. Evaluation of safety, vaccine viremia, and neutralizing antibody response after each dose indicated that the first dose of vaccine was capable of preventing infection with the second dose, thus indicating that multiple doses are unnecessary. NCT01782300. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  20. Response of cellulose nitrate track detectors to electron doses

    CERN Document Server

    Segovia, N; Moreno, A; Vazquez-Polo, G; Santamaría, T; Aranda, P; Hernández, A

    1999-01-01

    In order to study alternative dose determination methods, the bulk etching velocity and the latent track annealing of LR 115 track detectors was studied during electron irradiation runs from a Pelletron accelerator. For this purpose alpha irradiated and blank detectors were exposed to increasing electron doses from 10.5 to 317.5 kGy. After the irradiation with electrons the detectors were etched under routine conditions, except for the etching time, that was varied for each electron dose in order to reach a fixed residual thickness. The variation of the bulk etching velocity as a function of each one of the electron doses supplied, was interpolated in order to obtain dosimetric response curves. The observed annealing effect on the latent tracks is discussed as a function of the total electron doses supplied and the temperature.

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

    Science.gov (United States)

    Benson, Blaine E; Spyker, Daniel A; Troutman, William G; Watson, William A

    2006-06-01

    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. 3,458 single-substance clonidine exposures in children 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) microg/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). The logistic model describing medical outcome (P TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures.

  2. A multistep therapy with subcutaneous low dose recombinant interleukin-2, 5-fluorouracil and leucovorin prolongs the response of metastatic colorectal cancer patients: a pilot study.

    Science.gov (United States)

    Nicolini, A; Carpi, A; Ferrari, P; Sagripanti, A; Anselmi, L

    1998-01-01

    Data from 12 metastatic colorectal cancer patients who were submitted to a pilot study with a multistep subcutaneous (sc) low dose recombinant interleukin-2 (rIL-2), 5-fluorouracil (5-FU) and leucovorin (LV) administration were compared with those from 13 historical controls who were comparable for the major prognostic indices. All 12 patients in the pilot study were subjected initially to six to eight courses of 5-FU-LV by endovenous (ev) bolus consistent with the Machover schedule alternating with 6 weeks of rIL-2 cycles. At the progression of metastatic disease, the patients were given 500 mg/m2 per day of 5-FU by continuous infusion (ci) for 5 days every 4 weeks and in case of further progression, 2,600 mg/m2 of 5-FU by 24-h ci once a week for 6 weeks. The control patients were treated with 5-FU-LV by the Machover schedule until progression and then observed. As yet, two patients in the pilot study and three control patients are currently alive. In the pilot study, the patients' response rate (CR + PR) and overall response rate (CR + PR + SD) were much higher than in the controls (50 vs 23% and 92 vs 54%, respectively). Time duration of response and survival from primary surgery were more prolonged in the pilot study than in the historical control, although not significantly (10.5 vs 6 and 41.5 vs 29 months, respectively). Time from starting therapy to progression and survival from relapse were significantly in favour of the pilot study (11.5 vs 4 and 31 vs 13.5 months; P < 0.01 and P < 0.05 unpaired t-test, respectively). Low dose s.c. rIL-2 cycles were well tolerated and no interruption occurred. In the pilot study sporadic grade 3 toxicity (diarrhoea or leucopenia) was responsible for the reduction of 5-FU doses to 80% of the previous infusion, but no treatment was postponed. In conclusion, these preliminary data suggest the opportunity to initiate large prospective randomized trials using a multistep therapy with rIL-2, 5-FU ci at conventional and at high

  3. Minoxidil dose response study in female pattern hair loss patients determined to be non-responders to 5% topical minoxidil.

    Science.gov (United States)

    McCoy, J; Goren, A; Kovacevic, M; Shapiro, J

    2016-01-01

    Topical minoxidil is the only US FDA approved drug for the treatment of female pattern hair loss (FPHL). 5% minoxidil foam is only effective at re-growing hair in a minority of women (approximately 40%). Thus, the majority of FPHL patients remain untreated. Previously, we demonstrated that nonresponders to 5% minoxidil have low metabolism of minoxidil in hair follicles. As such, we hypothesized that increasing the dosage of topical minoxidil to low metabolizers would increase the number of responders without increasing the incidence of adverse events. In this study, we recruited FPHL subjects that were identified as non-responders to 5% topical minoxidil utilizing the previously validated assay for minoxidil response. Subjects were treated for 12 weeks with a novel 15% topical minoxidil solution. At 12 weeks, 60% of subjects achieved a clinically significant response based on target area hair counts (>13.7% from baseline), as well as significant improvement in global photographic assessment. None of the subjects experienced significant hemodynamic changes or any other adverse events. To the best of our knowledge, this is the first study to demonstrate the potentially beneficial effect of a higher dosage of minoxidil in FPHL subjects who fail to respond to 5% minoxidil.

  4. Dose-response association of screen time-based sedentary behaviour in children and adolescents and depression: a meta-analysis of observational studies.

    Science.gov (United States)

    Liu, Mingli; Wu, Lang; Yao, Shuqiao

    2016-10-01

    Depression represents a growing public health burden. Understanding how screen time (ST) in juveniles may be associated with risk of depression is critical for the development of prevention and intervention strategies. Findings from studies addressing this question thus far have been inconsistent. Therefore, we conducted a comprehensive systematic review and meta-analysis of data related to this question. The meta-analysis was conducted in accordance with the PRISMA guideline. We searched the electronic databases of PubMed, Web of Science and EBSCO systematically (up to 6 May 2015). OR was adopted as the pooled measurement of association between ST and depression risk. Dose-response was estimated by a generalised least squares trend estimation. Twelve cross-sectional studies and four longitudinal studies (including 1 cohort study) involving a total of 127 714 participants were included. Overall, higher ST in preadolescent children and adolescents was significantly associated with a higher risk of depression (OR=1.12; 95% CI 1.03 to 1.22). Screen type, age, population and reference category acted as significant moderators. Compared with the reference group who had no ST, there was a non-linear dose-response association of ST with a decreasing risk of depression at ST<2 h/day, with the lowest risk being observed for 1 h/day (OR=0.88; 95% CI 0.84 to 0.93). Our meta-analysis suggests that ST in children and adolescents is associated with depression risk in a non-linear dose-response manner. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Design of radiation dose tumor response assays

    International Nuclear Information System (INIS)

    Suit, H.D.; Hwang, T.; Hsieh, C.; Thames, H.

    1985-01-01

    The efficient utilization of animals in a radiation dose response assay for tumor control requires a definition of the goal, e.g., TCD50 or slope. A series of computer modelled ''experiments'' have been performed for each of a number of allocations of dose levels (DL) and number of animals/DL. The authors stipulated that the assumed TCD50 was .85 of true value; assumed slope was correct. They stipulated a binominal distribution of observed tumor control results at each dose level. A pilot assay used 6 tumors at 7 DL (from TCD1-TCD97). The second assay used 30 tumors assigned to 2,3,5 or 9 DL and to selected tumor control probabilities (TCP derived from the pilot run. Results from 100 test runs were combined with the pilot run for each of the combination of DL and TCP values. Logit regression lines were fitted through these ''data'' and the 95% CL around the TCD50 and the TCD37 values and the variances of the slopes were computed. These experiments were repeated using the method suggested by Porter (1980). Results show that a different strategy is needed depending upon the goal, viz. TCD50 or TCD37 vs slope. The differences between the two approaches are discussed

  6. Determination of tolerance dose uncertainties and optimal design of dose response experiments with small animal numbers

    International Nuclear Information System (INIS)

    Karger, C.P.; Hartmann, G.H.

    2001-01-01

    Background: Dose response experiments aim to determine the complication probability as a function of dose. Adjusting the parameters of the frequently used dose response model P(D)=1/[1+(D 50 /D) k ] to the experimental data, 2 intuitive quantities are obtained: The tolerance dose D 50 and the slope parameter k. For mathematical reasons, however, standard statistic software uses a different set of parameters. Therefore, the resulting fit parameters of the statistic software as well as their standard errors have to be transformed to obtain D 50 and k as well as their standard errors. Material and Methods: The influence of the number of dose levels on the uncertainty of the fit parameters is studied by a simulation for a fixed number of animals. For experiments with small animal numbers, statistical artifacts may prevent the determination of the standard errors of the fit parameters. Consequences on the design of dose response experiments are investigated. Results: Explicit formulas are presented, which allow to calculate the parameters D 50 and k as well as their standard errors from the output of standard statistic software. The simulation shows, that the standard errors of the resulting parameters are independent of the number of dose levels, as long as the total number of animals involved in the experiment, remains constant. Conclusion: Statistical artifacts in experiments containing small animal numbers may be prevented by an adequate design of the experiment. For this, it is suggested to select a higher number of dose levels, rather than using a higher number of animals per dose level. (orig.) [de

  7. Controlled Optimal Design Program for the Logit Dose Response Model

    Directory of Open Access Journals (Sweden)

    Jiaqiao Hu

    2010-10-01

    Full Text Available The assessment of dose-response is an integral component of the drug development process. Parallel dose-response studies are conducted, customarily, in preclinical and phase 1, 2 clinical trials for this purpose. Practical constraints on dose range, dose levels and dose proportions are intrinsic issues in the design of dose response studies because of drug toxicity, efficacy, FDA regulations, protocol requirements, clinical trial logistics, and marketing issues. We provide a free on-line software package called Controlled Optimal Design 2.0 for generating controlled optimal designs that can incorporate prior information and multiple objectives, and meet multiple practical constraints at the same time. Researchers can either run the web-based design program or download its stand-alone version to construct the desired multiple-objective controlled Bayesian optimal designs. Because researchers often adopt ad-hoc design schemes such as the equal allocation rules without knowing how efficient such designs would be for the design problem, the program also evaluates the efficiency of user-supplied designs.

  8. SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

    Energy Technology Data Exchange (ETDEWEB)

    Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C [The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom)

    2014-06-01

    Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

  9. Effect of low dose radiation in lymphocytes from children exposed to ionizing radiation after the Chernobyl accident. Cytogenetic, chromosome painting, GPA and adaptive response studies

    International Nuclear Information System (INIS)

    Padovani, L.; Appolloni, M.; Anzidei, P.; Spano, M.; Stronati, L.; Testa, A.; Mauro, F.

    1997-01-01

    The present study concerns the monitoring of some children coming from Byelorussian, Ukrainian and Russian republics, exposed to the fall-out, or to the initial acute dose of radiation with the aim of assessing the effects of ionizing radiation on human health and of verifying the persisting of chromosomal damage several years after the accident. Both structural chromosomes damage (conventional cytogenetic and chromosome painting) and molecular mutation (GPA) have been investigated, moreover the possible induction of an adaptive response has been tested. (author)

  10. Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

    Science.gov (United States)

    Rini, B I; Melichar, B; Fishman, M N; Oya, M; Pithavala, Y K; Chen, Y; Bair, A H; Grünwald, V

    2015-07-01

    In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical

  11. MONTEC, an interactive fortran program to simulate radiation dose and dose-rate responses of populations

    International Nuclear Information System (INIS)

    Perry, K.A.; Szekely, J.G.

    1983-09-01

    The computer program MONTEC was written to simulate the distribution of responses in a population whose members are exposed to multiple radiation doses at variable dose rates. These doses and dose rates are randomly selected from lognormal distributions. The individual radiation responses are calculated from three equations, which include dose and dose-rate terms. Other response-dose/rate relationships or distributions can be incorporated by the user as the need arises. The purpose of this documentation is to provide a complete operating manual for the program. This version is written in FORTRAN-10 for the DEC system PDP-10

  12. Dose-response relationship in local radiotherapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  13. Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects

    Energy Technology Data Exchange (ETDEWEB)

    Inskip, Peter D., E-mail: inskippeter@gmail.com [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Sigurdson, Alice J.; Veiga, Lene [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bhatti, Parveen [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Ronckers, Cécile [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Rajaraman, Preetha [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Boukheris, Houda [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); The University of Oran School of Medicine (Algeria); Stovall, Marilyn; Smith, Susan [Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States); Hammond, Sue [Department of Laboratory Medicine and Pathology, Children' s Hospital and Ohio State University College of Medicine, Columbus, Ohio (United States); Henderson, Tara O. [University of Chicago Department of Pediatrics, Section of Hematology, Oncology and Stem Cell Transplantation, Chicago, Illinois (United States); and others

    2016-03-15

    Objectives: The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose–response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. Methods: This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site–specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). Results: Linear dose–response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. Conclusions: The results suggest that the effect of high-dose irradiation is consistent with a linear dose–response for most organs, but they also reveal important organ-specific and host

  14. Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects

    International Nuclear Information System (INIS)

    Inskip, Peter D.; Sigurdson, Alice J.; Veiga, Lene; Bhatti, Parveen; Ronckers, Cécile; Rajaraman, Preetha; Boukheris, Houda; Stovall, Marilyn; Smith, Susan; Hammond, Sue; Henderson, Tara O.

    2016-01-01

    Objectives: The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose–response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. Methods: This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site–specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). Results: Linear dose–response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. Conclusions: The results suggest that the effect of high-dose irradiation is consistent with a linear dose–response for most organs, but they also reveal important organ-specific and host

  15. 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...

  16. A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization

    DEFF Research Database (Denmark)

    Loft, A; Egeberg, Anne Noes; Smitz, J

    2012-01-01

    Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? SUMMARY ANSWER: Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses...... of hCG up to 150 IU are compatible with good live birth rates. A ceiling level of estradiol (E(2)) was reached with hCG doses above 100 IU/day. A positive dose-response was seen for pre-ovulatory progesterone, but concentrations remained below values for which an impairment of endometrial receptivity...... low doses of hCG were associated with FSH. We analysed the clinical, embryological and endocrine aspects of adding increasing doses of hCG to rFSH from the first day of stimulation for IVF....

  17. Physical activity and incident type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Smith, Andrea D; Crippa, Alessio; Woodcock, James; Brage, Søren

    2016-12-01

    Inverse associations between physical activity (PA) and type 2 diabetes mellitus are well known. However, the shape of the dose-response relationship is still uncertain. This review synthesises results from longitudinal studies in general populations and uses non-linear models of the association between PA and incident type 2 diabetes. A systematic literature search identified 28 prospective studies on leisure-time PA (LTPA) or total PA and risk of type 2 diabetes. PA exposures were converted into metabolic equivalent of task (MET) h/week and marginal MET (MMET) h/week, a measure only considering energy expended above resting metabolic rate. Restricted cubic splines were used to model the exposure-disease relationship. Our results suggest an overall non-linear relationship; using the cubic spline model we found a risk reduction of 26% (95% CI 20%, 31%) for type 2 diabetes among those who achieved 11.25 MET h/week (equivalent to 150 min/week of moderate activity) relative to inactive individuals. Achieving twice this amount of PA was associated with a risk reduction of 36% (95% CI 27%, 46%), with further reductions at higher doses (60 MET h/week, risk reduction of 53%). Results for the MMET h/week dose-response curve were similar for moderate intensity PA, but benefits were greater for higher intensity PA and smaller for lower intensity activity. Higher levels of LTPA were associated with substantially lower incidence of type 2 diabetes in the general population. The relationship between LTPA and type 2 diabetes was curvilinear; the greatest relative benefits are achieved at low levels of activity, but additional benefits can be realised at exposures considerably higher than those prescribed by public health recommendations.

  18. The Radiation Dose-Response of the Human Spinal Cord

    International Nuclear Information System (INIS)

    Schultheiss, Timothy E.

    2008-01-01

    Purpose: To characterize the radiation dose-response of the human spinal cord. Methods and Materials: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and α/β ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. Results: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The α/β = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. Conclusions: The estimate of α/β is smaller than usually quoted, but values this small were found in some studies. Using α/β = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation

  19. DNA vaccination of rainbow trout against viral hemorrhagic septicemia virus: A dose-response and time-course study

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Einer-Jensen, Katja; Martinussen, T.

    2000-01-01

    Viral hemorrhagic septicemia (VHS) in rainbow trout Oncorhynchus mykiss is caused by VHS virus (VHSV), which belongs to the rhabdovirus family. Among the different strategies for immunizing fish with a recombinant vaccine, genetic immunization has recently proven to be highly effective. To further...... investigate the potential for protecting fish against VHS by DNA vaccination, experiments were conducted to determine the amount of plasmid DNA needed for induction of protective immunity. The time to onset of immunity and the duration of protection following administration of a protective vaccine dose were...... serologically different from the isolate used for vaccine development. Following administration of 1 mug of a DNA vaccine, significant protection against VHS was observed in the fish as early as 8 d postvaccination. At 168 d postvaccination, the fish had increased in size by a factor of 10 and protection...

  20. Harderian Gland Tumorigenesis: Low-Dose and LET Response

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2016-04-19

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  1. The Reproducibility of Blood Acid Base Responses in Male Collegiate Athletes Following Individualised Doses of Sodium Bicarbonate: A Randomised Controlled Crossover Study.

    Science.gov (United States)

    Gough, Lewis A; Deb, Sanjoy K; Sparks, Andy S; McNaughton, Lars R

    2017-10-01

    Current evidence suggests sodium bicarbonate (NaHCO 3 ) should be ingested based upon the individualised alkalotic peak of either blood pH or bicarbonate (HCO 3 - ) because of large inter-individual variations (10-180 min). If such a strategy is to be practical, the blood analyte response needs to be reproducible. This study aimed to evaluate the degree of reproducibility of both time to peak (TTP) and absolute change in blood pH, HCO 3 - and sodium (Na + ) following acute NaHCO 3 ingestion. Male participants (n = 15) with backgrounds in rugby, football or sprinting completed six randomised treatments entailing ingestion of two doses of 0.2 g·kg -1 body mass (BM) NaHCO 3 (SBC2a and b), two doses of 0.3 g·kg -1 BM NaHCO 3 (SBC3a and b) or two control treatments (CON1a and b) on separate days. Blood analysis included pH, HCO 3 - and Na + prior to and at regular time points following NaHCO 3 ingestion over a 3-h period. HCO 3 - displayed greater reproducibility than pH in intraclass correlation coefficient (ICC) analysis for both TTP (HCO 3 - SBC2 r = 0.77, P = 0.003; SBC3 r = 0.94, P based on HCO 3 - responses and evaluate effects on exercise performance.

  2. 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".

  3. Coffee intake and the incident risk of cognitive disorders: A dose-response meta-analysis of nine prospective cohort studies.

    Science.gov (United States)

    Wu, Lei; Sun, Dali; He, Yao

    2017-06-01

    Previous epidemiological studies have provided inconsistent conclusions on the impact of coffee consumption in the developing of cognitive disorders. However, no previous meta-analysis has pooled the evidence from the prospective cohort studies to assess the influence of coffee drinking and its potential dose-response patterns on the risk of developing cognitive disorders specifically. Two databases (PubMed and Embase) were searched for evidence of cohort studies from inception to February 2016. We used a generic inverse-variance method with a random-effects model to pool the fully adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). In the dose-response analyses, a generalized least-squares trend estimation model was applied to computing the study-specific slopes. Nine prospective cohort studies involving 34,282 participants were included in our study. The duration of follow-up years ranged from 1.3 to 28. Compared with coffee was inversely linked with the occurrence of cognitive disorders (i.e., Alzheimer's disease, dementia, cognitive decline, and cognitive impairment), and the pooled RR (95% CI) was 0.82 (0.71, 0.94) with evidence of non-significant heterogeneity (I 2  = 25%). Non-significant differences were presented for the association between coffee consumption (>3 vs. coffee consumption. A "J-shaped" association was presented between coffee intake and incident cognitive disorders, with the lowest risk of incident cognitive disorders at a daily consumption level of 1-2 cups of coffee. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  4. Dose-rate dependence of thermoluminescence response

    International Nuclear Information System (INIS)

    McKeever, S.W.S.; Chen, R.; Groom, P.J.; Durrani, S.A.

    1980-01-01

    The previously observed dose-rate effect of thermoluminescence in quartz at high dose-rates is given at theoretical formulation. Computer calculations simulating the experimental conditions yield similar results to the experimental ones. (orig.)

  5. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A; Gijsbers, Lieke; Givens, David I; Soedamah-Muthu, Sabita S

    2017-04-01

    With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up to September 2016. Random-effect meta-analyses with summarised dose-response data were performed for total (high-fat/low-fat) dairy, milk, fermented dairy, cheese and yogurt. Non-linear associations were investigated using the spine models and heterogeneity by subgroup analyses. A total of 29 cohort studies were available for meta-analysis, with 938,465 participants and 93,158 mortality, 28,419 CHD and 25,416 CVD cases. No associations were found for total (high-fat/low-fat) dairy, and milk with the health outcomes of mortality, CHD or CVD. Inverse associations were found between total fermented dairy (included sour milk products, cheese or yogurt; per 20 g/day) with mortality (RR 0.98, 95% CI 0.97-0.99; I 2  = 94.4%) and CVD risk (RR 0.98, 95% CI 0.97-0.99; I 2  = 87.5%). Further analyses of individual fermented dairy of cheese and yogurt showed cheese to have a 2% lower risk of CVD (RR 0.98, 95% CI 0.95-1.00; I 2  = 82.6%) per 10 g/day, but not yogurt. All of these marginally inverse associations of totally fermented dairy and cheese were attenuated in sensitivity analyses by removing one large Swedish study. This meta-analysis combining data from 29 prospective cohort studies demonstrated neutral associations between dairy products and cardiovascular and all-cause mortality. For future studies it is important to investigate in more detail how dairy products can be replaced by other foods.

  6. Changing Therapeutic Paradigms: Predicting mCRC Lesion Response to Selective Internal Radionuclide Therapy (SIRT based on Critical Absorbed Dose Thresholds: A Case Study

    Directory of Open Access Journals (Sweden)

    Kathy W

    2017-01-01

    Full Text Available A 65 year old male with metastatic colorectal cancer (mCRC in the liver was referred for selective internal radionuclide therapy (SIRT following a history of extensive systemic chemotherapy. 90Y PET imaging was performed immediately after treatment and used to confirm lesion targeting and measure individual lesion absorbed doses. Lesion dosimetry was highly predictive of eventual response in the follow-up FDG PET performed 8 weeks after therapy. The derived radiation dose map was used to plan a second SIRT procedure aiming to protect healthy liver by keeping absorbed dose below the critical dose threshold, whilst targeting the remaining lesions that had received sub-critical dosing. Again, 90Y PET was performed immediately post-treatment and used to derive absorbed dose measures to both lesions and healthy parenchyma. Additional followup FDG PET imaging again confirmed the role of the 90Y PET dose map as an early predictor of response, and a tool for safe repeat treatment planning.

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

    Science.gov (United States)

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

    2017-05-05

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

  8. Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Chen, Ling-Wei; Wu, Yi; Neelakantan, Nithya; Chong, Mary Foong-Fong; Pan, An; van Dam, Rob M

    2016-05-01

    To assess the association between maternal caffeine intake and risk of pregnancy loss using a systematic review and meta-analysis. Categorical and dose-response meta-analysis of prospective studies. Relevant articles were identified by searching MEDLINE and SCOPUS databases through 30 January 2015. Two authors independently extracted information from eligible studies. Random-effects models were used to derive the summary relative risks (RR) and corresponding 95% CI for specific categories of caffeine consumption and for a continuous association using generalized least-squares trend estimation. A total of 130 456 participants and 3429 cases in fourteen included studies. Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of pregnancy loss was 1·02 (0·85, 1·24; I(2)=28·3%) for low intake (50-149 mg/d), 1·16 (0·94, 1·41; I 2=49·6%) for moderate intake (150-349 mg/d), 1·40 (1·16, 1·68; I(2)=18·6%) for high intake (350-699 mg/d) and 1·72 (1·40, 2·13; I(2)=0·0%) for very high intake (≥ 700 mg/d). In the dose-response analysis, each 100 mg/d increment in maternal caffeine intake (~1 cup of coffee) was associated with 7% (95% CI 3%, 12%) higher risk of pregnancy loss. Our results may have been affected by publication bias, but the association remained significant for the subset of larger studies. Furthermore, adjustment for smoking and pregnancy symptoms may have been incomplete, potentially resulting in residual confounding. Albeit inconclusive, higher maternal caffeine intake was associated with a higher risk of pregnancy loss and adherence to guidelines to avoid high caffeine intake during pregnancy appears prudent.

  9. Radiotherapy for esophageal carcinoma: dose, response and survival

    Directory of Open Access Journals (Sweden)

    Luo Y

    2017-12-01

    Full Text Available Yijun Luo,1,* Qingfeng Mao,2,3,* Xiaoli Wang,1 Jinming Yu,3 Minghuan Li3 1Department of Oncology, The People’s Hospital of Jiangxi, Nanchang, 2School of Medical and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 3Department of Radiation Oncology and Radiology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China *These authors contributed equally to this work Abstract: Esophageal cancer (EC is an extremely aggressive, lethal malignancy that is increasing in incidence worldwide. At present, definitive chemoradiotherapy is accepted as the standard treatment for locally advanced EC. The EC guidelines recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes for patients who have received standard-dose radiotherapy remain unsatisfactory. However, some studies indicate that a higher radiation dose could improve local tumor control, and may also confer survival benefits. Some studies, however, suggest that high-dose radiotherapy does not bring survival benefit. The available data show that most failures occurred in the gross target volume (especially in the primary tumor after definitive chemoradiation. Based on those studies, we hypothesize that at least for some patients, more intense local therapy may lead to better local control and survival. The aim of this review is to evaluate the radiation dose, fractionation strategies, and predictive factors of response to therapy in functional imaging for definitive chemoradiotherapy in esophageal carcinoma, with an emphasis on seeking the predictive model of response to CRT and trying to individualize the radiation dose for EC patients. Keywords: esophageal cancer, radiation dose, altered fractionation, predictive factors, individualization 

  10. A dose-response study in mice of a tetravalent vaccine candidate composed of domain III-capsid proteins from dengue viruses.

    Science.gov (United States)

    Valdés, Iris; Marcos, Ernesto; Suzarte, Edith; Pérez, Yusleidi; Brown, Enma; Lazo, Laura; Cobas, Karem; Yaugel, Melyssa; Rodríguez, Yadira; Gil, Lázaro; Guillén, Gerardo; Hermida, Lisset

    2017-08-01

    Tetra DIIIC is a subunit vaccine candidate based on domain III of the envelope protein and the capsid protein of the four serotypes of dengue virus. This vaccine preparation contains the DIIIC proteins aggregated with a specific immunostimulatory oligodeoxynucleotide (ODN 39M). Tetra DIIIC has already been shown to be immunogenic and protective in mice and monkeys. In this study, we evaluated the immunogenicity in mice of several formulations of Tetra DIIIC containing different amounts of the recombinant proteins. The Tetra DIIIC formulation induced a humoral immune response against the four DENV serotypes, even at the lowest dose assayed. In contrast, the highest level of cell-mediated immunity, measured as frequency of IFNγ-producing cells, was detected in animals immunized with the lowest dose. The protective capacity of the tetravalent formulations was assessed using the mouse model of dengue virus encephalitis. Upon challenge, vaccinated mice showed significantly reduced virus replication in all tested groups. This study provides new information about the functionality of Tetra DIIIC as a vaccine candidate and also supports the crucial role of cell-mediated immunity in protection against dengue virus.

  11. TL response of citrine samples for high-dose dosimetry

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2011-01-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the thermoluminescence technique (TL). In this work, the TL properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tectosilicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The citrine stone samples were powdered, and the selected grains were mixed with Teflon in the proportion 2 (Teflon):1 (Citrine). The mixture was pressed and sintered for production of Citrine -Teflon pellets of 50 mg. The TL emission curve showed two peaks at 160 deg C and 220 deg C. To remove the TL peak (160 deg C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The TL dose-response curve between 50 Gy and 100 kGy, the reproducibility of TL response and the lower detection dose were obtained. The preliminary results show that citrine may be useful for high-dose dosimetry. (author)

  12. Pharmacodynamic effects of steady-state fingolimod on antibody response in healthy volunteers: a 4-week, randomized, placebo-controlled, parallel-group, multiple-dose study.

    Science.gov (United States)

    Boulton, Craig; Meiser, Karin; David, Olivier J; Schmouder, Robert

    2012-12-01

    Fingolimod, a first-in-class oral sphingosine 1-phosphate receptor (S1PR) modulator, is approved in many countries for relapsing-remitting multiple sclerosis, at a once-daily 0.5-mg dose. A reduction in peripheral lymphocyte count is an expected consequence of the fingolimod mechanism of S1PR modulation. The authors investigated if this pharmacodynamic effect impacts humoral and cellular immunogenicity. In this double-blind, parallel-group, 4-week study, 72 healthy volunteers were randomized to steady state, fingolimod 0.5 mg, 1.25 mg, or to placebo. The authors compared T-cell dependent and independent responses to the neoantigens, keyhole limpet hemocyanin (KLH), and pneumococcal polysaccharides vaccine (PPV-23), respectively, and additionally recall antigen response (tetanus toxoid [TT]) and delayed-type hypersensitivity (DTH) to KLH, TT, and Candida albicans. Fingolimod caused mild to moderate decreases in anti-KLH and anti-PPV-23 IgG and IgM levels versus placebo. Responder rates were identical between placebo and 0.5-mg groups for anti-KLH IgG (both > 90%) and comparable for anti-PPV-23 IgG (55% and 41%, respectively). Fingolimod did not affect anti-TT immunogenicity, and DTH response did not differ between placebo and fingolimod 0.5-mg groups. Expectedly, lymphocyte count reduced substantially in the fingolimod groups versus placebo but reversed by study end. Fingolimod was well tolerated, and the observed safety profile was consistent with previous reports.

  13. Dose escalation with 3-D CRT in prostate cancer: five year dose responses and optimal treatment

    International Nuclear Information System (INIS)

    Hanks, Gerald; Hanlon, Alexandra; Pinover, Wayne; Hunt, Margie; Movsas, Benjamin; Schultheiss, Timothy

    1997-01-01

    Purpose: To report 5 yr dose responses in prostate cancer patients treated with 3D-CRT and describe optimal treatment based on dose response. Methods: Dose escalation was studied in 233 consecutive patients treated with 3D-CRT between 3/89 and 10/92. All surviving patients have >32 mo follow-up, the median follow-up is 55 mo. Estimated logistic cumulative distribution functions (logit response models) fit to 5 yr actuarial bNED outcome are reported for 3 dose groups in each of 3 pretreatment PSA groupings (10-19.9 ng/ml and 20+ ng/ml); no dose response is observed for patients with pretreatment PSA <10 ng/ml. Logit response models fit to 5 yr actuarial late morbidity rates (grade 2 GI, grade 2 GU, grade 3,4 GI) are also reported for 4 dose groups. Patients are treated with CT planned 4-field conformal technique where the PTV encompasses the CTV by 1.0 cm in all directions including the anterior rectal wall margin. Patients are followed at 6 mo intervals with PSA and DRE, and bNED failure is defined as PSA ≥1.5 ng/ml and rising on two consecutive measures. The Fox Chase modification of the LENT morbidity scale is used for GI morbidity including any blood transfusion and/or more than 2 coagulations as a grade 3 event. GU morbidity follows the RTOG scale. Results: The logit response models based on 5 yr bNED results have slopes of 27% and 18% for pretreatment PSA grouping 10-19.9 ng/ml and 20+ ng/ml, respectively. The 50% bNED response is observed at 71 Gy and 80 Gy respectively, while the 80% bNED response is observed at 76 Gy for the 10-19.9 ng/ml group and estimated at 88 Gy for the 20+ ng/ml group. Logit dose response models for grade 2 GI and grade 2 GU morbidity show markedly different slopes, 23% versus 4%, respectively. The slope for grade 3,4 GI is 12%. The dose response model indicates grade 3,4 GI complication rates at 5 yrs are 8% at 76 Gy and 12% at 80 Gy. Conclusion: Based on 5 yr results, we can draw some conclusions about appropriate dose from these

  14. 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.

  15. Mahalanobis distance and variable selection to optimize dose response

    International Nuclear Information System (INIS)

    Moore, D.H. II; Bennett, D.E.; Wyrobek, A.J.; Kranzler, D.

    1979-01-01

    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

  16. A pilot double-blind randomised placebo-controlled dose-response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol.

    Science.gov (United States)

    Fernando, Shavi; Osianlis, Tiki; Vollenhoven, Beverley; Wallace, Euan; Rombauts, Luk

    2014-09-01

    High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation (IVF). Recent studies have reported that melatonin, a neurohormone secreted from the pineal gland in response to darkness, has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos. Early studies of oral melatonin (3-4 mg/day) in IVF have suggested favourable outcomes. However, most trials were poorly designed and none have addressed the optimum dose of melatonin. We present a proposal for a pilot double-blind randomised placebo-controlled dose-response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology. We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2 mg twice per day (n=40); melatonin 4 mg twice per day (n=40) and melatonin 8 mg twice per day (n=40). The primary outcome will be clinical pregnancy rate. Secondary clinical outcomes include oocyte number/quality, embryo number/quality and fertilisation rate. We will also measure serum melatonin and the oxidative stress marker, 8-hydroxy-2'-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up. We will investigate follicular blood flow with Doppler ultrasound, patient sleepiness scores and pregnancy complications, comparing outcomes between groups. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines. Ethical approval has been obtained from Monash Health HREC (Ref: 13402B), Monash University HREC (Ref: CF14/523-2014000181) and Monash Surgical Private Hospital HREC (Ref: 14107). Data analysis, interpretation and conclusions will be presented at national and international conferences and published in peer-reviewed journals. ACTRN12613001317785. Published by the BMJ Publishing Group Limited. For permission to use (where

  17. Leisure-time physical activity and incident metabolic syndrome: a systematic review and dose-response meta-analysis of cohort studies.

    Science.gov (United States)

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

    2017-10-01

    Leisure-time physical activity (LTPA) has been suggested to reduce risk of metabolic syndrome (MetS). However, a quantitative comprehensive assessment of the dose-response association between LTPA and incident MetS has not been reported. We performed a meta-analysis of studies assessing the risk of MetS with LTPA. MEDLINE via PubMed and EMBase databases were searched for relevant articles published up to March 13, 2017. Random-effects models were used to estimate the summary relative risk (RR) of MetS with LTPA. Restricted cubic splines were used to model the dose-response association. We identified 16 articles (18 studies including 76,699 participants and 13,871 cases of MetS). We found a negative linear association between LTPA and incident MetS, with a reduction of 8% in MetS risk per 10 metabolic equivalent of task (MET) h/week increment. According to the restricted cubic splines model, risk of MetS was reduced 10% with LTPA performed according to the basic guideline-recommended level of 150min of moderate PA (MPA) per week (10METh/week) versus inactivity (RR=0.90, 95% CI 0.86-0.94). It was reduced 20% and 53% with LTPA at twice (20METh/week) and seven times (70METh/week) the basic recommended level (RR=0.80, 95% CI 0.74-0.88 and 0.47, 95% CI 0.34-0.64, respectively). Our findings provide quantitative data suggesting that any amount of LTPA is better than none and that LTPA substantially exceeding the current LTPA guidelines is associated with an additional reduction in MetS risk. Copyright © 2017. Published by Elsevier Inc.

  18. Crohn's disease outpatients treated with adalimumab have an earlier secondary loss of response and requirement for dose escalation compared to infliximab: a real life cohort study.

    Science.gov (United States)

    Ma, Christopher; Huang, Vivian; Fedorak, Darryl K; Kroeker, Karen I; Dieleman, Levinus A; Halloran, Brendan P; Fedorak, Richard N

    2014-11-01

    The efficacy of anti-tumor necrosis factor alpha agents in maintaining remission in Crohn's disease may wane over time, leading to secondary loss of response that can often be overcome with dose escalation. Comparison of secondary loss of response of adalimumab and infliximab during long-term treatment of CD in a real-life IBD clinic has not been previously evaluated. A retrospective cohort study was conducted evaluating outpatients with CD on a maintenance regimen with adalimumab or infliximab from 200 to 2013 and who experienced a secondary loss of response. All infliximab-treated patients were anti-TNF naïve. Adalimumab-treated patients were stratified by prior anti-TNF exposure. Kaplan-Meier analysis was conducted to compare time to loss of response. 218 CD patients met inclusion criteria (117 infliximab, 101 adalimumab). Median follow-up duration was 170.0weeks for infliximab and 122.0weeks for adalimumab (p=0.61). The proportion of patients with secondary loss of response was similar for infliximab-treated - 51.3% (60/117) compared to adalimumab patients naïve to anti-TNF therapy - 60.5% (23/38) (p=0.32), and adalimumab patients with prior anti-TNF exposure - 65.1% (41/63) (p=0.08). Median time to secondary loss of response was longer for infliximab patients (99.3wk, IQR 55.7-168.5) compared to both adalimumab patients naïve to anti-TNF therapy (58.9wk, IQR 29.0-85.7) (p=0.03), and adalimumab patients with prior anti-TNF exposure (52.7wk, IQR 20.1-85.0) (p<0.001). Over 50% of CD patients treated with infliximab and adalimumab develop secondary loss of response. Time to loss of response was shorter in patients treated with adalimumab compared to those treated with infliximab. Prior anti-TNF exposure further accelerated time to loss of response. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  19. Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies

    NARCIS (Netherlands)

    Gijsbers, L.; Ding, E.L.; Malik, Vasanti; Goede, de J.; Geleijnse, J.M.; Soedamah-Muthu, S.S.

    2016-01-01

    BACKGROUND: A growing number of cohort studies suggest a potential role of dairy consumption in type 2 diabetes (T2D) prevention. The strength of this association and the amount of dairy needed is not clear. OBJECTIVE: We performed a meta-analysis to quantify the associations of incident T2D with

  20. Alcohol consumption and risk of atrial fibrillation: a prospective study and dose-response meta-analysis.

    Science.gov (United States)

    Larsson, Susanna C; Drca, Nikola; Wolk, Alicja

    2014-07-22

    Although high alcohol consumption has been associated with increased risk of atrial fibrillation (AF), the role of light to moderate drinking remains unclear. The study sought to investigate the association between alcohol consumption and AF risk in a prospective study of Swedish men and women and to conduct a meta-analysis of prospective studies to summarize available evidence. We followed 79,019 men and women who, at baseline, were free from AF and had completed a questionnaire about alcohol consumption and other risk factors for chronic diseases. Incident AF cases were ascertained by linkage to the Swedish Inpatient Register. For the meta-analysis, studies were identified by searching PubMed through January 10, 2014, and by reviewing references of pertinent publications. Study-specific relative risks (RRs) were combined using a random effects model. Over 859,420 person-years of follow-up (1998 to 2009), 7,245 incident AF cases were identified in our own cohort study. The association between alcohol consumption and AF did not differ by sex (p for interaction = 0.74). Compared with current drinkers of drink/week (12 g alcohol/drink), the multivariable RRs of AF were 1.01 (95% confidence interval [CI]: 0.94 to 1.09) for 1 to 6 drinks/week, 1.07 (95% CI: 0.98 to 1.17) for 7 to 14 drinks/week, 1.14 (95% CI: 1.01 to 1.28) for 15 to 21 drinks/week, and 1.39 (95% CI: 1.22 to 1.58) for >21 drinks/week. Results were similar after excluding binge drinkers. In a meta-analysis of 7 prospective studies, including 12,554 AF cases, the RRs were 1.08 (95% CI: 1.06 to 1.10) for 1 drink/day, 1.17 (95% CI: 1.13 to 1.21) for 2 drinks/day, 1.26 (95% CI: 1.19 to 1.33) for 3 drinks/day, 1.36 (95% CI: 1.27 to 1.46) for 4 drinks/day, and 1.47 (95% CI: 1.34 to 1.61) for 5 drinks/day, compared with nondrinkers. These findings indicate that alcohol consumption, even at moderate intakes, is a risk factor for atrial fibrillation. Copyright © 2014 American College of Cardiology Foundation

  1. "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.

  2. Dose-Response Effect of Tualang Honey on Postprandial Antioxidant Activity and Oxidative Stress in Female Athletes: A Pilot Study.

    Science.gov (United States)

    Ahmad, Nur Syamsina; Abdul Aziz, Azlina; Kong, Kin Weng; Hamid, Mohamad Shariff A; Cheong, Jadeera Phaik Geok; Hamzah, Sareena Hanim

    2017-12-01

    Tualang honey (TH) contains antioxidants such as ascorbic acid, phenolic acids, and flavonoids that may be protective against oxidative stress of exercise. The aim of this study was to examine the postprandial antioxidant activity and oxidative stress after ingestion of high and low dosages of TH in female athletes. Twenty female athletes (aged 21.3 [2.1] years; body weight [BW] 54.1 [5.7] kg) were randomly assigned into two groups and consumed either 1.5 g/kg BW TH (high honey; HH; n = 10) or 0.75 g/kg BW TH (low honey; LH; n = 10). Blood sample was collected at fasting and at 0.5, 1, 2, and 3 h after TH consumption. Plasma was analyzed for total phenolic content (TPC), antioxidant activity (ferric reducing antioxidant power [FRAP]), and oxidative stress biomarkers (malondialdehyde [MDA] and reactive oxygen species [ROS]). The 3-h area under the curve (AUC) for MDA was significantly lower in the LH group compared with HH group, suggesting less oxidative stress in the LH group. However, the AUCs for TPC, FRAP, and ROS were not affected by the dosages. The concentrations of TPC and FRAP increased from baseline to 2 and 1 h after TH consumption, respectively, and concentrations returned toward baseline at 3 h in both LH and HH groups. MDA concentration significantly decreased (p antioxidant activity and suppressing oxidative stress in female athletes. The time-course effect of TH that provides optimal antioxidant activity and oxidative stress protection was between 1 and 2 h after its consumption.

  3. The dose-response relationship for UV-tumorigenesis

    International Nuclear Information System (INIS)

    Gruijl, F.R. de.

    1982-01-01

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

  4. Role of heme Oxygenase-1 in low dose Radioadaptive response

    Directory of Open Access Journals (Sweden)

    Lingzhi Bao

    2016-08-01

    Full Text Available Radioadaptive response (RAR is an important phenomenon induced by low dose radiation. However, the molecular mechanism of RAR is obscure. In this study, we focused on the possible role of heme oxygenase 1 (HO-1 in RAR. Consistent with previous studies, priming dose of X-ray radiation (1–10 cGy induced significant RAR in normal human skin fibroblasts (AG 1522 cells. Transcription and translation of HO-1 was up-regulated more than two fold by a priming dose of radiation (5 cGy. Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, could mimic priming dose of X-rays to induce RAR. Knocking down of HO-1 by transfection of HO-1 siRNA significantly attenuated RAR. Furthermore, the expression of HO-1 gene was modulated by the nuclear factor (erythroid-derived 2-like 2 (Nrf2, which translocated from cytoplasm to nucleus after priming dose radiation and enhance the antioxidant level of cells.

  5. The role of variability of dose in dose-response relationships for alpha emitting radionuclides

    International Nuclear Information System (INIS)

    Crawford-Brown, D.J.; Hofmann, W.

    1989-01-01

    Radiation protection requires predictions of the effects of radiation at low mean organ doses. Since epidemiological data are restricted to moderate to high doses, extrapolation functions must be developed. The present paper derives such a function from theoretical considerations of the ability of radiation to initiate, promote and kill cells. The resulting function, however, is unable to account for the continued increase in cancer incidence amongst uranium miners and 224 Ra cases at mean organ doses of several tens of grays. This failure is ascribed to the use of mean organ dose as an appropriate variable in dose-response equations. By an explicit incorporation of variability in cellular doses, the model developed here is shown to display the general features of the epidemiological data when model parameters are made consistent with findings from cellular radiobiology. This indicates that variability of cellular dose may play an essential role in determining the shape of epidemiologically based dose-response curves. (author)

  6. Dose-dependent response of FGF-2 for lymphangiogenesis

    OpenAIRE

    Chang, Lynn K.; Garcia-Cardeña, Guillermo; Farnebo, Filip; Fannon, Michael; Chen, Emy J.; Butterfield, Catherine; Moses, Marsha A.; Mulligan, Richard C.; Folkman, Judah; Kaipainen, Arja

    2004-01-01

    Spatio-temporal studies on the growth of capillary blood vessels and capillary lymphatic vessels in tissue remodeling have suggested that lymphangiogenesis is angiogenesis-dependent. We revisited this concept by using fibroblast growth factor 2 (FGF-2) (80 ng) to stimulate the growth of both vessel types in the mouse cornea. When we lowered the dose of FGF-2 in the cornea 6.4-fold (12.5 ng), the primary response was lymphangiogenic. Further investigation revealed that vascular endothelial gro...

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

    Science.gov (United States)

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

    2013-10-01

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

  8. Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

    Science.gov (United States)

    Aune, Dagfinn; Sen, Abhijit; Norat, Teresa; Janszky, Imre; Romundstad, Pål; Tonstad, Serena; Vatten, Lars J

    2016-02-16

    Obesity has been associated with increased risk of heart failure, but whether overweight also increases risk is unclear. It is also unclear whether abdominal adiposity is more strongly associated with heart failure risk than general adiposity. We conducted a systematic review and meta-analysis of prospective studies to clarify the strength and shape of the dose-response relationship between general and abdominal adiposity and the risk of heart failure. PubMed and Embase databases were searched up to October 10, 2014. Summary relative risks were calculated using random-effects models. A total of 28 studies (27 publications) were included. Twenty-three prospective studies with >15 905 incident cases among 647 388 participants were included in the analysis of body mass index and heart failure incidence, and 4 studies were included for heart failure mortality. The summary relative risk for a 5-unit increment in body mass index was 1.41 (95% confidence interval, 1.34-1.47; I(2)=83%) for heart failure incidence and 1.26 (95% confidence interval, 0.85-1.87; I(2)=95%) heart failure mortality. Although the test for nonlinearity was significant (Pfailure. © 2016 American Heart Association, Inc.

  9. Dose-dependent response of FGF-2 for lymphangiogenesis.

    Science.gov (United States)

    Chang, Lynn K; Garcia-Cardeña, Guillermo; Farnebo, Filip; Fannon, Michael; Chen, Emy J; Butterfield, Catherine; Moses, Marsha A; Mulligan, Richard C; Folkman, Judah; Kaipainen, Arja

    2004-08-10

    Spatio-temporal studies on the growth of capillary blood vessels and capillary lymphatic vessels in tissue remodeling have suggested that lymphangiogenesis is angiogenesis-dependent. We revisited this concept by using fibroblast growth factor 2 (FGF-2) (80 ng) to stimulate the growth of both vessel types in the mouse cornea. When we lowered the dose of FGF-2 in the cornea 6.4-fold (12.5 ng), the primary response was lymphangiogenic. Further investigation revealed that vascular endothelial growth factor-C and -D are required for this apparent lymphangiogenic property of FGF-2, and when the small amount of accompanying angiogenesis was completely suppressed, lymphangiogenesis remained unaffected. Our findings demonstrate that there is a dose-dependent response of FGF-2 for lymphangiogenesis, and lymphangiogenesis can occur in the absence of a preexisting or developing vascular bed, i.e., in the absence of angiogenesis, in the mouse cornea.

  10. Doses in mammography. Preliminary study

    International Nuclear Information System (INIS)

    Marquez P, F.; Acosta R, N.; Universidad Nacional Mayor de San Marcos, Lima; Benavente, T.; Universidad Nacional Mayor de San Marcos, Lima; Poma, M.

    2002-01-01

    Mammography is the most important method to detect lesions in the breast with this technique one can detect small tumours before clear clinical symptoms appear. Mammographic image of require high quality standards due that the extremely low contrast between the normal and pathological areas in the breast, eg.g., they have similar attenuation and absorption coefficient. The x-ray mammographic systems, used in this study are Senographe 500t and Senographe DMR, a detector with a RadCal ionization chambers calibrated to the qualities of mammographic x-ray beams, and a breast simulator that is a phantoms of polymethylmethacrylate (PMMA) of several thicknesses with the equivalence of 50% of the glandular tissue. The results obtained indicate that the values of doses at the entrance surface of a breast (DES) are greater the reference value 20 mGy to 5,0 cm of PMMA and the values of the mean glandular dose (MGD) exceed the reference value of 2,1 mGy for 5,1 cm of compressed thick breast. We consider that the values high of the EDS and MGD are due that the x-ray systems no meeting in good condition or for used of x-ray spectra no suitable, so is recommendable be carried out test of quality control to the x-ray systems and also realize studies, or characterize the of x-ray mammographic spectra

  11. An updated dose-response analysis in Hodgkin's disease

    International Nuclear Information System (INIS)

    Vijayakumar, Srinivasan; Myrianthopoulos, L.C.; University of Chicago Center for Radiation Therapy

    1992-01-01

    Although radiotherapy cures a very high percentage of early stage patients with Hodgkin's disease (HD), there is a controversial dichotomy in the dose recommendations believed necessary to achieve >95% local control: Whereas one school of thought is to administer 40-44 Gy, other reports claim equal results with about 36 Gy. It is also not clear what doses are required for various tumor cell burdens. The original recommendation of 40-44 Gy was derived from a retrospective analysis of in-field control of disease from mostly kilovoltage data 3 decades ago. However, there have been many advances in evaluation of the extent of the disease and in radiotherapy-practice since the 1960s. Many more dose-control studies have been published in recent years, necessitating a revisit to the dose-response question in HD. Here dose-control data from the 60s to the 90s are compiled, and the original and updated data are analyzed with the same statistical method to see any differences. Also was performed a similar analysis of dose-control information for subclinical disease, 6 cm disease. Whereas original analysis (1040 sites at risk) suggested 98% in-field control with 44 Gy, the re- analysis including modern megavoltage data (4117 sites at risk) shows that similar in-field control for subclinical disease and disease of 6 cm are, 32.4 Gy (1426 sites at risk), 36.9Gy (1005 sites at risk) and 37.4 Gy (98 sites at risk), respectively. Results of current updated analysis will provide in-field disease control probabilities for different disease burdens and can serve as a guide in deciding dose prescriptions for practising radiation oncologists. (author). 59 refs.; 3 figs.; 6 tabs

  12. Carbohydrates, glycemic index, glycemic load, and breast cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Schlesinger, Sabrina; Chan, Doris S M; Vingeliene, Snieguole; Vieira, Ana R; Abar, Leila; Polemiti, Elli; Stevens, Christophe A T; Greenwood, Darren C; Aune, Dagfinn; Norat, Teresa

    2017-06-01

    The investigation of dose-response associations between carbohydrate intake, glycemic index, glycemic load, and risk of breast cancer stratified by menopausal status, hormone receptor status, and body mass index (BMI) remains inconclusive. A systematic review and dose-response meta-analyses was conducted to investigate these associations. As part of the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, PubMed was searched up to May 2015 for relevant studies on these associations. Prospective studies reporting associations between carbohydrate intake, glycemic index, or glycemic load and breast cancer risk were included. Two investigators independently extracted data from included studies. Random-effects models were used to summarize relative risks (RRs) and 95%CIs. Heterogeneity between subgroups, including menopausal status, hormone receptor status, and BMI was explored using meta-regression. Nineteen publications were included. The summary RRs (95%CIs) for breast cancer were 1.04 (1.00-1.07) per 10 units/d for glycemic index, 1.01 (0.98-1.04) per 50 units/d for glycemic load, and 1.00 (0.96-1.05) per 50 g/d for carbohydrate intake. For glycemic index, the association appeared slightly stronger among postmenopausal women (summary RR per 10 units/d, 1.06; 95%CI, 1.02-1.10) than among premenopausal women, though the difference was not statistically significant (Pheterogeneity = 0.15). Glycemic load and carbohydrate intake were positively associated with breast cancer among postmenopausal women with estrogen-negative tumors (summary RR for glycemic load, 1.28; 95%CI, 1.08-1.52; and summary RR for carbohydrates, 1.13; 95%CI, 1.02-1.25). No differences in BMI were detected. Menopausal and hormone receptor status, but not BMI, might be potential influencing factors for the associations between carbohydrate intake, glycemic index, glycemic load, and breast cancer. © The Author(s) 2017. Published by Oxford University Press

  13. Comparative study of dose-response curve for chromosome aberrations induced in human lymphocytes by {sup 60}Co and X-Rays

    Energy Technology Data Exchange (ETDEWEB)

    Mendes, Mariana E.; Mendonça, Julyanne C.G.; Andrade, Aida M.G.; Silva, Laís M.; Hwang, Suy; Melo, Ana M.M.A.; Santos, Neide; Lima, Fabiana F., E-mail: mendes_sb@hotmail.com [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)

    2017-11-01

    Biodosimetry represents a biological marker to the estimation of health risks after accidental overexposure to ionizing radiation. Chromosomal dicentric in peripheral blood lymphocytes have been the most reliable biomarker of exposure to IR during the last several decades. This technique could be used to support physical dosimetry or when it is impossible to achieve it. A reliable measurement of the absorbed dose is critical for medical decision, including the assessment of long-term health consequences. The aim of this research is to compare dose-response curves for dicentric aberration induced in human lymphocytes by {sup 60}Co and X-Rays. For both quality of radiation, the samples were exposed to at least eight different absorbed doses. The X-rays with dose rate of 0,275 Gy/min at Laboratory of Metrology (CRCN/NE - PE - Brazil) and the second one was exposed to cobalt source with dose rate of 0.055 Gy/min ({sup 60}Co Gammacell 220) located at Department of Nuclear Energy (UFPE-DEN-BRASIL). Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. The frequencies of dicentrics were counted in more than 18.000 metaphases for this comparison. After that, all frequencies and distributions of dicentrics were tested to analyze their conformity with Poisson distribution and then each quality of radiation were used for build the calibration curves using Dose Estimate program. These results showed that both curves followed the Poisson distribution and coefficients of each one are: YX-rays = 0,0013 (± 0,0006) + 0,0271 (± 0,0086)⁎D + 0,0556(±0,0050))⁎D{sup 2} and Y{sub Co-60} = 0,0014 (± 0,0010) + 0,0081 (± 0,0073))⁎D + 0,0451 (± 0,0046))⁎D{sup 2} (Y = frequency of dicentrics and D = absorbed dose). It was expected that there was no significant difference between this two types of radiation because both were low LET. We believed that dose rate have been a principal factor to produce this

  14. Topics on study of low dose-effect relationship

    International Nuclear Information System (INIS)

    Yamada, Takeshi; Ohyama, Harumi

    1999-01-01

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

  15. Analysis of Transcriptomic Dose Response Data in the ...

    Science.gov (United States)

    Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment Slide presentation at the HESI-HEALTH Canada-McGill Workshop on Transcriptomic Dose Response Data in the Context of Chemical Risk Assessment

  16. Effect of radiation doses rate on SOS response induction in irradiated Escherichia coli Cells

    International Nuclear Information System (INIS)

    Cuetara Lugo, Elizabeth B.; Fuentes Lorenzo, Jorge L.; Almeida Varela, Eliseo; Prieto Miranda, Enrique F.; Sanchez Lamar, Angel; Llagostera Casal, Montserrat

    2005-01-01

    The present work is aimed to study the effect of radiation dose rate on the induction of SOS response in Escherichia coli cells. We measured the induction of sul A reporter gene in PQ-37 (SOS Chromotest) cells. Lead devises were built with different diameter and these were used for diminishing the dose rate of PX- -30M irradiator. Our results show that radiation doses rate significantly modifies the induction of SOS response. Induction factor increases proportionally to doses rate in Escherichia coli cells defective to nucleotide excision repair (uvrA), but not in wild type cells. We conclude that the dose rate affects the level of induction of SOS response

  17. 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

  18. Evaluation of dose–response relationship between smoking load and cardiopulmonary fitness in adult smokers: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    V.T. Lauria

    2017-03-01

    Full Text Available Objective: To evaluate the dose–response relationship between smoking load and cardiopulmonary fitness, as measured with cardiopulmonary exercise testing (CPET, in adult smokers free of respiratory diseases. Methods: After a complete clinical evaluation and spirometry, 95 adult smokers (35 men and 60 women underwent CPET on a treadmill. Results: The physiological responses during CPET showed lower cardiorespiratory fitness levels, regardless of smoking load, with a peak V′O2 lower than 100% of the expected value and a lower maximum heart rate. We observed a significant moderate negative correlation between smoking load and peak V′O2. The smoking load also presented a significant negative correlation with maximum heart rate(r = −0.36; p < 0.05, lactate threshold(r = −0.45; p < 0.05, and peak ventilation(r = −0.43; p < 0.05. However, a dose–response relationship between smoking load quartiles and cardiopulmonary fitness was not found comparing quartiles of smoking loads after adjustment for age, sex and cardiovascular risk. Conclusion: There appears to be no dose–response relationship between SL and cardiopulmonary fitness in adult smokers with preserved pulmonary function, after adjusting the analysis for age and cardiovascular risk. Our results suggest that smoking cessation might be useful as the primary strategy to prevent cardiopulmonary fitness decline in smokers, regardless of smoking load. Thus, even a very low dose of tobacco use must be avoided in preventive strategies focusing on becoming people more physically active and fit. Keywords: Smoking load, Cardiopulmonary exercise testing, Spirometry, Physical fitness, Tobacco use disorder

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

    Science.gov (United States)

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

    2013-11-01

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

  20. Methodology for Estimating Ingestion Dose for Emergency Response at SRS

    International Nuclear Information System (INIS)

    Simpkins, A.A.

    2003-01-01

    At the Savannah River Site (SRS), emergency response computer models are used to estimate dose following releases of radioactive materials to the environment. Downwind air and ground concentrations and their associated doses from inhalation and ground shine pathways are estimated. The emergency response model (PUFF-PLUME) uses real-time data to track either instantaneous (puff) or continuous (plume) releases. A site-specific ingestion dose model was developed for use with PUFF-PLUME that includes the following ingestion dose pathways pertinent to the surrounding SRS area: milk, beef, water, and fish. The model is simplistic and can be used with existing code output

  1. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Richard P. [Univ. of California, Berkeley, CA (United States)

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  2. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    International Nuclear Information System (INIS)

    Levy, R.P.

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain

  3. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, R.P.

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  4. Dose projection for nuclear emergency response on a microcomputer

    International Nuclear Information System (INIS)

    Vold, E.; Mauro, J.; Michlewicz, D.

    1984-01-01

    A set of microcomputer programs were developed to implement the offsite steady-state dose projection calculations given in the Standard Operating Procedures for Nuclear Power Plant Emergency Response of the Radiologic Health Branch, California Department of Health Services. The dose projection system is intended for training, education and drill exercises for offsite nuclear emergency response staff. The simplicity of use and accuracy would be adequate for use as a back-up calculation to assist in determining emergency response in the event of an actual nuclear emergency. Nuclide release data and current meteorology is input by the user in response to program prompting. The output is specified from the options: (1) doses, dose rates and duration until the Protective Action Guides (PAGs) are exceeded at 2, 5 and 10 miles downwind; (2) dose and dose rates at any specified location; (3) isopleuths plotted on a site map; (4) user-specified isodoses plotted on a site map; (5) isodoses plotted equal to the PAGs. Six site maps to characterize the three current nuclear reactor sites in California can be displayed in full color for the plotting programs. Additional site maps can be added with an available low-cost digitizing tablet. Five separate dose pathways which cover the expected range in critical exposure pathways during a nuclear power plant accident can be calculated or plotted on a selected site map. Some dose projection results are presented, discussed and compared to other simple dose projection methods

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

    International Nuclear Information System (INIS)

    Elaguppillai, V.

    1981-01-01

    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)

  6. Mal-Development of the Penis and Loss of Fertility in Male Rats Treated Neonatally with Female Contraceptive 17α-Ethinyl Estradiol: A Dose-Response Study and a Comparative Study with a Known Estrogenic Teratogen Diethylstilbestrol

    Science.gov (United States)

    Mathews, Ensa; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Bolden-Tiller, Olga; Goyal, Hari O.

    2009-01-01

    The objectives of this study were to find a minimal dose of 17α-ethinyl estradiol (EE) that is detrimental to the developing penis and fertility and to compare estrogenic effects between EE and diethylstilbestrol (DES). Neonatal rats received EE at 10 ng (1 μg/kg), 100 ng, 1 μg, or 10 μg per pup on alternate days from postnatal days 1 to 11 (dose-response study) or received EE or DES at 100 ng per pup daily from postnatal days 1 to 6 (comparative study). Effects of EE were dose dependent, with ≥ 100-ng dose inducing significant (p penis was malformed, characterized by underdeveloped os penis and accumulation of fat cells. Fertility was 0% in the ≥ 1-μg groups, in contrast to 60% in the 100-ng group and 100% in the 10-ng and control groups. Animals treated with ≥ 10 ng had significant reductions in the weight of bulbospongious muscle, testis, seminal vesicle, epididymal fat pad, and in epididymal sperm numbers. A comparison of EE and DES effects showed similar reductions in penile weight and length and the weight of bulbospongiosus muscle, testis, seminal vesicle, epididymis, and epididymal fat pad in both adolescent and adult rats. While 5/6 control males sired, only 1/6 in the EE group and 0/6 in the DES group sired. Hence, neonatal exposure to EE at 10 ng (environmentally relevant dose) adversely affects male reproductive organs. A dose ten times higher than this leads to permanently mal-developed penis and infertility. Furthermore, EE and DES exposures show similar level of toxicity to male reproductive organs. PMID:19729556

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

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2015-01-01

    INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four or......, 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.......INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four oral......, whereas AEs often increase with increasing doses. The two other groups of drugs also have flat dose-response curves for efficacy. Overall, the triptans still have the most favorable efficacy-tolerability profile. Current acute antimigraine drugs do not fulfill the expectations of the patients, and thus...

  8. Linear reduction in thyroid cancer risk by oral contraceptive use: a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Wu, Lang; Zhu, Jingjing

    2015-09-01

    Is there an association between oral contraceptive (OC) use and thyroid cancer risk in females? OC use is inversely associated with the risk of thyroid cancer in females. OC use may be relevant to the risk of thyroid cancer as suggested by some epidemiological studies. However, the findings are inconsistent regarding the effect direction and size. This systematic review and meta-analysis included a total of 1906 patients from about 1.3 million individuals who had participated in 9 prospective cohort studies. The follow-up length ranged 7.5-15.9 years. PubMed (MEDLINE) was searched through to January 2015 for eligible studies. References of relevant review articles were also manually screened. Prospective cohort studies that evaluated the association between OC use and thyroid cancer risk were included. Study characteristics including patients' characteristics, length of the follow-up and risk estimates were extracted. The quality of the studies was also assessed. The included studies were of high methodological quality according to the Newcastle-Ottawa Quality Assessment Scale. After pooling risk estimates from all the studies, there was a significant inverse association between the longest versus shortest duration of OC use and the risk of thyroid cancer [relative risk (RR) = 0.84, 95% confidence interval (CI) 0.73-0.97], with no considerable heterogeneity (I(2) = 26.1%). There was no significant publication bias. The significant association persisted in the subgroup of high-quality studies (RR = 0.84, 95% CI 0.72-0.97). By dose-response analysis, there was a linear relationship (P = 0.0001) between the duration of OC use and thyroid cancer risk. The summary RR for an increment of 1 year of OC use was 0.96 (95% CI 0.94-0.98), with no significant heterogeneity. Individual patient data were unavailable for a more accurate estimation. These results indicate that OC use may decrease the risk of thyroid cancer in females. This may have implications for women

  9. Caffeine and sprinting performance: dose responses and efficacy.

    Science.gov (United States)

    Glaister, Mark; Patterson, Stephen D; Foley, Paul; Pedlar, Charles R; Pattison, John R; McInnes, Gillian

    2012-04-01

    The aims of this study were to evaluate the effects of caffeine supplementation on sprint cycling performance and to determine if there was a dose-response effect. Using a randomized, double-blind, placebo-controlled design, 17 well-trained men (age: 24 ± 6 years, height: 1.82 ± 0.06 m, and body mass(bm): 82.2 ± 6.9 kg) completed 7 maximal 10-second sprint trials on an electromagnetically braked cycle ergometer. Apart from trial 1 (familiarization), all the trials involved subjects ingesting a gelatine capsule containing either caffeine or placebo (maltodextrin) 1 hour before each sprint. To examine dose-response effects, caffeine doses of 2, 4, 6, 8, and 10 mg·kg bm(-1) were used. There were no significant (p ≥ 0.05) differences in baseline measures of plasma caffeine concentration before each trial (grand mean: 0.14 ± 0.28 μg·ml(-1)). There was, however, a significant supplement × time interaction (p caffeine doses producing higher postsupplementation plasma caffeine levels. In comparison with placebo, caffeine had no significant effect on peak power (p = 0.11), mean power (p = 0.55), or time to peak power (p = 0.17). There was also no significant effect of supplementation on pretrial blood lactate (p = 0.58), but there was a significant time effect (p = 0.001), with blood lactate reducing over the 50 minute postsupplementation rest period from 1.29 ± 0.36 to 1.06 ± 0.33 mmol·L(-1). The results of this study show that caffeine supplementation has no effect on short-duration sprint cycling performance, irrespective of the dosage used.

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Extremely low doses of X-radiation can induce adaptive responses in mouse prostate

    International Nuclear Information System (INIS)

    Day, T.K.; Zeng, G.; Hooker, A.M.; Turner, D.R.; Sykes, P.J.; Baht, M.

    2006-01-01

    Full text: The pKZl mouse chromosomal inversion assay is the only assay which has detected modulation of a mutagenic endpoint after single whole body X-irradiation with doses lower than 1 mGy. A non-linear dose response for chromosomal inversion has been observed between 1 jaGy and 10 mGy with doses between 5-10 uGy causing an induction in inversions and doses between 1-10 mGy causing a reduction below endogenous inversion frequency (Hooker et al, 2004. Radiat. Res. 162:447-52.) An adaptive response is a decreased biological effect induced by a priming radiation dose given prior to a challenge dose. Adaptive responses contradict the linear-no-threshold model of risk estimation. pKZl mice were exposed to priming radiation doses which by themselves either induced or reduced inversion frequency. Four hours later mice received a challenge dose of 1000 mGy. The inversion frequency was quantified in prostate three days later. We demonstrated that very low (10 mGy, 1 mGy and 10 )J,Gy) priming doses of X-radiation induced a chromosomal inversion adaptive response. These are the lowest X-radiation doses reported to induce an adaptive response for any endpoint. Reverse adaptive response experiments will also be discussed where the challenge dose studied was lower than the priming dose. Analysis of the distribution of inversions in 50 prostatic glands screened/animal suggested that there are two types of damage induced by the high challenge dose and only one of these types of damage is modified by the priming dose. Identification of the modifying factors involved in the adaptive response may provide candidates for radioprotection. This work was funded by the Low Dose Radiation Research Program, U.S. Department of Energy, grant no. DE-FG02-01ER63227 and DE-FG02-05ER64104

  12. 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

  13. The influence of dose fractionation and dose rate on normal tissue responses

    International Nuclear Information System (INIS)

    Barendsen, G.W.

    1982-01-01

    An analysis of responses of a variety of normal tissues in animals to fractionated irradiations has been made with the aim of developing a formalism for the prediction of tolerance doses as a function of the dose per fraction and the overall treatment time. An important feature of the formalism is that it is directly based on radiological insights and therefore provides a logical concept to account for the diversity of tissue responses. (Auth.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-03-15

    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.

  15. Long-term dose-response studies of inhaled or injected radionuclides. Biennial report, 1 October 1991--30 September 1993

    Energy Technology Data Exchange (ETDEWEB)

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L. [eds.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques.

  16. Laboratory measurement error in external dose estimates and its effects on dose-response analyses of Hanford worker mortality data

    International Nuclear Information System (INIS)

    Gilbert, E.S.; Fix, J.J.

    1996-08-01

    This report addresses laboratory measurement error in estimates of external doses obtained from personnel dosimeters, and investigates the effects of these errors on linear dose-response analyses of data from epidemiologic studies of nuclear workers. These errors have the distinguishing feature that they are independent across time and across workers. Although the calculations made for this report were based on Hanford data, the overall conclusions are likely to be relevant for other epidemiologic studies of workers exposed to external radiation

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  18. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  19. Updating Dosimetry for Emergency Response Dose Projections.

    Science.gov (United States)

    DeCair, Sara

    2016-02-01

    In 2013, the U.S. Environmental Protection Agency (EPA) proposed an update to the 1992 Protective Action Guides (PAG) Manual. The PAG Manual provides guidance to state and local officials planning for radiological emergencies. EPA requested public comment on the proposed revisions, while making them available for interim use by officials faced with an emergency situation. Developed with interagency partners, EPA's proposal incorporates newer dosimetric methods, identifies tools and guidelines developed since the current document was issued, and extends the scope of the PAGs to all significant radiological incidents, including radiological dispersal devices or improvised nuclear devices. In order to best serve the emergency management community, scientific policy direction had to be set on how to use International Commission on Radiological Protection Publication 60 age groups in dose assessment when implementing emergency guidelines. Certain guidelines that lend themselves to different PAGs for different subpopulations are the PAGs for potassium iodide (KI), food, and water. These guidelines provide age-specific recommendations because of the radiosensitivity of the thyroid and young children with respect to ingestion and inhalation doses in particular. Taking protective actions like using KI, avoiding certain foods or using alternative sources of drinking water can be relatively simple to implement by the parents of young children. Clear public messages can convey which age groups should take which action, unlike how an evacuation or relocation order should apply to entire households or neighborhoods. New in the PAG Manual is planning guidance for the late phase of an incident, after the situation is stabilized and efforts turn toward recovery. Because the late phase can take years to complete, decision makers are faced with managing public exposures in areas not fully remediated. The proposal includes quick-reference operational guidelines to inform re-entry to

  20. Radiation Dose-Response Relationships and Risk Assessment

    International Nuclear Information System (INIS)

    Strom, Daniel J.

    2005-01-01

    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

  1. Radiation Dose-Response Relationships and Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2005-07-05

    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

  2. I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident

    OpenAIRE

    Brenner, Alina V.; Tronko, Mykola D.; Hatch, Maureen; Bogdanova, Tetyana I.; Oliynik, Valery A.; Lubin, Jay H.; Zablotska, Lydia B.; Tereschenko, Valery P.; McConnell, Robert J.; Zamotaeva, Galina A.; O?Kane, Patrick; Bouville, Andre C.; Chaykovskaya, Ludmila V.; Greenebaum, Ellen; Paster, Ihor P.

    2011-01-01

    Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case?control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose?response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who ...

  3. The effect of ongoing exposure dynamics in dose response relationships.

    Directory of Open Access Journals (Sweden)

    Josep M Pujol

    2009-06-01

    Full Text Available Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, is a sequence of discrete events where concurrent or prior pathogen arrival affects the capacity of immune effectors to engage and kill newly arriving pathogens. We model immune effector and pathogen interactions during the period before infection becomes established in order to capture the dynamics generating dose timing effects. Model analysis reveals an inverse relationship between the time over which exposures accumulate and the risk of infection. Data from one time dose experiments will thus overestimate per pathogen infection risks of real world exposures. For instance, fitting our model to one time dosing data reveals a risk of 0.66 from 313 Cryptosporidium parvum pathogens. When the temporal exposure window is increased 100-fold using the same parameters fitted by our model to the one time dose data, the risk of infection is reduced to 0.09. Confirmation of this risk prediction requires data from experiments administering doses with different timings. Our model demonstrates that dose timing could markedly alter the risks generated by airborne versus fomite transmitted pathogens.

  4. The effects of in ovo mibolerone treatment on the bursa of Fabricius and the humoral system of chickens: a dose-response study.

    Science.gov (United States)

    Bhanushali, J K; Murthy, K K; Ragland, W L

    1985-10-01

    The effects of various doses of mibolerone, an analog of testosterone, in the development of the bursa of Fabricius and the humoral immune system were examined by injecting 0.01, 0.1, 1, 10 or 100 micrograms mibolerone into the chorio-allantoic cavity of 12-day-old chick embryos. Treatment with 0.01 or 0.1 micrograms of mibolerone caused slight or no bursal atrophy, 1 microgram caused substantial bursal atrophy, and 10 or 100 micrograms caused severe bursal atrophy at the time of hatching and at 6 weeks of age. When mibolerone-treated birds were challenged with sheep red blood cells and killed Brucella abortus at 4 and 5 weeks of age, birds treated with 10 or 100 micrograms of mibolerone had suppressed humoral responses to sheep erythrocytes and B. abortus whereas birds treated with 0.01 and 0.1 micrograms of mibolerone had normal humoral immune responses. Birds treated with 1 microgram mibolerone had normal humoral immune responses to sheep erythrocytes and B. abortus (except for low IgG responses to B. abortus) despite the fact that the birds had substantially atrophic bursae during their embryonic and post-embryonic development. These results are discussed in relation to an earlier claim that mibolerone given in microgram quantities in feed during the post-hatch period causes rapid development of the humoral immune system.

  5. Dose response of artificial irradiation of fluvial sediment sample for ESR dating

    International Nuclear Information System (INIS)

    Liu Chunru; Yin Gongming; Gao Lu; Li Jianping; Han Fei; Lin Min

    2011-01-01

    ESR dating samples need be irradiated to obtain dose response curve and the equivalent dose. The artificial dose rate is about 1 x 10 -1 -1 x 10 2 Gy/min, whereas the natural dose rate is about 3 Gy/ka. Therefore, one must be sure whether the much higher artificial dose rate is suitable for the ESR dating study. In this paper, we use different artificial dose rate to irradiate the same fluvial sample and measure the quartz Al centre ESR signal under the same conditions. The dose response curves are compared, in an attempt to gain a preliminary knowledge on that problem and build a good foundation for our ESR dating studies on fluvial samples. (authors)

  6. Immune Response And Anamnestic Immune Response In Children After A 3-Dose Primary Hepatitis B Vaccination.

    Science.gov (United States)

    Afzal, Muhammad Faheem; Sultan, Muhammad Ashraf; Saleemi, Ahmad Imran

    2016-01-01

    Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response & anamnestic immune response in children, 9 months-10 years of age, after a 3dose primary Hepatitis B vaccination. This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, documented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum antiHBsAb by ELIZA was measured. Children with antiHBs titers ≥10 mIU/mL were considered to be immune. Those with anti HBsAb levels immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Of the 200 children, protective antibody response was found in 58%. Median serological response was 18.60 (range 2.82 - 65.15). Antibody levels were found to have a statistically significant ( pvalue 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vacci ne was administered to all nonresponders, with each registering a statistically significant (pvalue 0.00) anamnestic response. The vaccination schedule with short dosage interval was unable to provide protection to 42% of the study population. Introduction of birth dose of Hepatitis B vaccine to the existing schedule is recommended.

  7. Biological effective dose studies in carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Yadav, Poonam; Ramasubramanian, V.

    2008-01-01

    Cancer of cervix is the second most common cancer worldwide among women. Several treatments related protocols of radiotherapy have been followed over few decades in its treatment for evaluating the response. These physical doses varying on the basics of fractionation size, dose rate and total dose needed to be indicated as biological effective dose (BED) to rationalize these treatments. The curative potential of radiation therapy in the management of carcinoma of the cervix is greatly enhanced by the use of intracavitary brachytherapy. Successful brachytherapy requires the high radiation dose to be delivered to the tumor where as minimum radiation dose reach to surrounding normal tissue. Present study is aimed to evaluate biologically effective dose in patients receiving high dose-rate brachytherapy plus external beam radiotherapy based on tumor cell proliferation values in cancer of the cervix patients. The study includes 30 patients' data as a retrospective analysis. In addition determine extent of a dose-response relationship existing between the biological effective dose at Point A and the bladder and rectum and the clinical outcomes

  8. 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...

  9. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale.

    Science.gov (United States)

    Strassman, R J; Qualls, C R; Uhlenhuth, E H; Kellner, R

    1994-02-01

    Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a double-blind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects

  10. Permanent induction of morphological abnormalities in the penis and penile skeletal muscles in adult rats treated neonatally with diethylstilbestrol or estradiol valerate: a dose-response study.

    Science.gov (United States)

    Goyal, Hari O; Braden, Tim D; Williams, Carol S; Dalvi, Prasad; Mansour, Mansour M; Williams, John W

    2005-01-01

    This study evaluated the effects of neonatal exposure to different doses of diethylstilbestrol (DES) or estradiol valerate (EV) on penile morphology, penile skeletal muscles, and fertility. Male pups received DES or EV at a dose of 10 microg, 1 microg, 100 ng, 10 ng, or 1 ng per rat on alternate days from postnatal days 2-12. Fertility was tested at 120 days, and tissues were examined at 150 days. Generally, DES and EV induced similar effects within the 10- and 1-microg groups. Fertility was reduced to 0; the weight, length, and diameter of the penis and the weight of penile skeletal muscles, especially bulbocavernosus muscle, were decreased (P penis were replaced by fat cells. Conversely, all of the above parameters were similar in controls and the lower dose groups, except in the 100-ng DES group, in which 4 of 7 males did not sire pups (compared with 1 of 7 in controls and 2 of 6 in the 100-ng EV group). The loss of fertility in these 4 males of the DES group and 1 male of the EV group was associated with partial release of the preputial sheath and abnormal penile morphology. Plasma testosterone was reduced (P testosterone.

  11. Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study.

    Science.gov (United States)

    Gopal, Srihari; Hough, David W; Xu, Haiyan; Lull, Julia M; Gassmann-Mayer, Cristiana; Remmerie, Bart M; Eerdekens, Marielle H; Brown, David W

    2010-09-01

    This 13-week, double-blind study evaluated the efficacy and safety of the atypical antipsychotic paliperidone palmitate (recently approved in the United States) versus placebo administered as monthly gluteal injections (after two initial doses given 1 week apart) in acutely symptomatic patients with schizophrenia. Patients (N=388) were randomly assigned (1 : 1 : 1 : 1) to paliperidone palmitate 50, 100, or 150 mg eq. or placebo. As the 150 mg eq. dose was administered to fewer patients (n=30) than planned, meaningful and definitive conclusions cannot be drawn from the results of this group. The change from baseline in Positive and Negative Syndrome Scale total score at endpoint showed improvement in both paliperidone palmitate 50 and 100 mg eq. groups but was significant only in the 100 mg eq. group (P=0.019). The paliperidone palmitate 50 (P=0.004) and 100 mg eq. (Por=2% of patients in any group) more frequent with paliperidone palmitate 50 or 100 mg eq. than placebo (>or=5% difference) were headache, vomiting, extremity pain, and injection site pain. Treatment with paliperidone palmitate (100 mg eq.) was efficacious and all doses tested were tolerable.

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

    International Nuclear Information System (INIS)

    Niemierko, Andrzej; Terahara, Atsuro; Goitein, Michael

    1997-01-01

    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

  13. Proposal of a probabilistic dose-response model

    International Nuclear Information System (INIS)

    Barrachina, M.

    1997-01-01

    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)

  14. Theory of thermoluminescence gamma dose response: The unified interaction model

    Science.gov (United States)

    Horowitz, Y. S.

    2001-09-01

    We describe the development of a comprehensive theory of thermoluminescence (TL) dose response, the unified interaction model (UNIM). The UNIM is based on both radiation absorption stage and recombination stage mechanisms and can describe dose response for heavy charged particles (in the framework of the extended track interaction model - ETIM) as well as for isotropically ionising gamma rays and electrons (in the framework of the TC/LC geminate recombination model) in a unified and self-consistent conceptual and mathematical formalism. A theory of optical absorption dose response is also incorporated in the UNIM to describe the radiation absorption stage. The UNIM is applied to the dose response supralinearity characteristics of LiF:Mg,Ti and is especially and uniquely successful in explaining the ionisation density dependence of the supralinearity of composite peak 5 in TLD-100. The UNIM is demonstrated to be capable of explaining either qualitatively or quantitatively all of the major features of TL dose response with many of the variable parameters of the model strongly constrained by ancilliary optical absorption and sensitisation measurements.

  15. Immune response and anamnestic immune response in children after a 3-dose primary hepatitis b vaccination

    International Nuclear Information System (INIS)

    Afzal, M.F.; Sultan, M.A.; Saleemi, A.I.

    2017-01-01

    Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response and anamnestic immune response in children, 9 months-10 years of age, after a 3-dose primary Hepatitis B vaccination. Methods: This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, docu mented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum anti-HBsAb by ELIZA was measured. Children with anti-HBs titers =10 mIU/mL were considered to be immune. Those with anti-HBsAb levels <10 mIU/mL were offered a booster dose of infant recombinant hepatitis B vaccine. The second serum sample was obtained 21-28 days following the administration of the booster dose and the anamnestic immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Results: Of the 200 children, protective antibody response was found in 58 percent. Median serological response was 18.60 (range 2.82-65.15). Antibody levels were found to have a statistically significant (p-value 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vaccine was administered to all non-responders, with each registering a statistically significant (p-value 0.00) anamnestic response. Conclusion: The vaccination schedule with short dosage interval was unable to provide

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

    Science.gov (United States)

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

    2016-10-01

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

  17. Evaluation of the dose-response relationship for intra-nasal oxymetazoline hydrochloride in normal adults.

    Science.gov (United States)

    Taverner, D; Bickford, L; Shakib, S; Tonkin, A

    1999-09-01

    To evaluate the dose-response relationship of increasing doses of oxymetazoline compared with placebo in normal subjects, and to determine the sensitivities of rhinomanometry, acoustic rhinometry and symptoms in discriminating between differing doses of oxymetazoline in normal subjects. The study had a randomized, double-blind, placebo-controlled, parallel group, dose-response design. One hundred and twenty-five healthy volunteers with no nasal obstruction were randomized to administration of a single intra-nasal dose of oxymetazoline (6.25 microg, 12.5 microg, 25 microg or 50 microg) or placebo to each nasal cavity. Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Total minimum cross-sectional area (tMCA) and volume (tVOL) were measured by acoustic rhinometry. Symptoms of congestion (CON) were assessed on a visual analogue scale. The two highest doses of oxymetazoline produced a significant decrease in NAR compared with placebo (P = 0.015) but not between placebo and 12.5 microg or 6.25 microg. There was a dose-response relationship for tVOL, which increased significantly after all doses compared with placebo (P oxymetazoline administered. tVOL provides a sensitive and discriminatory measure of small nasal changes after low doses of oxymetazoline. NAR is able to discriminate between doses, but is less sensitive than tVOL and tMCA, requiring a higher threshold dose before significant changes are seen in nasal patency.

  18. Maximum likelihood estimation for cytogenetic dose-response curves

    International Nuclear Information System (INIS)

    Frome, E.L.; DuFrain, R.J.

    1986-01-01

    In vitro dose-response curves are used to describe the relation between chromosome aberrations and radiation dose for human lymphocytes. The lymphocytes are exposed to low-LET radiation, and the resulting dicentric chromosome aberrations follow the Poisson distribution. The expected yield depends on both the magnitude and the temporal distribution of the dose. A general dose-response model that describes this relation has been presented by Kellerer and Rossi (1972, Current Topics on Radiation Research Quarterly 8, 85-158; 1978, Radiation Research 75, 471-488) using the theory of dual radiation action. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting dose-time-response models are intrinsically nonlinear in the parameters. A general-purpose maximum likelihood estimation procedure is described, and estimation for the nonlinear models is 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

  19. Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies.

    Science.gov (United States)

    Aune, Dagfinn; Keum, NaNa; Giovannucci, Edward; Fadnes, Lars T; Boffetta, Paolo; Greenwood, Darren C; Tonstad, Serena; Vatten, Lars J; Riboli, Elio; Norat, Teresa

    2016-06-14

     To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality.  PubMed and Embase searched up to 3 April 2016.  Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality.  Summary relative risks and 95% confidence intervals calculated with a random effects model.  45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings-for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I(2)=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I(2)=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I(2)=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I(2)=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I(2)=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I(2)=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I(2)=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I(2)=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I(2)=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I(2)=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular

  20. Hand-arm vibration syndrome and dose-response relation for vibration induced white finger among quarry drillers and stonecarvers. Italian Study Group on Physical Hazards in the Stone Industry.

    OpenAIRE

    Bovenzi, M

    1994-01-01

    OBJECTIVES--To investigate the occurrence of disorders associated with the hand arm vibration syndrome in a large population of stone workers in Italy. The dose-response relation for vibration induced white finger (VWF) was also studied. METHODS--The study population consisted of 570 quarry drillers and stonecarvers exposed to vibration and 258 control stone workers who performed only manual activity. Each subject was interviewed with health and workplace assessment questionnaires. Sensorineu...

  1. Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women

    DEFF Research Database (Denmark)

    Milman, Nils; Bergholt, Thomas; Eriksen, Lisbeth

    2005-01-01

    To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy.......To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy....

  2. Dose equivalent response of personal neutron dosemeters as a function of angle

    International Nuclear Information System (INIS)

    Tanner, J.E.; McDonald, J.C.; Stewart, R.D.; Wernli, C.

    1997-01-01

    The measured and calculated dose equivalent response as a function of angle has been examined for an albedo-type thermoluminescence dosemeter (TLD) that was exposed to unmoderated and D 2 O-moderated 252 Cf neutron sources while mounted on a 40 x 40 15 cm 3 polymethylmethacrylate phantom. The dosemeter used in this study is similar to many neutron personal dosemeters currently in use. The detailed construction of the dosemeter was modelled, and the dose equivalent response was calculated, using the MCNP code. Good agreement was found between the measured and calculated values of the relative dose equivalent angular response for the TLD albedo dosemeter. The relative dose equivalent angular response was also compared with the values of directional and personal dose equivalent as a function of angle published by Siebert and Schuhmacher. (author)

  3. Is there a dose response of dexamethasone as adjuvant for supraclavicular brachial plexus nerve block? A prospective randomized double-blinded clinical study.

    Science.gov (United States)

    Liu, Jiabin; Richman, Kenneth A; Grodofsky, Samuel R; Bhatt, Siya; Huffman, George Russell; Kelly, John D; Glaser, David L; Elkassabany, Nabil

    2015-05-01

    The study objective is to examine the analgesic effect of 3 doses of dexamethasone in combination with low concentration local anesthetics to determine the lowest effective dose of dexamethasone for use as an adjuvant in supraclavicular brachial plexus nerve block. The design is a prospective randomized double-blinded clinical study. The setting is an academic medical center. The patients are 89 adult patients scheduled for shoulder arthroscopy. All patients were randomly assigned into 1 of 4 treatment groups: (i) bupivacaine, 0.25% 30 mL; (ii) bupivacaine, 0.25% 30 mL with 1-mg preservative-free dexamethasone; (iii) bupivacaine, 0.25% 30 mL with 2-mg preservative-free dexamethasone; and (iv) bupivacaine, 0.25% 30 mL with 4-mg preservative-free dexamethasone. All patients received ultrasound-guided supraclavicular brachial plexus nerve blocks and general anesthesia. The measurements are the duration of analgesia and motor block. The median analgesia duration of supraclavicular brachial plexus nerve block with 0.25% bupivacaine was 12.1 hours; and 1-, 2-, or 4-mg dexamethasone significantly prolonged the analgesia duration to 22.3, 23.3, and 21.2 hours, respectively (P = .0105). Dexamethasone also significantly extended the duration of motor nerve block in a similar trend (P = .0247). Low-dose dexamethasone (1-2 mg) prolongs analgesia duration and motor blockade to the similar extent as 4-mg dexamethasone when added to 0.25% bupivacaine for supraclavicular brachial plexus nerve block. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Dose-response curve estimation: a semiparametric mixture approach.

    Science.gov (United States)

    Yuan, Ying; Yin, Guosheng

    2011-12-01

    In the estimation of a dose-response curve, parametric models are straightforward and efficient but subject to model misspecifications; nonparametric methods are robust but less efficient. As a compromise, we propose a semiparametric approach that combines the advantages of parametric and nonparametric curve estimates. In a mixture form, our estimator takes a weighted average of the parametric and nonparametric curve estimates, in which a higher weight is assigned to the estimate with a better model fit. When the parametric model assumption holds, the semiparametric curve estimate converges to the parametric estimate and thus achieves high efficiency; when the parametric model is misspecified, the semiparametric estimate converges to the nonparametric estimate and remains consistent. We also consider an adaptive weighting scheme to allow the weight to vary according to the local fit of the models. We conduct extensive simulation studies to investigate the performance of the proposed methods and illustrate them with two real examples. © 2011, The International Biometric Society.

  5. Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Song, You, E-mail: you.song@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås (Norway); Tollefsen, Knut Erik [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway)

    2014-11-15

    Highlights: • First study on early stress responses in salmon exposed to low-dose gamma radiation. • Dramatic dose-dependent transcriptional responses characterized. • Multiple modes of action proposed for gamma radiation. - Abstract: Due to the production of free radicals, gamma radiation may pose a hazard to living organisms. The high-dose radiation effects have been extensively studied, whereas the ecotoxicity data on low-dose gamma radiation is still limited. The present study was therefore performed using Atlantic salmon (Salmo salar) to characterize effects of low-dose (15, 70 and 280 mGy) gamma radiation after short-term (48 h) exposure. Global transcriptional changes were studied using a combination of high-density oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (qPCR). Differentially expressed genes (DEGs; in this article the phrase gene expression is taken as a synonym of gene transcription, although it is acknowledged that gene expression can also be regulated, e.g., at protein stability and translational level) were determined and linked to their biological meanings predicted using both Gene Ontology (GO) and mammalian ortholog-based functional analyses. The plasma glucose level was also measured as a general stress biomarker at the organism level. Results from the microarray analysis revealed a dose-dependent pattern of global transcriptional responses, with 222, 495 and 909 DEGs regulated by 15, 70 and 280 mGy gamma radiation, respectively. Among these DEGs, only 34 were commonly regulated by all radiation doses, whereas the majority of differences were dose-specific. No GO functions were identified at low or medium doses, but repression of DEGs associated with GO functions such as DNA replication, cell cycle regulation and response to reactive oxygen species (ROS) were observed after 280 mGy gamma exposure. Ortholog-based toxicity pathway analysis further showed that 15 mGy radiation

  6. Biophysical Monitoring and dose response characteristics of irradiated hemoglobin

    International Nuclear Information System (INIS)

    Elshemey, W.M; Selim, N.S.; Desouky, O.

    2003-01-01

    The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using LAXS and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were irradiated at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV- visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of two peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1 s t peak, recorded at 4.65 o , is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5 o , appeared to be related to its primary and secondary structure

  7. Maximum likelihood estimation for cytogenetic dose-response curves

    International Nuclear Information System (INIS)

    Frome, E.L; DuFrain, R.J.

    1983-10-01

    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)d 2 ], where t is the time and d is dose. The coefficient of the d 2 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 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.

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

    Science.gov (United States)

    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-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. PMID:26413900

  10. Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

    Science.gov (United States)

    Renouf, Mathieu; Marmet, Cynthia; Giuffrida, Francesca; Lepage, Mélissa; Barron, Denis; Beaumont, Maurice; Williamson, Gary; Dionisi, Fabiola

    2014-02-01

    Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    OpenAIRE

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

    2015-01-01

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

  12. Response of the EPI-200 human 3-D skin model to high and low doses of protons

    Data.gov (United States)

    National Aeronautics and Space Administration — Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different necessitating the direct study of low dose...

  13. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

    Science.gov (United States)

    Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

    2015-01-01

    In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

  14. Hand-arm vibration syndrome and dose-response relation for vibration induced white finger among quarry drillers and stonecarvers. Italian Study Group on Physical Hazards in the Stone Industry.

    Science.gov (United States)

    Bovenzi, M

    1994-09-01

    To investigate the occurrence of disorders associated with the hand arm vibration syndrome in a large population of stone workers in Italy. The dose-response relation for vibration induced white finger (VWF) was also studied. The study population consisted of 570 quarry drillers and stonecarvers exposed to vibration and 258 control stone workers who performed only manual activity. Each subject was interviewed with health and workplace assessment questionnaires. Sensorineural and VWF disorders were staged according to the Stockholm workshop scales. Vibration was measured on a representative sample of percussive and rotary tools. The 8 h energy equivalent frequency weighted acceleration (A (8)) and lifetime vibration doses were calculated for each of the exposed stone workers. Sensorineural and musculoskeletal symptoms occurred more frequently in the workers exposed to vibration than in the controls, but trend statistics did not show a linear exposure-response relation for these disorders. The prevalence of VWF was found to be 30.2% in the entire group exposed to vibration. Raynaud's phenomenon was discovered in 4.3% of the controls. VWF was strongly associated with exposure to vibration and a monotonic dose-response relation was found. According to the exposure data of this study, the expected percentage of stone workers affected with VWF tends to increase roughly in proportion to the square root of A(8) (for a particular exposure period) or in proportion to the square root of the duration of exposure (for a constant magnitude of vibration). Even although limited to a specific work situation, the dose-response relation for VWF estimated in this study suggests a time dependency such that halving the years of exposure allows a doubling of the energy equivalent vibration. According to these findings, the vibration exposure levels currently under discussion within the European Community seem to represent reasonable exposure limits for the protection of workers against

  15. Equivalent dose determination in foraminifera: analytical description of the CO{sub 2}{sup -}-signal dose-response curve

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, D. E-mail: dirk.hoffmann@iup.uni-heidelberg.de; Woda, C.; Mangini, A

    2003-02-01

    The dose-response of the CO{sub 2}{sup -}signal (g=2.0006) in foraminifera with ages between 19 and 300 ka is investigated. The sum of two exponential saturation functions is an adequate function to describe the dose-response curve up to an additional dose of 8000 Gy. It yields excellent dating results but requires an artificial doses of at least 5000 Gy. For small additional doses of about 500 Gy the single exponential saturation function can be used to calculate a reliable equivalent dose D{sub E}, although it does not describ the dose-response for higher doses. The CO{sub 2}{sup -}-signal dose-response indicates that the signal has two components of which one is less stable than the other.

  16. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses.

    Directory of Open Access Journals (Sweden)

    Hae Mi Joo

    Full Text Available Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6 and LAD2 cells, mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6 and LAD2 cells that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i. The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13, and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.

  17. Dose-response relation between physical activity and sick leave

    NARCIS (Netherlands)

    Proper, K.I.; Heuvel, S.G. van den; Vroome, E.M. de; Hildebrandt, V.H.; Beek, A.J. van der

    2006-01-01

    Objective: To investigate the dose-response relation between moderate and vigorous physical activity and sick leave in a working population. Methods: Data were used from three large Dutch databases: two continuous, cross sectional surveys among a representative sample of the Dutch population and one

  18. Intervention effect and dose-dependent response of Tanreqing ...

    African Journals Online (AJOL)

    We aim to assess the effect and dose-response relationships of Tanreqing injection on lipopolysacchaide (LPS) induced airway mucus hypersecretion in rats. Material and methods: Forty-eight male rats were randomly divided into four groups (12 per group). A rat model of airway mucus hypersecretion was generated with ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Kim, Yeon Ku; Song, Hi Sup [KAERI, Taejon (Korea, Republic of)

    1999-10-01

    This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronucleus showed a good dose-response relationship in the range of dose 0{approx}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.

  20. Response to low-dose herbicide selection in self-pollinated Avena fatua.

    Science.gov (United States)

    Busi, Roberto; Girotto, Marcelo; Powles, Stephen B

    2016-03-01

    When applied at the correct plant stage and dose, herbicides are highly toxic to plants. At reduced, low herbicide doses (below the recommended dose) plants can survive and display continuous and quantitative variation in dose-survival responses. Recurrent (directional) selection studies can reveal whether such a phenotypic variation in plant survival response to low herbicide dose is heritable and leads to herbicide resistance. In a common experimental garden study, we have subjected a susceptible population of self-pollinated hexaploid Avena fatua to low-dose recurrent selection with the ACCase-inhibiting herbicide diclofop-methyl for three consecutive generations. Significant differences in response to low-dose diclofop-methyl selection were observed between the selected progenies and parent plants, with a twofold diclofop-methyl resistance and cross-resistance to ALS-inhibiting herbicides. Thus, the capacity of self-pollinated A. fatua to respond to low-dose herbicide selection is marginal, and it is much lower than in cross-pollinated L. rigidum. Lolium rigidum in the same experiment evolved 40-fold diclofop-methyl resistance by progressive enrichment of quantitative resistance-endowing traits. Cross-pollination rate, genetic variation and ploidy levels are identified as possible drivers affecting the contrasting capacity of Avena versus Lolium plants to respond to herbicide selection and the subsequent likelihood of resistance evolution at low herbicide dose usage. © 2015 Society of Chemical Industry.

  1. Linear dose response curves in fungi and tradescantia

    International Nuclear Information System (INIS)

    Unrau, P.

    1999-07-01

    Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for 'pink' loss of

  2. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies.

    Science.gov (United States)

    Vally, H; Thompson, P J

    2001-10-01

    Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose sulfited wine challenge protocol was employed to establish if wine sensitive asthmatics as a group have an increased sensitivity to sulfites. In study 1, 24 asthmatic patients with a strong history of wine induced asthma were screened. Subjects showing positive responses to single blind high sulfite (300 ppm) wine challenge were rechallenged on separate days in a double blind, placebo controlled fashion with wines of varying sulfite levels to characterise their responses to these drinks. In study 2, wine sensitive asthmatic patients (n=12) and control asthmatics (n=6) were challenged cumulatively with wine containing increasing concentrations of sulfite in order to characterise further their sensitivity to sulfites in wine. Four of the 24 self-reporting wine sensitive asthmatic patients were found to respond to sulfite additives in wine when challenged in a single dose fashion (study 1). In the double blind dose-response study all four had a significant fall in forced expiratory volume in one second (FEV(1)) (>15% from baseline) following exposure to wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Responses were maximal at 5 minutes (mean (SD) maximal decline in FEV(1) 28.7 (13)%) and took 15-60 minutes to return to baseline levels. In the cumulative dose-response study (study 2) no significant difference was observed in any of the lung function parameters measured (FEV(1), peak expiratory flow (PEF), mid phase forced expiratory flow (FEF(25-75))) between wine

  3. Response of MOSFETs from DMILL technology to high total doses

    International Nuclear Information System (INIS)

    Armani, J.M.; Brisset, C.; Joffre, F.; Dentan, M.

    1999-01-01

    We have studied the behaviour of MOS transistors with DMILL technology submitted to 60 Co gamma radiation. The cumulated dose was 1 MGy(Si) with a dose rate of 1 kGy(Si). The shift of the threshold voltage for an integrated dose beyond 1 MGy(Si) was less than 0.87 V even in the worst case. The analysis of the results shows that the effects of the traps located at the interface Si-SiO 2 become predominant for doses just over a few hundreds kilo-Gray. The weak shift observed enables DMILL-MOS transistors to be validated in civil nuclear applications where cumulated doses may be high. (A.C.)

  4. Parameterizing Dose-Response Models to Estimate Relative Potency Functions Directly

    Science.gov (United States)

    Dinse, Gregg E.

    2012-01-01

    Many comparative analyses of toxicity assume that the potency of a test chemical relative to a reference chemical is constant, but employing such a restrictive assumption uncritically may generate misleading conclusions. Recent efforts to characterize non-constant relative potency rely on relative potency functions and estimate them secondarily after fitting dose-response models for the test and reference chemicals. We study an alternative approach of specifying a relative potency model a priori and estimating it directly using the dose-response data from both chemicals. We consider a power function in dose as a relative potency model and find that it keeps the two chemicals’ dose-response functions within the same family of models for families typically used in toxicology. When differences in the response limits for the test and reference chemicals are attributable to the chemicals themselves, the older two-stage approach is the more convenient. When differences in response limits are attributable to other features of the experimental protocol or when response limits do not differ, the direct approach is straightforward to apply with nonlinear regression methods and simplifies calculation of simultaneous confidence bands. We illustrate the proposed approach using Hill models with dose-response data from U.S. National Toxicology Program bioassays. Though not universally applicable, this method of estimating relative potency functions directly can be profitably applied to a broad family of dose-response models commonly used in toxicology. PMID:22700543

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

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  6. Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a french population-based case-control study; Mesotheliome pleural: relation dose-reponse a faibles niveaux d'exposition a l'amiante dans une etude cas-temoins au sein d'une polulation francaise

    Energy Technology Data Exchange (ETDEWEB)

    Iwatsubo, Y.; Pairo, J.C.; Boutin, C.; Menard, O.; Massin, N.; Caillaud, D.; Orlowski, E.; Galateau-Salle, F.; Bignon, J.; Brochard, P.

    1998-03-01

    The objectives of this study were to study the dose-response relationship between professional exposure to asbestos and the supervening of the pleural mesothelioma in general population. This work notes an excess of death by pulmonary cancer among the asbestos-cement workers but one can regret the weakness of the exposure estimation (only one source of exposure is considered) and that some others risk factors have not been taken into account (tobacco, for example). (N.C.)

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

    International Nuclear Information System (INIS)

    Myers, D.K.

    1980-01-01

    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)

  8. Kinetics of the early adaptive response and adaptation threshold dose

    International Nuclear Information System (INIS)

    Mendiola C, M.T.; Morales R, P.

    2003-01-01

    The expression kinetics of the adaptive response (RA) in mouse leukocytes in vivo and the minimum dose of gamma radiation that induces it was determined. The mice were exposed 0.005 or 0.02 Gy of 137 Cs like adaptation and 1h later to the challenge dose (1.0 Gy), another group was only exposed at 1.0 Gy and the damage is evaluated in the DNA with the rehearsal it makes. The treatment with 0. 005 Gy didn't induce RA and 0. 02 Gy causes a similar effect to the one obtained with 0.01 Gy. The RA was show from an interval of 0.5 h being obtained the maximum expression with 5.0 h. The threshold dose to induce the RA is 0.01 Gy and in 5.0 h the biggest quantity in molecules is presented presumably that are related with the protection of the DNA. (Author)

  9. Biochemical and immunological responses to low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Shabon, M.H.; Sayed, Z.S.; Mahdy, E.M.; El-Gawish, M.A.; Shosha, W.

    2006-01-01

    Malondialdehyde, lactate dehydrogenase, iron concentration, IL-6 and IL-1b concentration, hemoglobin content, red cells, white cells and platelet counts were determined in seventy-two male albino rats divided into two main groups. The first one was subdivided into 7 subgroups; control and 6 irradiated subgroups with 0.1, 0.2, 0.3, 0.5, 0.7 and 1 Gy single dose of gamma radiation. The other was subdivided into 4 subgroups irradiated with fractionated doses of gamma radiation; three groups were irradiated with 0.3, 0.7 and 1 Gy (0.1 Gy/day) and the last subgroup with 1 Gy (0.2 Gy/day). All animals were sacrificed after three days of the last irradiation dose. The results revealed that all biochemical parameters were increased in rats exposed to fractionated doses more than the single doses. Hematological parameters were decreased in rats exposed to single doses more than the fractionated ones. In conclusion, the data of this study highlights the stimulatory effect of low ionizing radiation doses (= 1 Gy), whether single or fractionated, on some biochemical and immunological parameters

  10. [Anti-HBs persistence following revaccination with three doses of hepatitis B vaccine among low-responsive adults after primary vaccination: a 4-year follow-up study].

    Science.gov (United States)

    Lyu, J J; Yin, X W; Yan, B Y; Liu, J Y; Feng, Y; Wu, W L; Chen, S Y; Zhou, L B; Liang, X F; Cui, F Q; Wang, F Z; Zhang, L; Xu, A Q

    2016-06-01

    To assess the 4-year anti-HBs persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responsive adults. A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The 892 low-responders were revaccinated with three doses of HepB at 0-1-6 months schedule and the type of HepB was the same as which was used for primary immunization. During the follow-up to low-responders, the following informations were collected: the demographic characteristics (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and four years after revaccination and anti-HBs, anti-HBc and HBsAg (if anti-HBs low-responders. Among 529 participants, 276 (52.2%) were males and 253 (47.8%) were females. The positive rate was 82.6% (437/529) at T1 and it decreased to 28.2% (149/529) four years after revaccination. The corresponding GMC decreased from 542.06 (95% CI

  11. Dose-response and concentration-response relation of rocuronium infusion during propofol nitrous oxide and isoflurane nitrous oxide anaesthesia

    NARCIS (Netherlands)

    Kansanaho, M; Olkkola, KT; Wierda, JMKH

    The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during proporfol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback

  12. Dose-Response of Sodium Bicarbonate Ingestion Highlights Individuality in Time Course of Blood Analyte Responses.

    Science.gov (United States)

    Jones, Rebecca Louise; Stellingwerff, Trent; Artioli, Guilherme Giannini; Saunders, Bryan; Cooper, Simon; Sale, Craig

    2016-10-01

    To defend against hydrogen cation accumulation and muscle fatigue during exercise, sodium bicarbonate (NaHCO 3 ) ingestion is commonplace. The individualized dose-response relationship between NaHCO 3 ingestion and blood biochemistry is unclear. The present study investigated the bicarbonate, pH, base excess and sodium responses to NaHCO 3 ingestion. Sixteen healthy males (23 ± 2 years; 78.6 ± 15.1 kg) attended three randomized order-balanced, nonblinded sessions, ingesting a single dose of either 0.1, 0.2 or 0.3 g·kg -1 BM of NaHCO 3 (Intralabs, UK). Fingertip capillary blood was obtained at baseline and every 10 min for 1 hr, then every 15 min for a further 2 hr. There was a significant main effect of both time and condition for all assessed blood analytes (p ≤ .001). Blood analyte responses were significantly lower following 0.1 g·kg -1 BM compared with 0.2 g·kg -1 BM; bicarbonate concentrations and base excess were highest following ingestion of 0.3 g·kg -1 BM (p ≤ .01). Bicarbonate concentrations and pH significantly increased from baseline following all doses; the higher the dose the greater the increase. Large interindividual variability was shown in the magnitude of the increase in bicarbonate concentrations following each dose (+2.0-5; +5.1-8.1; and +6.0-12.3 mmol·L -1 for 0.1, 0.2 and 0.3 g·kg -1 BM) and in the range of time to peak concentrations (30-150; 40-165; and 75-180 min for 0.1, 0.2 and 0.3 g·kg -1 BM). The variability in bicarbonate responses was not affected by normalization to body mass. These results challenge current practices relating to NaHCO 3 supplementation and clearly show the need for athletes to individualize their ingestion protocol and trial varying dosages before competition.

  13. Airway responsiveness to hypertonic saline : dose-response slope or PD15?

    NARCIS (Netherlands)

    de Meer, G; Marks, GB; de Jongste, JC; Brunekreef, B

    The result of airway challenge test with hypertonic saline (HS) is expressed as the dose causing a 15% fall in forced expiratory volume in one second (FEV1; PD15). A noncensored measure, such as the dose-response slope (DRS), allows the evaluation of the risk of asthma for subjects with a fall in

  14. The association and dose-response relationship between dietary intake of α-linolenic acid and risk of CHD: a systematic review and meta-analysis of cohort studies.

    Science.gov (United States)

    Wei, Jingkai; Hou, Ruixue; Xi, Yuzhi; Kowalski, Alysse; Wang, Tiansheng; Yu, Zhi; Hu, Yirui; Chandrasekar, Eeshwar K; Sun, Hao; Ali, Mohammed K

    2018-01-01

    Previous studies show inconsistent associations between α-linolenic acid (ALA) and risk of CHD. We aimed to examine an aggregate association between ALA intake and risk of CHD, and assess for any dose-response relationship. We searched the PubMed, EMBASE and Web of Science databases for prospective cohort studies examining associations between ALA intake and CHD, including composite CHD and fatal CHD. Data were pooled using random-effects meta-analysis models, comparing the highest category of ALA intake with the lowest across studies. Subgroup analysis was conducted based on study design, geographic region, age and sex. For dose-response analyses, we used two-stage random-effects dose-response models. In all, fourteen studies of thirteen cohorts were identified and included in the meta-analysis. The pooled results showed that higher ALA intake was associated with modest reduced risk of composite CHD (risk ratios (RR)=0·91; 95 % CI 0·85, 0·97) and fatal CHD (RR=0·85; 95 % CI 0·75, 0·96). The analysis showed a J-shaped relationship between ALA intake and relative risk of composite CHD (χ 2=21·95, P<0·001). Compared with people without ALA intake, only people with ALA intake <1·4 g/d showed reduced risk of composite CHD. ALA intake was linearly associated with fatal CHD - every 1 g/d increase in ALA intake was associated with a 12 % decrease in fatal CHD risk (95 % CI -0·21, -0·04). Though a higher dietary ALA intake was associated with reduced risk of composite and fatal CHD, the excess composite CHD risk at higher ALA intakes warrants further investigation, especially through randomised controlled trials.

  15. Cytogenetics dosimetry: dose-response curve for low doses of X-ray; Dosimetria citogenetica: curva dosis-respuesta para bajas dosis de rayos-X

    Energy Technology Data Exchange (ETDEWEB)

    Lara, Virginia E. Noval; Pineda Bolivar, William R.; Riano, Victor M. Pabon, E-mail: venovall.15@hotmail.com, E-mail: wrpineda@misena.edu.co, E-mail: vmpabonr@udistrital.edu.co [Universidad Distrital Francisco Jose de Caldas (UD), Bogota (Colombia). Grupo de Investigacion en Ciencia y Tecnologia Nuclear; Ureana, Cecilia Crane, E-mail: cecicrane@yahoo.com [Instituto Nacional de Salud (INS), Bogota (Colombia). Laboratorio de Genetica

    2013-07-01

    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.

  16. A simple amino acid dose-response technique to quantify amino acid requirements of individual meal-fed pigs

    NARCIS (Netherlands)

    Kampman-van de Hoek, E.; Gerrits, W.J.J.; Peet-Schwering, van der C.M.C.; Jansman, A.J.M.; Borne, van den J.J.G.C.

    2013-01-01

    Two experiments were conducted to develop a simplified dose-response technique to estimate the Lys requirement of individual, meal-fed growing pigs. In Exp. 1, we studied adaptation processes that occur during such a dose-response study in meal-fed pigs, and in Exp. 2, we studied the accuracy of

  17. CBF and CMRo/sub 2/ during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, J.B.; Cold, G.E.; Eriksen, H.O.; Eskesen, V.; Blatt-Lyon, B.

    1986-01-01

    In 14 patients with supratentorial cerebral tumors with midline shift less than or equal to 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo/sub 2/) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety and Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In group 1 (n=7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRo/sub 2/ measured about 70 min after induction averaged 30.1 ml 100 g/sup -1/ min/sub -1/ and 1.98 ml O/sub 2/ 100 g/sup -1/ min/sup -1/, respectively. During the second CBF study 1 h later, CBF and CMRo/sub 2/ were unchanged (P>0.05). In group 2 (n=7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRo/sub 2/ was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRo/sub 2/ and suppression in the EEG activity, whereas CBF was unchanged.

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  19. Identifying the most successful dose (MSD) in dose-finding studies in cancer.

    Science.gov (United States)

    Zohar, Sarah; O'Quigley, John

    2006-01-01

    For a dose finding study in cancer, the most successful dose (MSD), among a group of available doses, is that dose at which the overall success rate is the highest. This rate is the product of the rate of seeing non-toxicities together with the rate of tumor response. A successful dose finding trial in this context is one where we manage to identify the MSD in an efficient manner. In practice we may also need to consider algorithms for identifying the MSD which can incorporate certain restrictions, the most common restriction maintaining the estimated toxicity rate alone below some maximum rate. In this case the MSD may correspond to a different level than that for the unconstrained MSD and, in providing a final recommendation, it is important to underline that it is subject to the given constraint. We work with the approach described in O'Quigley et al. [Biometrics 2001; 57(4):1018-1029]. The focus of that work was dose finding in HIV where both information on toxicity and efficacy were almost immediately available. Recent cancer studies are beginning to fall under this same heading where, as before, toxicity can be quickly evaluated and, in addition, we can rely on biological markers or other measures of tumor response. Mindful of the particular context of cancer, our purpose here is to consider the methodology developed by O'Quigley et al. and its practical implementation. We also carry out a study on the doubly under-parameterized model, developed by O'Quigley et al. but not

  20. Dose-Response Effects of Long-Acting Liquid Methylphenidate in Children with Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD): A Pilot Study

    Science.gov (United States)

    Kim, Soo-Jeong; Shonka, Sophia; French, William P.; Strickland, Jennifer; Miller, Lindsey; Stein, Mark A.

    2017-01-01

    Attention deficit/hyperactivity disorder (ADHD) symptoms are common in youth with autism spectrum disorders (ASD) and are frequently treated with stimulant medications. Twenty-seven children were randomized to different dose titration schedules, and ADHD symptoms, tolerability, and aberrant behaviors were assessed weekly during a 6-week trial with…

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

    Science.gov (United States)

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

    2009-02-01

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

  2. 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

    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....

  3. In vitro study of dose-response relationship of fluoride with dental enamel = Estudo in vitro da relação dose-resposta do fluoreto com esmalte dental

    Directory of Open Access Journals (Sweden)

    Arthur, Rodrigo Alex

    2007-01-01

    Full Text Available Modelos in vitro para avaliação da reatividade do fluoreto (F devem apresentar resposta dose-efeito. Dessa forma, o objetivo desse estudo foi avaliar a relação dose-resposta do fluoreto presente em solução aquosa com o esmalte dental bovino. Cento e vinte blocos de esmalte bovino (5 × 5 × 2 mm, 60 hígidos e 60 com lesão artificial de cárie, foram submetidos durante 10 minutos à água destilada e deionizada (controle negativo e soluções aquosas contendo 50, 100, 200 ou 400 µg F/mL. Cada grupo experimental recebeu 12 blocos hígidos e 12 blocos com lesão artificial de cárie. Duas camadas consecutivas de esmalte dental foram removidas de todos os blocos dentais por meio de ataque ácido e o fluoreto extraído foi determinado com eletrodo específico. Os resultados de fluoreto incorporado foram expressos em µg por g de esmalte removido, considerando a quantidade total das duas camadas. A incorporação de fluoreto pelo esmalte hígido mostrou uma relação dose-resposta linear (p = 0,0001, enquanto que os blocos com lesão de cárie mostraram relação polinomial quadrática (p < 0,0001. Os resultados sugerem que o modelo in vitro de reatividade empregado no presente estudo é apropriado para avaliar a relação doseresposta entre o fluoreto em solução aquosa e aquele incorporado pelo esmalte dental bovino hígido ou com lesão artificial de cárie

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

    International Nuclear Information System (INIS)

    Calabrese, Edward J.; Bachmann, Kenneth A.; Bailer, A. John; Bolger, P. Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M. George; Chiueh, Chuang C.; Clarkson, Thomas W.; Cook, Ralph R.; Diamond, David M.; Doolittle, David J.; Dorato, Michael A.; Duke, Stephen O.; Feinendegen, Ludwig; Gardner, Donald E.; Hart, Ronald W.; Hastings, Kenneth L.; Hayes, A. Wallace; Hoffmann, George R.; Ives, John A.; Jaworowski, Zbigniew; Johnson, Thomas E.; Jonas, Wayne B.; Kaminski, Norbert E.; Keller, John G.; Klaunig, James E.; Knudsen, Thomas B.; Kozumbo, Walter J.; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I.; Masoro, Edward J.; McClellan, Roger O.; Mehendale, Harihara M.; Mothersill, Carmel; Newlin, David B.; Nigg, Herbert N.; Oehme, Frederick W.; Phalen, Robert F.; Philbert, Martin A.; Rattan, Suresh I.S.; Riviere, Jim E.; Rodricks, Joseph; Sapolsky, Robert M.; Scott, Bobby R.; Seymour, Colin; Sinclair, David A.; Smith-Sonneborn, Joan; Snow, Elizabeth T.; Spear, Linda; Stevenson, Donald E.; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M.; Mattson, Mark P.

    2007-01-01

    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

  5. Time and total dose response of non-volatile UVPROMs

    International Nuclear Information System (INIS)

    Sampson, D.F.

    1988-01-01

    While survivability testing of floating gate non-volatile UVPROM memory devices has been documented in numerous journals, this paper reports on the total dose radiation response and intrinsic charge loss as a function of operating time in a system. Five groups of Intel and Signetics 27C256 devices were aged from one to five years through accelerated bake to simulate system use. Characterizations of the groups with five years of simulated use will be presented in detail in this paper. Device margin voltage was characterized before and after aging and after exposure to five total dose radiation levels (1K - 5K rads (Si)). A statistical model based upon the characterization data was developed to establish re-programming intervals for these devices when used in airborne electronic systems

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

    International Nuclear Information System (INIS)

    Metz-Flamant, Camille

    2011-01-01

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

  7. AS03-adjuvanted, very-low-dose influenza vaccines induce distinctive immune responses compared to unadjuvanted high-dose vaccines in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Karen K Yam

    2015-04-01

    Full Text Available During the 2009-2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed three weeks after the booster. Unadjuvanted ‘high’ (3µg and low dose (0.03µg-0.003µg vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted ‘high-dose’ vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of ‘standard’ doses of vaccines in pre-clinical vaccine studies.

  8. Temporal analysis of a dose-response relationship: leukemia mortality in atomic bomb survivors.

    Science.gov (United States)

    Brodsky, J B; Groer, P G; Liddell, R; Ishimaru, T; Ichimaru, M

    1984-09-01

    A data analysis that incorporates time dependencies is demonstrated for the dose response of leukemia mortality in the atomic bomb survivors. The time dependencies are initially left unspecified and the data on leukemia mortality--up to the end of 1978--are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-dependent L (linear in gamma dose)-Q (quadratic in gamma dose)-L (linear in neutron dose), L-L, and Q-L dose-response models are significantly improved (P less than 0.001) by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to gamma irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time (P = 0.002) and the current definition of RBE as a time-independent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit (P = 0.01) to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period (P greater than 0.30).

  9. Emergency response system upgrade with a dose assessment block

    International Nuclear Information System (INIS)

    Syrakov, D.; Veleva, B.; Prodanova, M.; Popova, T.; Kolarova, M.

    2006-01-01

    The need of fast and reliable estimation of the possible impacts of hazardous substances transferred from long range air pollution over the Bulgarian territory requires development and implementation of an adequate diagnostic and prognostic modeling systems - so called Emergency Response System (ERS) based on real and forecast meteorological information and numerical models accounting for the transport, dispersion, chemical and radioactive transformations of pollutants as well as removal processes. In Bulgarian NIMH, an Early Warning System for transport of radioactive pollutants was developed by D.Syrakov and M.Prodanova in mid 90's of the last century, tested during the ETEX experiments and a number of international and national exercises, like INEX-1 (1995), INEX-2-CH-'Fortuna' (1996), INEX-2-FIN (1997), JINEX 1 (2001), AXIOPOLIS'2001, CONVEX-3 (2005). The system was adopted also for operational calculations and visualization of trajectories over Europe and the North hemisphere originating from part of the most potential sources of accidental radioactive releases - the Nuclear Power Plants. For realistic evaluation of the pollution levels and human health effects in case of nuclear accident, this EWS was upgraded further in several main directions: 1) a mixture of radioactive pollutants is considered instead of one pollutant arbitrary called radioactivity with parameters of a weightless gas; 2) the different radionuclides are grouped based on their dispersion properties; 3) new source term is created being able to account for the evolution of the release; 4) a small data base of possible release scenarios is a supplement to the source term; 5) the EMAP model is upgraded with a 'dose calculation block' where the output of the dispersion model is transformed into fields of doses thus presenting the information in a form much more appropriate for decision making. The effective dose from external irradiation from cloud and ground shinning, effective dose from

  10. Adaptive response of human lymphocytes to low dose radiation on DNA synthesis

    International Nuclear Information System (INIS)

    Du Zeji; Su Liaoyuan; Tian Hailin

    1995-01-01

    Human peripheral blood lymphocytes PHA-stimulated in vitro for 24 h were exposed to low dose γ-ray irradiation (adaptive dose), they showed an adaptive response to the inhibition of DNA synthesis by subsequent higher acute doses of γ-ray (challenge dose). At the interval of 24 h between adaptive dose and challenge dose, the most obvious adaptive response induced by low dose irradiation was found. It was also found that the response induced by 1.0 cGy of adaptive dose was more obvious than that by other doses. In the challenge doses range of 1.0∼7.0 Gy, the adaptive response was observed and that 3.0 Gy was more obvious. The adaptive response disappeared with the challenge doses further increased

  11. Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats.

    Science.gov (United States)

    Hichri, Oubeidallah; Laurin, Jean-C; Julien, Cécile A; Joseph, Vincent; Bairam, Aida

    2012-01-01

    The effect of progesterone as a respiratory stimulant in newborn subjects is less known than that in adults. This study investigated the dose-response curve (0, 2, 4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn rats at 4- and 12-days old using plethysmography. Progesterone had no effects in the regulation of normoxic ventilation. However, it enhanced the response to moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This response was similar between the dose of 4 and 8 mg/kg. These observations suggested that progesterone enhances in age- and dose-dependent manner the hypoxic ventilatory response in newborn rats.

  12. 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.

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

    International Nuclear Information System (INIS)

    Yuece, Ulkue Rabia; Meric, Niyazi; Atakol, Orhan; Yasar, Fusun

    2010-01-01

    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.

  14. Response of radiation monitors for ambient dose equivalent, H*(10)

    International Nuclear Information System (INIS)

    Grecco, Claudio Henrique dos Santos

    2001-01-01

    Radiation monitors are used all over the world to evaluate if places with presence of ionising radiation present safe conditions for people. Radiation monitors should be tested according to international or national standards in order to be qualified for use. This work describes a methodology and procedures to evaluate the energy and angular responses of any radiation monitor for ambient dose equivalent, H*(10), according to the recommendations of ISO and IEC standards. The methodology and the procedures were applied to the Monitor Inteligente de Radiacao MIR 7026, developed by the Instituto em Engenharia Nuclear (IEN), to evaluate and to adjust its response for H*(10), characterizing it as an ambient dose equivalent meter. The tests were performed at the Laboratorio Nacional de Metrologia das Radiacoes Ionizantes (LNMRI), at Instituto de Radioprotecao e Dosimetria (IRD), and results showed that the Monitor Inteligente de Radiacao MIR 7026 can be used as an EI*(10) meter, in accordance to the IEC 60846 standard requirements. The overall estimated uncertainty for the determination of the MIR 7026 response, in all radiation qualities used in this work, was 4,5 % to a 95 % confidence limit. (author)

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

    International Nuclear Information System (INIS)

    Raabe, O.G.

    1988-01-01

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

  16. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    Directory of Open Access Journals (Sweden)

    Rui-Ru Ji

    2009-09-01

    Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

  17. Anti-irritants I: Dose-response in acute irritation

    DEFF Research Database (Denmark)

    Andersen, Flemming; Hedegaard, Kathryn; Petersen, Thomas Kongstad

    2006-01-01

    acute irritation in healthy volunteers. Each AI was used in 3 concentrations. Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate and 20% nonanoic acid in N-propanol. The irritant reactions were treated twice daily with AI-containing formulations from the time of removal...... of the patches. Evaluation of skin irritation and efficacy of treatments were performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colourimetry. Only glycerol showed dose-response and effects potentially better than no treatment...

  18. Anti-irritants I: Dose-response in acute irritation

    DEFF Research Database (Denmark)

    Andersen, Flemming; Hedegaard, Kathryn; Petersen, Thomas Kongstad

    2006-01-01

    The term 'anti-irritant' (AI) was coined in 1965 by Goldemberg to describe a diverse group of topical product ingredients, which were able to reduce the irritation potential of other more irritating ingredients in the same product. 'AIs' are being added to cosmetic formulations in order, allegedly...... of the patches. Evaluation of skin irritation and efficacy of treatments were performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colourimetry. Only glycerol showed dose-response and effects potentially better than no treatment...

  19. Radiation dose response estimation with emphasis on low dose range using restricted cubic splines: application to all solid cancer mortality data, 1950-2003, in atomic bomb survivors.

    Science.gov (United States)

    Nakashima, Eiji

    2015-07-01

    Using the all solid cancer mortality data set of the Life Span Study (LSS) cohort from 1950 to 2003 (LSS Report 14) data among atomic bomb survivors, excess relative risk (ERR) statistical analyses were performed using the second degree polynomial and the threshold and restricted cubic spline (RCS) dose response models. For the RCS models with 3 to 7 knots of equally spaced percentiles with margins in the dose range greater than 50 mGy, the dose response was assumed to be linear at less than 70 to 90 mGy. Due to the skewed dose distribution of atomic bomb survivors, the current knot system for the RCS analysis results in a detailed depiction of the dose response as less than approximately 0.5 Gy. The 6 knot RCS models for the all-solid cancer mortality dose response of the whole dose or less than 2 Gy were selected with the AIC model selection criterion and fit significantly better (p cubic spline in the lower and upper tails, and the best RCS model selected with AIC criterion was the usual RCS with L-constraints in both the lower and upper tails. The selected RCS had a linear dose-response model in the lower dose range (i.e., < 0.2-0.3 Gy) and was compatible with the linear no-threshold (LNT) model in this dose range. The proposed method is also useful in describing the dose response of a specific cancer or non-cancer disease incidence/mortality.

  20. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  1. TU-D-201-07: Severity Indication in High Dose Rate Brachytherapy Emergency Response Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Li, K [Associates in Medical Physics, Hagerstown, MD (United States); Rustad, F [Associates In Medical Physics, Lanham, MD (United States)

    2016-06-15

    Purpose: Understanding the corresponding dose to different staff during the High Dose Rate (HDR) Brachytherapy emergency response procedure could help to develop a strategy in efficiency and effective action. In this study, the variation and risk analysis methodology was developed to simulation the HDR emergency response procedure based on severity indicator. Methods: A GammaMedplus iX HDR unit from Varian Medical System was used for this simulation. The emergency response procedure was decomposed based on risk management methods. Severity indexes were used to identify the impact of a risk occurrence on the step including dose to patient and dose to operation staff by varying the time, HDR source activity, distance from the source to patient and staff and the actions. These actions in 7 steps were to press the interrupt button, press emergency shutoff switch, press emergency button on the afterloader keypad, turn emergency hand-crank, remove applicator from the patient, disconnect transfer tube and move afterloader from the patient, and execute emergency surgical recovery. Results: Given the accumulated time in second at the assumed 7 steps were 15, 5, 30, 15, 180, 120, 1800, and the dose rate of HDR source is 10 Ci, the accumulated dose in cGy to patient at 1cm distance were 188, 250, 625, 813, 3063, 4563 and 27063, and the accumulated exposure in rem to operator at outside the vault, 1m and 10cm distance were 0.0, 0.0, 0.1, 0.1, 22.6, 37.6 and 262.6. The variation was determined by the operators in action at different time and distance from the HDR source. Conclusion: The time and dose were estimated for a HDR unit emergency response procedure. It provided information in making optimal decision during the emergency procedure. Further investigation would be to optimize and standardize the responses for other emergency procedure by time-spatial-dose severity function.

  2. 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%.

  3. Cranberry (poly)phenol metabolites correlate with improvements in vascular function: A double-blind, randomized, controlled, dose-response, crossover study.

    Science.gov (United States)

    Rodriguez-Mateos, Ana; Feliciano, Rodrigo P; Boeres, Albert; Weber, Timon; Dos Santos, Claudia Nunes; Ventura, M Rita; Heiss, Christian

    2016-10-01

    Cranberries are rich in potentially bioactive (poly)phenols. The aim of this paper was to investigate whether cranberry juice intake can improve vascular function in healthy men in a dose- and time-dependent manner, and to understand which of the circulating (poly)phenol metabolites correlate with vascular effects. A double-blind randomized controlled crossover trial was conducted in ten healthy males. Flow-mediated dilation (FMD), blood pressure, pulse wave velocity and augmentation index were investigated at baseline, 1, 2, 4, 6, and 8 h post-consumption of cranberry juices containing 409, 787, 1238, 1534, and 1910 mg of total cranberry (poly)phenols (TP), and a control drink. Plasma (poly)phenol metabolites were analyzed by UPLC-Q-TOF MS using authentic standards. We observed dose-dependent increases in FMD at 1, 2, 4, 6, and 8 h with a peak at 4 h and maximal effects with juice containing 1238 mg TP. A total of 60 metabolites were quantified in plasma after cranberry consumption. Twelve (poly)phenol metabolites significantly correlated with the increases in FMD, including ferulic and caffeic acid sulfates, quercetin-3-O-ß-D-glucuronide and a γ-valerolactone sulfate. (Poly)phenols in cranberry juice can improve vascular function in healthy males and this is linked to the presence of specific newly identified plasma metabolites. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Eric D Vidoni

    Full Text Available Epidemiological studies suggest a dose-response relationship exists between physical activity and cognitive outcomes. However, no direct data from randomized trials exists to support these indirect observations. The purpose of this study was to explore the possible relationship of aerobic exercise dose on cognition. Underactive or sedentary participants without cognitive impairment were randomized to one of four groups: no-change control, 75, 150, and 225 minutes per week of moderate-intensity semi-supervised aerobic exercise for 26-weeks in a community setting. Cognitive outcomes were latent residual scores derived from a battery of 16 cognitive tests: Verbal Memory, Visuospatial Processing, Simple Attention, Set Maintenance and Shifting, and Reasoning. Other outcome measures were cardiorespiratory fitness (peak oxygen consumption and measures of function functional health. In intent-to-treat (ITT analyses (n = 101, cardiorespiratory fitness increased and perceived disability decreased in a dose-dependent manner across the 4 groups. No other exercise-related effects were observed in ITT analyses. Analyses restricted to individuals who exercised per-protocol (n = 77 demonstrated that Simple Attention improved equivalently across all exercise groups compared to controls and a dose-response relationship was present for Visuospatial Processing. A clear dose-response relationship exists between exercise and cardiorespiratory fitness. Cognitive benefits were apparent at low doses with possible increased benefits in visuospatial function at higher doses but only in those who adhered to the exercise protocol. An individual’s cardiorespiratory fitness response was a better predictor of cognitive gains than exercise dose (i.e., duration and thus maximizing an individual’s cardiorespiratory fitness may be an important therapeutic target for achieving cognitive benefits.ClinicalTrials.gov NCT01129115.

  5. 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

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

    International Nuclear Information System (INIS)

    Burkart, W.

    1981-09-01

    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.)

  7. Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

    International Nuclear Information System (INIS)

    Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Baba-Amer, Yasmine; Tzavara, Eleni; Giros, Bruno; Authier, François-Jérôme; Exley, Christopher; Shaw, Christopher A.; Cadusseau, Josette

    2017-01-01

    Aluminium (Al) oxyhydroxide (Alhydrogel ® ), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180 days after injection of various doses of Alhydrogel ® (200, 400 and 800 μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel ® was observed. Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200 μg Al/kg but not at 400 and 800 μg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200 μg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost Completely disappeared at 6 months in these animals. We conclude that Alhydrogel ® injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose

  8. Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity.

    Science.gov (United States)

    Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Baba-Amer, Yasmine; Tzavara, Eleni; Giros, Bruno; Authier, François-Jérôme; Exley, Christopher; Shaw, Christopher A; Cadusseau, Josette; Gherardi, Romain K

    2017-01-15

    Aluminium (Al) oxyhydroxide (Alhydrogel ® ), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180days after injection of various doses of Alhydrogel ® (200, 400 and 800μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel ® was observed. Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200μg Al/kg but not at 400 and 800μg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200μg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost completely disappeared at 6 months in these animals. We conclude that Alhydrogel ® injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose, but

  9. Effect of sodium nitrite on renal function, sodium and water excretion and brachial and central blood pressure in healthy subjects. A dose-response study

    DEFF Research Database (Denmark)

    Rosenbaek, Jeppe Bakkestroem; Therwani, Safa Al; Jensen, Janni Majgaard

    2017-01-01

    .74, or 3.48 μmol NaNO2/kg/hour for two hours in twelve healthy subjects, after four days standard diet. Subjects were supine and water-loaded. We measured brachial and central blood pressure (BP), plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin (P-AVP), and plasma nitrite...... (P-NO2(-)), GFR by Cr-EDTA clearance, fractional excretion of sodium (FENa) free water clearance (CH2O), and urinary excretion rate of guanosine 3',5'-cyclic monophosphate (U-cGMP). The highest dose reduced brachial systolic BP (5.6 mmHg, p=0.003), central systolic BP (5.6 mmHg, p=0.035) and CH2O...

  10. Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery

    DEFF Research Database (Denmark)

    Poulsen, Troels Dirch; Andersen, Lars Willy; Steinbrüchel, Daniel

    2009-01-01

    . This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB. DESIGN AND SETTING: A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital. PARTICIPANTS: Patients scheduled...

  11. Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study.

    Science.gov (United States)

    Heppner, D Gray; Kemp, Tracy L; Martin, Brian K; Ramsey, William J; Nichols, Richard; Dasen, Emily J; Link, Charles J; Das, Rituparna; Xu, Zhi Jin; Sheldon, Eric A; Nowak, Teresa A; Monath, Thomas P

    2017-08-01

    The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log 10 dose range in two sequential cohorts. In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 10 3 , 3 × 10 4 , 3 × 10 5 , or 3 × 10 6 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 10 6 , 9 × 10 6 , 2 × 10 7 , or 1 × 10 8 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 10 3 [n=64], 3 × 10 4 [n=64], 3 × 10 5 [n=64], or 3 × 10 6 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 10 6 [n=20], 9 × 10 6 [n=47], 2 × 10 7 [n=47], or 1 × 10 8 PFU [n=48]) and 20 received placebo. Most

  12. Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

    Energy Technology Data Exchange (ETDEWEB)

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))

    1990-05-01

    Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.

  13. Cancer dose-response modeling of epidemiological data on worker exposures to aldrin and dieldrin.

    Science.gov (United States)

    Sielken, R L; Bretzlaff, R S; Valdez-Flores, C; Stevenson, D E; de Jong, G

    1999-12-01

    The paper applies classical statistical principles to yield new tools for risk assessment and makes new use of epidemiological data for human risk assessment. An extensive clinical and epidemiological study of workers engaged in the manufacturing and formulation of aldrin and dieldrin provides occupational hygiene and biological monitoring data on individual exposures over the years of employment and provides unusually accurate measures of individual lifetime average daily doses. In the cancer dose-response modeling, each worker is treated as a separate experimental unit with his own unique dose. Maximum likelihood estimates of added cancer risk are calculated for multistage, multistage-Weibull, and proportional hazards models. Distributional characterizations of added cancer risk are based on bootstrap and relative likelihood techniques. The cancer mortality data on these male workers suggest that low-dose exposures to aldrin and dieldrin do not significantly increase human cancer risk and may even decrease the human hazard rate for all types of cancer combined at low doses (e.g., 1 microgram/kg/day). The apparent hormetic effect in the best fitting dose-response models for this data set is statistically significant. The decrease in cancer risk at low doses of aldrin and dieldrin is in sharp contrast to the U.S. Environmental Protection Agency's upper bound on cancer potency based on mouse liver tumors. The EPA's upper bound implies that lifetime average daily doses of 0.0000625 and 0.00625 microgram/kg body weight/day would correspond to increased cancer risks of 0.000001 and 0.0001, respectively. However, the best estimate from the Pernis epidemiological data is that there is no increase in cancer risk in these workers at these doses or even at doses as large as 2 micrograms/kg/day.

  14. Dairy consumption and risk of stroke: A systematic review and updated dose-response meta-analysis of prospective cohort studies

    NARCIS (Netherlands)

    Goede, de J.; Soedamah-Muthu, S.S.; Pan, An; Gijsbers, L.; Geleijnse, J.M.

    2016-01-01

    Background
    A higher milk consumption may be associated with a lower stroke risk. We conducted a comprehensive systematic review and dose–response meta‐analysis of milk and other dairy products in relation to stroke risk.

    Methods and Results
    Through a systematic literature search,

  15. Dose-response relationships in normal tissues and their evaluation

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Tanaka, Yoshiaki; Matsui, Masanori

    1990-01-01

    Radiotherapeutic effects can be defined as the ratio of radiation injuries in normal tissues to in cancer tissues. Much more attention has been paid to refractory delayed reaction rather than early reaction to normal tissues. Focusing on the reevaluation of the Rubin's and Casarett's data concerning delayed injuries in the cerebrospinal nerves, gastrointestinal organ, and lung tissues, this chapter compares tolerance doses of low LET radiation with those of high LET radiation, and discusses how normal tissue reaction is modified by the combination of antineoplastic agents, radiosensitizers, and/or hyperthermia. An effort is also made here to reevaluate daily hyperfractionation from the basic and clinical points of view. The information is allocated into the following 12 subjects: (1) radiation injury of the normal brain tissue after external radiotherapy for brain tumor; (2) treatment policies with active intention for brain tumor and tolerance doses for the nervous system; (3) radiation enteritis - mucosal regeneration and stromal reaction of the small intestine after irradiation; (4) tolerance doses for the small intestine and colon in carcinoma of the uterine cervix; (5) radiation tolerance of the normal lung - pulmonary radiation syndromes; (6) clinical study on development factors of radiation pneumonitis; (7) effect of repeated small doses of radiation on cell killing and repair capacity in plateau phase C3H10T1/2 cells; (8) fractionation and radiation injury - clinical aspect; (9) normal tissue tolerance to high LET radiotherapy; (10) tolerance doses for normal tissues by radiotherapy combined with chemotherapy in patients; (11) radiosensitization of mouse intestinal epithelial cells with BrdR; (12) arterial blood flow changes after hyperthermia in the normal liver, brain, and small intestine. (N.K.)

  16. Influence of dose history on thermoluminescence response of Ge-doped silica optical fibre dosimeters

    International Nuclear Information System (INIS)

    Moradi, F.; Mahdiraji, G.A.; Dermosesian, E.; Khandaker, M.U.; Ung, N.M.; Mahamd Adikan, F.R.; Amin, Y.M.

    2017-01-01

    Nowadays, silica based optical fibres show enough potential to be used as TL dosimeters in different applications. Reuse of optical fibre as a practical dosimeter demands to complete removal of accumulated doses via previous irradiations. This work investigates the existence and/or effect of remnant doses in fibre dosimeter from the previous irradiations, and proposes a method to control this artifact. A single mode Ge-doped optical fibre is used as TL radiation sensor, while a well calibrated Gammacell with 60 Co source is used for irradiations. The effect of irradiation history on the TL response of optical fibres is surveyed extensively for doses ranged from 1 to 1000 Gy. The results show that the absorbed dose history in a fibre affects its response in the next irradiation cycles. It is shown that a dose history of around 100 Gy can increase the response of optical fibre by a factor of 1.72. The effect of annealing at higher temperatures on stabilizing the fibre response is also examined and results revealed that another alteration in the structure of trapping states occurs in glass medium which can change the sensitivity of fibres. Preservation of the sensitivity during successive irradiation cycles can be achieved by a proper annealing procedure accompanied by a pre-dose treatment. - Highlights: • Influence of dose history on TL characteristics of fibre dosimeter is explored. • The phenomenon behind the TL variation caused by dose history is discussed. • Effect of annealing temperature on performance of fibre dosimeter is studied. • Pre-treatment methods for mitigating variation in reproducibility are proposed.

  17. Effect of increased CRM₁₉₇ carrier protein dose on meningococcal C bactericidal antibody response.

    Science.gov (United States)

    Lee, Lucia H; Blake, Milan S

    2012-04-01

    New multivalent CRM(197)-based conjugate vaccines are available for childhood immunization. Clinical studies were reviewed to assess meningococcal group C (MenC) antibody responses following MenC-CRM(197) coadministration with CRM(197)-based pneumococcal or Haemophilus influenzae type b conjugate vaccines. Infants receiving a total CRM(197) carrier protein dose of ∼50 μg and concomitant diphtheria-tetanus-acellular pertussis (DTaP)-containing vaccine tended to have lower MenC geometric mean antibody titers and continued to have low titers after the toddler dose. Nevertheless, at least 95% of children in the reported studies achieved a MenC serum bactericidal antibody (SBA) titer of ≥ 1:8 after the last infant or toddler dose. SBA was measured using an assay with a baby rabbit or human complement source. Additional studies are needed to assess long-term antibody persistence and MenC CRM(197) conjugate vaccine immunogenicity using alternative dosing schedules.

  18. The high dose response of silicon carbide MESFET

    International Nuclear Information System (INIS)

    Brisset, C.; Picard, C.; Joffre, F.; Noblanc, O.; Brylinski, C.

    1999-01-01

    The performance of MESFET-SiC transistors submitted to 60 Co gamma radiation has been studied. MESFETs irradiated in the passing mode present a satisfactorily behaviour till cumulated dose below 10 MGy(Si). The off-state operating mode is the most unfavourable, in this case a complete loss of functionality was observed, followed by a slow comeback to an almost normal functioning after several months of rest. (A.C.)

  19. Relationship of dose rate and total dose to responses of continuously irradiated beagles

    International Nuclear Information System (INIS)

    Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

    1978-01-01

    Young-adult beagles were exposed continuously (22 hours/day) to 60 Co gamma rays in a specially constructed facility. The exposure rates were 5, 19, 17 or 35 R/day, and the exposures were terminated at 600, 1400, 2000 or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for gamma-ray exposures given at a number of exposure rates. They also allow comparison of the relativeimportance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 344 R (258 rads) delivered at 15 R/minute to approximately 4000 R (approximately 3000 rads) at 10 R/day. Over this entire range, the LD 50 is dependent upon haematopoietic damage. At 5 R/day and less, no definitive LD 50 can be determined; there is nearly normal continued haematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in the organ systems. Although the experiment is not complete, interim data allow serveral important conclusions. Terminated exposures, while not as effective as irradiation continued until death, can produce myelogenous leukaemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates appear more damaging than higher rates on the basis of the rate and degree of haematological recovery that occurs after termination of irradiation. Thus, the rate of haematologic depression, the nadir of the depression and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the first two are directly related to exposure rate. ( author)

  20. Relationship of dose rate and total dose to responses of continuously irradiated beagles

    International Nuclear Information System (INIS)

    Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

    1978-01-01

    Young-adult beagles were exposed continuously (22 hours/day) to 60 Co γ rays in a specially constructed facility. The exposure rates were either 5, 10, 17, or 35 R/day, and the exposures were terminated at either 600, 1400, 2000, or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for γ-ray exposures given at a number of exposure rates. They also allow comparison of the relative importance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 258 rad delivered at 15 R/minute to approximately 3000 rad at 10 R/day. Over this entire range, the LD 50 is dependent upon hematopoietic damage. At 5 R/day and less, no meaningful LD 50 can be determined; there is nearly normal continued hematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in other organ systems. Although the experiment is not complete, interim data allow several important conclusions. Terminated exposures, while not as effective as radiation continued until death, can produce myelogenous leukemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates are more damaging than higher rates on the basis of the rate and degree of hematological recovery that occurs after termination of irradiation. Thus, the rate of hematologic depression, the nadir of the depression, and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the former two are directly related to exposure rate

  1. Persistence of Meningococcal Antibodies and Response to a Third Dose After a Two-dose Vaccination Series with Investigational MenABCWY Vaccine Formulations in Adolescents.

    Science.gov (United States)

    Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Han, Linda; Smolenov, Igor; Dull, Peter

    2015-10-01

    In a primary study, healthy adolescents received 2 doses (months 0/2) of 1 of the 4 investigational meningococcal ABCWY vaccine formulations, containing components of licensed quadrivalent glycoconjugate vaccine MenACWY-CRM, combined with different amounts of recombinant proteins (rMenB) and outer membrane vesicles (OMV) from a licensed serogroup B vaccine, or 2 doses of rMenB alone or 1 dose of MenACWY-CRM then a placebo. This phase 2 extension study evaluated antibody persistence up to 10 months after the 2-dose series and the immunogenicity and safety of a third dose (month 6). Immune responses against serogroups ACWY and serogroup B test strains were measured by serum bactericidal assay with human complement. At month 12, antibody persistence against serogroups ACWY in all 2-dose MenABCWY groups was at least comparable with the 1-dose MenACWY-CRM group. Bactericidal antibodies against most serogroup B test strains declined by month 6, then plateaued over the subsequent 6 months, with overall higher antibody persistence associated with OMV-containing formulations. A third MenABCWY vaccine dose induced robust immune responses against vaccine antigens, although antibody levels 6 months later were comparable with those observed 5 months after the 2-dose series. All investigational MenABCWY vaccines were well tolerated. Two or three doses of investigational MenABCWY vaccines elicited immune responses against serogroups ACWY that were at least comparable with those after 1 dose of MenACWY-CRM. After either vaccination series, investigational MenABCWY vaccine formulations containing OMV had the highest immunogenicity against most serogroup B test strains. No safety concerns were identified in this study.

  2. Neuromuscular responses to incremental caffeine doses: performance and side effects.

    Science.gov (United States)

    Pallarés, Jesús G; Fernández-Elías, Valentín E; Ortega, Juan F; Muñoz, Gloria; Muñoz-Guerra, Jesús; Mora-Rodríguez, Ricardo

    2013-11-01

    The purpose of this study was to determine the oral dose of caffeine needed to increase muscle force and power output during all-out single multijoint movements. Thirteen resistance-trained men underwent a battery of muscle strength and power tests in a randomized, double-blind, crossover design, under four different conditions: (a) placebo ingestion (PLAC) or with caffeine ingestion at doses of (b) 3 mg · kg(-1) body weight (CAFF 3mg), (c) 6 mg · kg(-1) (CAFF 6mg), and (d) 9 mg · kg(-1) (CAFF 9mg). The muscle strength and power tests consisted in the measurement of bar displacement velocity and muscle power output during free-weight full-squat (SQ) and bench press (BP) exercises against four incremental loads (25%, 50%, 75%, and 90% one-repetition maximum [1RM]). Cycling peak power output was measured using a 4-s inertial load test. Caffeine side effects were evaluated at the end of each trial and 24 h later. Mean propulsive velocity at light loads (25%-50% 1RM) increased significantly above PLAC for all caffeine doses (5.4%-8.5%, P = 0.039-0.003). At the medium load (75% 1RM), CAFF 3mg did not improve SQ or BP muscle power or BP velocity. CAFF 9mg was needed to enhance BP velocity and SQ power at the heaviest load (90% 1RM) and cycling peak power output (6.8%-11.7%, P = 0.03-0.05). The CAFF 9mg trial drastically increased the frequency of the adverse side effects (15%-62%). The ergogenic dose of caffeine required to enhance neuromuscular performance during a single all-out contraction depends on the magnitude of load used. A dose of 3 mg · kg(-1) is enough to improve high-velocity muscle actions against low loads, whereas a higher caffeine dose (9 mg · kg(-1)) is necessary against high loads, despite the appearance of adverse side effects.

  3. Biological profiling and dose-response modeling tools ...

    Science.gov (United States)

    Through its ToxCast project, the U.S. EPA has developed a battery of in vitro high throughput screening (HTS) assays designed to assess the potential toxicity of environmental chemicals. At present, over 1800 chemicals have been tested in up to 600 assays, yielding a large number of concentration-response data sets. Standard processing of these data sets involves finding a best fitting mathematical model and set of model parameters that specify this model. The model parameters include quantities such as the half-maximal activity concentration (or “AC50”) that have biological significance and can be used to inform the efficacy or potency of a given chemical with respect to a given assay. All of this data is processed and stored in an online-accessible database and website: http://actor.epa.gov/dashboard2. Results from these in vitro assays are used in a multitude of ways. New pathways and targets can be identified and incorporated into new or existing adverse outcome pathways (AOPs). Pharmacokinetic models such as those implemented EPA’s HTTK R package can be used to translate an in vitro concentration into an in vivo dose; i.e., one can predict the oral equivalent dose that might be expected to activate a specific biological pathway. Such predicted values can then be compared with estimated actual human exposures prioritize chemicals for further testing.Any quantitative examination should be accompanied by estimation of uncertainty. We are developing met

  4. RadFET dose response in the CHARM mixed-field: FLUKA MC simulations

    Directory of Open Access Journals (Sweden)

    Marzo Matteo

    2017-01-01

    Full Text Available This paper focuses on Monte Carlo simulations aimed at calculating the dose response of the RadFET dosimeter, when exposed to the complex CHARM mixed-fields, at CERN. We study how the dose deposited in the gate oxide (SiO2 of the RadFET is affected by the energy threshold variation in the Monte Carlo simulations as well as the materials and sizes of scoring volumes. Also the characteristics of the input spectra will be taken into account and their impact on the final simulated dose will be studied. Dose variation as a function of the position of the RadFET in the test facility will be then examined and comparisons with experimental results will be shown. The contribution to the total dose due to all particles of the mixed-field, under different target-shielding configurations, is finally presented, aiming at a complete characterization of the RadFETs dose response in the CHARM mixed-fields.

  5. RadFET dose response in the CHARM mixed-field: FLUKA MC simulations

    Directory of Open Access Journals (Sweden)

    Marzo M.

    2017-01-01

    Full Text Available This paper focuses on Monte Carlo simulations aiming at calculating the dose response of the Rad- FET dosimeter, when exposed to the complex CHARM mixed-fields, at CERN. We study how the dose deposited in the Gate Oxide (SiO2 of the RadFET is a_ected by the energy threshold variation in the Monte Carlo simulations as well as the materials and sizes of scoring volumes. Also the characteristics of the input spectra will be taken into account and their impact on the final simulated dose will be studied. Dose variation as a function of the position of the RadFET in the test facility will be then examined and comparisons with experimental results will be shown. The contribution to the total dose due to every single particles of the mixed-field, under di_erent target-shielding configurations, will be finally presented, aiming at a complete characterization of the RadFETs dose response in the CHARM mixed-fields.

  6. A Meta-Analysis To Determine the Dose Response for Strength Development.

    Science.gov (United States)

    Rhea, Matthew R.; Alvar, Brent A.; Burkett, Lee N.; Ball, Stephen D.

    2003-01-01

    Examined the quantitative dose-response relationship for strength development by calculating the magnitude of gains elicited by various levels of training intensity, frequency, and volume; thus clarifying the effort to benefit ratio. A meta-analysis of 140 studies with 1,433 effect sizes (ES) was conducted. ES demonstrated different responses…

  7. 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

  8. Lack-of-fit tests for assessing mean structures for continuous dose-response data

    DEFF Research Database (Denmark)

    Ritz, Christian; Martinussen, Torben

    2011-01-01

    that the classical methods are inadequate in certain situations, where the new tests may be applied. Power comparisons are carried out by means of extensive simulation studies, covering both designs with and without replicates at small and large sample sizes. Three datasets from dose-response applications illustrate...

  9. The time-dose-response relationship for elicitation of contact dermatitis in isoeugenol allergic individuals

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Johansen, Jeanne Duus; Bruze, M

    2001-01-01

    The elicitation response in allergic contact dermatitis is dose dependent, but the time-concentration relationship for elicitation has not previously been described. In this study 27 isoeugenol-sensitive patients participated in serial dilution patch tests with isoeugenol and a double-blinded Rep...

  10. Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers

    NARCIS (Netherlands)

    Ronckers, Cécile M.; Sigurdson, Alice J.; Stovall, Marilyn; Smith, Susan A.; Mertens, Ann C.; Liu, Yan; Hammond, Sue; Land, Charles E.; Neglia, Joseph P.; Donaldson, Sarah S.; Meadows, Anna T.; Sklar, Charles A.; Robison, Leslie L.; Inskip, Peter D.

    2006-01-01

    Radiation exposure at a young age is a strong risk factor for thyroid cancer. We conducted a nested case-control study of 69 thyroid cancer cases and 265 controls from a cohort of 14,054 childhood cancer survivors to evaluate the shape of the radiation dose-response relationship, in particular at

  11. Confidence bounds for nonlinear dose-response relationships

    DEFF Research Database (Denmark)

    Baayen, C; Hougaard, P

    2015-01-01

    . 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...

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

    International Nuclear Information System (INIS)

    Rowland, R.E.; Stehney, A.F.; Lucas, H.F. Jr.

    1981-01-01

    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#D 2 )e/sup -#betta#D/, and simplifications of this general form, were fit to each data set. Two functions, I = (C + αD + #betta#D 2 )e/sup -#betta#D/ and I = (C + #betta#D 2 )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#D 2 )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

  13. Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am

    International Nuclear Information System (INIS)

    DuFrain, R.J.; Littlefield, L.G.; Joiner, E.E.; Frome, E.L.

    1979-01-01

    Cytogenetic dosimetry estimates to guide treatment of persons internally contaminated with transuranic elements have not previously been possible because appropriate in vitro dose-response curves specifically for alpha particle irradiation of human lymphocytes do not exist. Using well-controlled cytogenetic methods for human lymphocyte culture, an experimentally derived dose-response curve for 241 Am alpha particle (5.49 and 5.44 MeV) radiation of G 0 lymphocytes was generated. Cells were exposed to 43.8, 87.7, 175.3 or 350.6 nCi/ml 241 Am for 1.7 hr giving doses of 0.85, 1.71, 3.42 or 6.84 rad. Based on dicentric chromosome yield, the linear dose-response equation is Y = 4.90(+-0.42) x 10 -2 X, with Y given as dicentrics per cell and X as dose in rads. The study also shows that the two-break asymmetrical exchanges in cells damaged by alpha particle radiation are overdispersed when compared to a Poisson distribution. An example is presented to show how the derived dose-response equation can be used to estimate the radiation dose for a person internally contaminated with an actinide. An experimentally derived RBE value of 118 at 0.85 rad is calculated for the efficiency of 241 Am alpha particle induction of dicentric chromosomes in human G 0 lymphocytes as compared with the efficiency of 60 Co gamma radiation. The maximum theoretical value for the RBE for cytogenetic damage from alpha irradiation was determined to be 278 at 0.1 rad or less which is in marked contrast to previously reported RBE values of approx. 20. (author)

  14. Dose response on the 110 °C thermoluminescence peak of un-heated, synthetic Merck quartz

    Energy Technology Data Exchange (ETDEWEB)

    Kaya Keleş, Şule, E-mail: sule.kaya@ankara.edu.tr; Meriç, Niyazi; Polymeris, George S.

    2016-07-15

    Studies on 110 °C TL peak have been carried out using natural quartz from different origins and synthetic quartz produced by different suppliers. The interest in quartz is due to its usage in dating and retrospective dosimetry as a main material; both synthetic and natural types of quartz yield the 110 °C TL peak in their glow curve. In most studies to understand the physical mechanism behind the TL system, synthetic quartz samples are used and there are many investigations about dose response, in both low and high radiation dose region. In these studies generally synthetic quartz samples produced by Sawyer Research Products are used and the studies showed that both heated and un-heated synthetic quartz samples have intense supra-linear responses. Supra-linearity was enhanced by applying a pre-irradiation while several models have been developed towards an explanation to these supra-linearity effects. In this study commercially available synthetic Merck quartz was used. Different combinations of optical filters were used to obtain dose response curves upto 266 Gy and the effect of pre-dose to these dose response curves was studied. Un-pre-dosed Merck quartz samples dose supra-linearity index is below 1 independently on the optical filters; so Merck quartz showed linear or sub-linear dose response.

  15. Cellular response to low dose radiation: Role of phosphatidylinositol-3 kinase like kinases

    Energy Technology Data Exchange (ETDEWEB)

    Balajee, A.S.; Meador, J.A.; Su, Y.

    2011-03-24

    differences in cellular defense mechanisms between low and high doses of low LET radiation and to define the radiation doses where the cellular DNA damage signaling and repair mechanisms tend to shift. This information is critically important to address and advance some of the low dose research program objectives of DOE. The results of this proposed study will lead to a better understanding of the mechanisms for the cellular responses to low and high doses of low LET radiation. Further, systematic analysis of the role of PIKK signaling pathways as a function of radiation dose in tissue microenvironment will provide useful mechanistic information for improving the accuracy of radiation risk assessment for low doses. Knowledge of radiation responses in tissue microenvironment is important for the accurate prediction of ionizing radiation risks associated with cancer and tissue degeneration in humans.

  16. Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

    Science.gov (United States)

    Paterna, Salvatore; Di Gaudio, Francesca; La Rocca, Vincenzo; Balistreri, Fabio; Greco, Massimiliano; Torres, Daniele; Lupo, Umberto; Rizzo, Giuseppina; di Pasquale, Pietro; Indelicato, Sergio; Cuttitta, Francesco; Butler, Javed; Parrinello, Gaspare

    2015-10-01

    Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0-24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24-48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and

  17. Use of a Dose-Response Model to Study Temporal Trends in Spatial Exposure to Coxiella burnetii : Analysis of a Multiyear Outbreak of Q Fever

    NARCIS (Netherlands)

    Brooke, R J; Teunis, P F M; Kretzschmar, M E E; Wielders, C C H; Schneeberger, P M; Waller, L A

    The Netherlands underwent a large Q fever outbreak between 2007 and 2009. In this paper, we study spatial and temporal Coxiella burnetii exposure trends during this large outbreak as well as validate outcomes against other published studies and provide evidence to support hypotheses on the causes of

  18. Bone cancer from radium: canine dose response explains data for mice and humans

    International Nuclear Information System (INIS)

    Raabe, O.G.; Book, S.A.; Parks, N.J.

    1980-01-01

    Analysis of lifetime studies of 243 beagles with skeletal burdens of radium-226 shows that the distribution of bone cancers clusters about a linear function of the logarithms of radiation dose rate to the skeleton and time from exposure until death. Similar relations displaced by species-dependent response ratios also provide satisfactory descriptions of the reported data on deaths from primary bone cancers in people and mice exposed to radium-226. The median cumulative doses (or times) leading to death from bone tumors are 2.9 times larger for dogs than for mice and 3.6 times larger for people than for dogs. These response ratios are well correlated with the normal life expectancies. The cumulative radiation dose required to give significant risk of bone cancer is found to be much less at lower dose rates than at higher rates, but the time required for the tumors to be manifested is longer. At low dose rates, this time exceeds the normal life-span and appears as a practical threshold, which for bone cancer is estimated to occur at an average cumulative radiation dose to the skeleton of about 50 to 110 rads for the three species

  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 lectures to present the current state of the science of EDC action and also the risk assessment process. These lectures were followed by breakout sessions to integrate scientists from various backgrounds to discuss in an open and unbiased manner the data supporting the “low dose hypothesis”. While...

  20. Adaptive response of yeast cultures (Saccharomyces Cerevisiae) exposed to low dose of gamma radiation

    International Nuclear Information System (INIS)

    Kulcsar, Agnes; Savu, D.; Petcu, I.; Gherasim, Raluca

    2003-01-01

    The present study was planned as follows: (i) setting up of standard experimental conditions for investigation of radio-induced adaptive response in lower Eucaryotes; (ii) developing of procedures for synchronizing Saccharomyces cerevisiae X 310 D cell cultures and cell cycle stages monitoring; (iii) investigation of gamma (Co-60) and UV irradiation effects on the viability of synchronized and non-synchronized cell cultures of Saccharomyces cerevisiae; the effects were correlated with the cell density and cell cycle stage; (iv) study of the adaptive response induced by irradiation and setting up of the experimental conditions for which this response is optimized. The irradiations were performed by using a Co-60 with doses of 10 2 - 10 4 Gy and dose rates ranging from 2.2 x 10 2 Gy/h to 8.7 x 10 3 Gy/h. The study of radioinduced adaptive response was performed by applying a pre-irradiation treatment of 100-500 Gy, followed by challenge doses of 2-4 kGy delivered at different time intervals, ranging from 1 h to 4 h. The survival rate of synchronized and non-synchronized cultures as a function of exposure dose shows an exponential decay shape. No difference in viability of the cells occurred between synchronized and non-synchronized cultures. The pre-irradiation of cells with 100 and 200 Gy were most efficient to induce an adaptive response for the yeast cells. In this stage of work we proved the occurrence of the adaptive response in the case of synchronized yeast cultures exposed to gamma radiation. The results will be used in the future to investigate the dependence of this response on the cell cycle and the possibility to induce such a response by a low level electromagnetic field. (authors)

  1. Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma.

    Science.gov (United States)

    Matsumoto, Koichiro; Aizawa, Hisamichi; Fukuyama, Satoru; Yoshida, Makoto; Komori, Masashi; Takata, Syohei; Koto, Hiroshi; Inoue, Hiromasa

    2013-09-01

    Airway hyperresponsiveness is a cardinal feature of asthma. Although the modulation of cholinergic neuroeffector transmission may play a role in airway responsiveness, in vivo evidence remains scarce. It is well known that histamine causes bronchoconstriction partly via vagal reflex, whereas methacholine does not. To investigate the significance of modulating neuroeffector transmission, we compared the effect of low-dose salbutamol-a β2-adrenoceptor agonist-on airway responsiveness to histamine with that to methacholine. We enrolled 12 subjects with stable asthma. After screening confirmed that inhalation of low-dose salbutamol (1μg) did not change their basic pulmonary function, subjects underwent measurement of airway responsiveness to inhaled histamine and methacholine with or without pretreatment with low-dose salbutamol, in a randomized, crossover fashion. Airway responsiveness was measured by an astograph by which respiratory conductance (Grs) was assessed by the forced oscillation method during continuous inhalation of histamine or methacholine in stepwise incremental concentrations. Airway responsiveness was calculated as the cumulative dose of bronchoconstrictors that induced a decrease of 35% in Grs. Inhalation of 1μg of salbutamol significantly attenuated airway responsiveness to histamine but not methacholine. This selective attenuation was observed irrespective of disease severity or phenotype, namely atopy or non-atopy. Low-dose salbutamol suppresses airway responsiveness to histamine but not methacholine in subjects with asthma. The present study may provide a novel insight into the bronchoprotective mechanism of β2-adorenoceptor agonist in clinical settings. © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  2. Exposure to Nitrogen Oxide in the First Trimester and Risk of Cardiovascular-Related Malformations: A Dose-Response Meta-Analysis of Observational Studies

    Directory of Open Access Journals (Sweden)

    Tie-Ning Zhang

    2018-01-01

    Full Text Available Nitrogen oxide (NOx is produced during combustion at high temperature, which is a major constituent of air pollutants. Recent studies suggested inconsistent results on the association between NOx exposure and cardiovascular-related malformations. We aimed to assess aforementioned association in pregnant women in the first trimester and cardiovascular-related malformations of infants. A systematic literature review identified studies for observational studies about NOx exposure and cardiovascular-related malformation in PubMed. Random-effect models were used to estimate summary odds ratio (SOR and 95% confidence intervals (CIs for aforementioned association. Finally, nine studies met the inclusion criteria. Overall, the SOR of cardiovascular-related malformation per 10 ppb increment in NOx and NO2 concentration was 1.01 (95% CI: 0.98–1.04; I2 = 38.6%, P=0.09 and 0.99 (95% CI: 0.95–1.04; I2 = 37.8%, P=0.13, respectively. Stratifying by study design, geographic locations, and confounded adjustments, the majority of strata showed negative results, which were consistent with the main findings. However, we found that exposure to NOx and NO2 in the first trimester increased the risk of coarctation of the aorta (COA malformation by 13% and 19%, respectively. Our study provided limited evidence regarding the association between NOx exposure in the first trimester and cardiovascular-related malformations in infants.

  3. Influence of parental health literacy and dosing responsibility on pediatric glaucoma medication adherence.

    Science.gov (United States)

    Freedman, Rebecca B; Jones, Sarah K; Lin, Alice; Robin, Alan L; Muir, Kelly W

    2012-03-01

    To assess glaucoma medication adherence in children, hypothesizing that poor parental health literacy and eye drop instillation by the child are associated with worse adherence. This prospective, observational study enrolled pediatric patients with glaucoma who were prescribed eye drops. Parent(s) reported who was responsible for eye drop instillation (parent vs child), took the Rapid Estimate of Adult Literacy in Medicine, and were instructed on the use and purpose of the Medication Event Monitoring System. Calculations included average adherence (proportion of prescribed doses taken), dosing errors (number of overdosing or underdosing events in 24 hours), and proportion of doses taken on schedule (doses taken within 2 hours of prescribed dosing interval). Results are reported as mean (SD) or median. The study included 46 of the 50 enrolled children who used the Medication Event Monitoring System for 30 days or more. Adherence ranged from 43% to 107% (93% [12%]) and was not associated with age (slope, 0.09 [0.52]; P = .86) but decreased with the parent's lower health literacy (slope, 0.62 [0.24]; P = .01).The mean number of dosing errors for medications prescribed daily vs twice daily was similar (3.3 vs 2.9; P = .66). The proportion of doses taken on schedule (within 2 hours of prescribed dosing interval) ranged from 3% to 97% (median, 34%; mean, 41% [24%]) and was better when the parent vs the child instilled eye drops (46% [26%] vs 23% [19%]; P responsible for eye drop instillation. Overall decreased adherence was associated with decreased parental health literacy. Children of parents with poor health literacy are vulnerable to poor medication adherence; efforts to address poor health literacy may improve outcomes.

  4. 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.

  5. INFLUENCE OF DOSE RATE ON THE CELLULAR RESPONSE TO LOW- AND HIGH-LET RADIATIONS

    Directory of Open Access Journals (Sweden)

    Anne-Sophie eWozny

    2016-03-01

    Full Text Available Nowadays, head and neck squamous cell carcinoma (HNSCC treatment failure is mostly explained by loco-regional progression or intrinsic radioresistance. Radiotherapy has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy which modify the dose-rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional radiotherapy or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient. In this regard, two HNSCC cell lines were irradiated with photons or 72MeV/n carbon ions at a dose rate of 0.5, 2 or 10Gy/min.For both radiosensitive and radioresistant cells, the change in dose rate significantly affected cell survival in response to photon exposure, this variation of radiosensitivity was associated to the number of initial and residual DNA double-strand breaks. By contrast, the dose rate change did not affect neither cell survival nor the residual DNA double-strand breaks after carbon ion irradiation. As a result, the Relative Biological Efficiency at 10% survival increased when the dose rate decreased.In conclusion, in the radiotherapy treatment of HNSCC, it is advised to remain very careful when modifying the classical schemes towards altered-fractionation. At the opposite, as the dose rate does not seem to have any effects after carbon ion exposure, there is less need to adapt hadrontherapy treatment planning during active system irradiation

  6. Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis

    Science.gov (United States)

    Chappelli, Lori J.; Cucinotta, Francis A.

    2010-01-01

    BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data

  7. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

    Science.gov (United States)

    Blumberg, Jeffrey B.; Vita, Joseph A.; Chen, C. -Y. Oliver

    2015-01-01

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages. PMID:26633488

  8. Graphic display of radiobiological effects on dose response models and its application for clinical optimization

    International Nuclear Information System (INIS)

    Aoki, Yukimasa; Onogi, Yuzou; Nakagawa, Keiichi; Akanuma, Atsuo; Iio, Masahiro; Sakata, Kouichi; Karasawa, Katsuyuki; Kaneko, Katsutaro.

    1988-01-01

    Both physical dose distribution and radiobiological effect should be required for radiotherapy optimization, however, there is a tendency that they are handled separately and that the former is processed in the shape of dose distribution and the latter is estimated quantitatively as point values. Those two parameters are combined in the iso-TDF map, where various responses of organs are not considered. In this study, the iso-effect distribution and the dose distributions are compared to investigate optimization for radiation treatment. A computer program is developed to construct an image of iso-effect from both various response values of internal organs and a certain physical dose and to show the integral value of certain region of interest. NSD-TDF model and LQ model are adopted and presumptive cases of esophagus cancer and pituitary tumor are employed. The results show that the effect to normal tissues increases with one port a day technique compared with plural ports a day technique and the latter is most preferable in both cases. It will require a proper weighting function to establish a generalized parameter for both spatial and chronological optimization by integrating dose and biological effect. The volume effect in biological responses will be argued with three dimensional implementation of this program. (author)

  9. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships.

    Science.gov (United States)

    Blumberg, Jeffrey B; Vita, Joseph A; Chen, C-Y Oliver

    2015-12-02

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages.

  10. Dose-response association between leisure time physical activity and work ability

    DEFF Research Database (Denmark)

    Calatayud, Joaquin; Jakobsen, Markus D; Sundstrup, Emil

    2015-01-01

    INTRODUCTION: Regular physical activity is important for longevity and health, but knowledge about the optimal dose of physical activity for maintaining good work ability is unknown. This study investigates the association between intensity and duration of physical activity during leisure time......, lifestyle and chronic disease showed that the duration of high-intensity physical activity during leisure was positively associated with work ability, in a dose-response fashion (p physical activity per week had on average 8 points higher work ability...... than those not performing such activities. The duration of low-intensity leisure-time physical activity was not associated with work ability (p = 0.5668). CONCLUSIONS: The duration of high-intensity physical activity during leisure time is associated in a dose-response fashion with work ability...

  11. Radiation dose-response curves: cell repair mechanisms vs. ion track overlapping

    Science.gov (United States)

    Kowalska, Agata; Czerski, Konrad; Nasonova, Elena; Kutsalo, Polina; Krasavin, Eugen

    2017-12-01

    Chromosome aberrations in human lymphocytes exposed to different doses of particle radiation: 150 MeV and spread out Bragg peak proton beams, 22 MeV/u boron beam and 199 V/u carbon beam were studied. For comparison, an experiment with 60Co γ-rays was also performed. We investigated distributions of aberration frequency and the shape of dose-response curves for the total aberration yield as well as for exchange and non-exchange aberrations, separately. Applying the linear-quadratic model, we could derive a relation between the fitted parameters and the ion track radius which could explain experimentally observed curvature of the dose-response curves. The results compared with physical expectations clearly show that the biological effects of cell repair are much more important than the ion track overlapping. Contribution to the Topical Issue "Dynamics of Systems at the Nanoscale", edited by Andrey Solov'yov and Andrei Korol.

  12. Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies

    NARCIS (Netherlands)

    Aune, D.; Chan, D.S.; Lau, R.; Vieira, R.; Greenwood, D.C.; Kampman, E.; Norat, T.

    2011-01-01

    OBJECTIVE: To investigate the association between intake of dietary fibre and whole grains and risk of colorectal cancer. DESIGN: Systematic review and meta-analysis of prospective observational studies. DATA SOURCES: PubMed and several other databases up to December 2010 and the reference lists of

  13. Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies

    NARCIS (Netherlands)

    Aune, D.; Chan, D.S.M.; Lau, R.; Vieira, R.; Greenwood, D.C.; Kampman, E.; Norat, T.

    2011-01-01

    Objective To investigate the association between intake of dietary fibre and whole grains and risk of colorectal cancer. Design Systematic review and meta-analysis of prospective observational studies. Data sources PubMed and several other databases up to December 2010 and the reference lists of

  14. What can be learned from epidemiologic studies of persons exposed to low doses of radiation?

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1993-04-01

    The main objective of radiation risk assessment is to determine the risk of various adverse health effects associated with exposure to low doses and low dose rates. Extrapolation of risks from studies of persons exposed at high doses (generally exceeding 1 Sv) and dose rates has been the primary approach used to achieve this objective. The study of Japanese atomic bomb survivors in Hiroshima and Nagasaki has played an especially important role in risk assessment efforts. A direct assessment of the dose-response function based on studies of persons exposed at low doses and dose rates is obviously desirable. This paper focuses on the potential of both current and future nuclear workers studies for investigating the dose-response functions at low doses, and also discusses analyses making use of the low dose portion of the atomic bomb survivor data. Difficulties in using these data are the statistical imprecision of estimated dose-response parameters, and potential bias resulting from confounding factors and from uncertainties in dose estimates

  15. Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation

    Science.gov (United States)

    Limoli, C. L.; Corcoran, J. J.; Milligan, J. R.; Ward, J. F.; Morgan, W. F.

    1999-01-01

    To investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.

  16. Dose-response Relationship of Serum Uric Acid with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease Incidence: A Meta-analysis of Prospective Studies.

    Science.gov (United States)

    Liu, Zhengtao; Que, Shuping; Zhou, Lin; Zheng, Shusen

    2015-09-23

    Emerging evidence has shown that serum uric acid (SUA) elevation might cause metabolic derangements, including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD); however, magnitude of the risk has not been quantified. We searched PubMed, EMBASE, and ISI databases for relevant studies through 10 May 2015. Prospective studies reporting the risk of SUA elevation on the incidence of MetS/NAFLD were enrolled. Pooled HR of MetS was 1.55 (95%CI: 1.40-1.70) for the highest versus lowest SUA categories, and 1.05 (95%CI: 1.04-1.07) per incremental increased in SUA of 1 mg/dl. The pooled HR of MetS in younger women was higher than age-matched men and older women (1.17 vs. 1.05 and 1.04, respectively, P metabolic disorders for linear trend between its elevation and MetS/NAFLD incidence. SUA-lowering therapy is a potential strategy for preventing systemic/hepatic metabolic abnormalities.

  17. Dose-response analysis of cadmium-induced tubular proteinuria. A study of urinary. beta. /sub 2/-microglobulin excretion among workers in a battery factory

    Energy Technology Data Exchange (ETDEWEB)

    Kjellstroem, T. (Karolinska Inst. and National Environment Protection Board, Stockholm); Evrin, P.E.; Rahnster, B.

    1977-04-01

    The study covered 240 male and female workers exposed to cadmium oxide and nickel hydroxide dust in a Swedish battery factory. The control group comprised 87 unexposed males. Air samples from the plant showed the present exposure level to be about 50 ..mu..g Cd/m/sup 3/ air. Cadmium-induced effects were studied by measuring urinary ..beta../sub 2/-microglobulin excretion. Urinary ..beta../sub 2/-microglobulin concentration followed a log-normal distribution in the reference group with a geometric mean of 84 ..mu..g/liter (adjusted to a specific gravity of 1.023). In the group of 185 persons continuously exposed to cadmium dust in the work environment, the prevalence of increased urinary ..beta../sub 2/-microglobulin excretion increased with employment time. The prevalence was 19% for the workers with 6-12 years of exposure to about 50 ..mu..g Cd/m/sup 3/ as compared to 3% for those in the reference group. Smokers had about three times higher prevalence than nonsmokers.

  18. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.

    2012-12-01

    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  19. Basic dose response of fluorescent screen-based portal imaging device

    International Nuclear Information System (INIS)

    Yeo, In Hwan; Yonannes, Yonas; Zhu, Yunping

    1999-01-01

    The purpose of this study is to investigate fundamental aspects of the dose response of fluorescent screen-based electronic portal imaging devices (EPIDs). We acquired scanned signal across portal planes as we varied the radiation that entered the EPID by changing the thickness and anatomy of the phantom as well as the air gap between the phantom and the EPID. In addition, we simulated the relative contribution of the scintillation light signal in the EPID system. We have shown that the dose profile across portal planes is a function of the air gap and phantom thickness. We have also found that depending on the density change within the phantom geometry, errors associated with dose response based on the EPID scan can be as high as 7%. We also found that scintillation light scattering within the EPID system is an important source of error. This study revealed and demonstrated fundamental characteristics of dose response of EPID, as relative to that of ion chambers. This study showed that EPID based on fluorescent screen cannot be an accurate dosimetry system

  20. Demonstration of an adaptive response to preconditioning Frankliniella occidentalis (Pergande) to sublethal doses of spinosad: a hormetic-dose response.

    Science.gov (United States)

    Gong, Youhui; Xu, Baoyun; Zhang, Youjun; Gao, Xiwu; Wu, Qingjun

    2015-07-01

    Sublethal doses of some insecticides have been reported to either stimulate or reduce the survival and fecundity of insects. Many sublethal-effect studies have been conducted after exposure of only one generation to sublethal insecticides, and there is little information about the sublethal effects on insects after long-term exposure to sublethal insecticides. In this study, changes in biological characteristics were investigated in spinosad-susceptible (Spin-S) and sublethal-spinosad-treated (Spin-Sub) strains of Frankliniella occidentalis (Pergande) after exposure to their corresponding sublethal concentrations of spinosad. The results showed that for the Spin-S strain, the LC10 concentration of spinosad slightly affected the biotic fitness both in parents and offspring of F. occidentalis. The LC25 concentration of spinosad prolonged the development time, reduced the fecundity, and significantly reduced the intrinsic rate of increase, the net reproductive rate and the finite rate of increase in the Spin-S strain. However, the negative effects were not as pronounced in the offspring (F1 generation) as in the parent generation. For the Spin-Sub strain, the LC10 and LC25 concentrations of spinosad had little negative effect on the development and fecundity, and no significant difference was found between the effects of the LC10 and LC25 treatments on the Spin-Sub strain. The Spin-Sub strain exhibited a shorter developmental time, and larger intrinsic rates of increase and net reproductive rates, compared with the corresponding treatments of the Spin-S strain. These findings combined with our previous studies suggest that the biotic fitness increased in the Spin-Sub strain and the strain became more adaptable to sublethal doses of spinosad, compared with the Spin-S strain. Physiological and biochemical adaptation may contribute to these changes after long treatment times at sublethal doses.

  1. West Nile virus infection in American Robins: new insights on dose response.

    Directory of Open Access Journals (Sweden)

    Kaci K VanDalen

    Full Text Available West Nile virus (WNV is a vector-borne pathogen that was first detected in the United States in 1999. The natural transmission cycle of WNV involves mosquito vectors and avian hosts, which vary in their competency to transmit the virus. American robins are an abundant backyard species in the United States and appear to have an important role in the amplification and dissemination of WNV. In this study we examine the response of American robins to infection with various WNV doses within the range of those administered by some natural mosquito vectors. Thirty American robins were assigned a WNV dosage treatment and needle inoculated with 10(0.95 PFU, 10(1.26 PFU, 10(2.15 PFU, or 10(3.15 PFU. Serum samples were tested for the presence of infectious WNV and/or antibodies, while oral swabs were tested for the presence of WNV RNA. Five of the 30 (17% robins had neutralizing antibodies to WNV prior to the experiment and none developed viremia or shed WNV RNA. The proportion of WNV-seronegative birds that became viremic after WNV inoculation increased in a dose dependent manner. At the lowest dose, only 40% (2/5 of the inoculated birds developed productive infections while at the highest dose, 100% (7/7 of the birds became viremic. Oral shedding of WNV RNA followed a similar trend where robins inoculated with the lower two doses were less likely to shed viral RNA (25% than robins inoculated with one of the higher doses (92%. Viremia titers and morbidity did not increase in a dose dependent manner; only two birds succumbed to infection and, interestingly, both were inoculated with the lowest dose of WNV. It is clear that the disease ecology of WNV is a complex interplay of hosts, vectors, and viral dose delivered.

  2. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  3. Urochloa ruziziensis responses to sources and doses of urea

    Directory of Open Access Journals (Sweden)

    João E. S. Lima

    2016-05-01

    Full Text Available ABSTRACT The use of products that promote reduction of nitrogen (N losses from the urea fertilizer can contribute to increasing its use efficiency in forage grasses. This study aimed to evaluate the effects of N sources and doses on the growth of Urochloa ruziziensis. The experiment was carried out in the growing season of 2007/2008 in Santo Antônio de Goiás-GO, in a Brazilian Oxisol. A completely randomized block was used, with four replicates in a factorial scheme, corresponding to two N sources (conventional urea and urea with urease inhibitor and five N doses (0, 50, 100, 200 and 300 kg ha-1, divided into equal applications in five periods (Nov 14 to Dec 13, Dec 14 to Jan 12, Jan 13 to Feb 11 - rainy season, Mar 24 to Apr 22 and Jul 10 to Aug 08 - dry season. The effects of the treatments were evaluated for: shoot dry matter, tiller density, total N content in the leaves and relative chlorophyll content. N fertilizer sources did not affect the evaluated variables; however, N fertilization allowed linear increases in all variables with higher values during the rainy period. The relative chlorophyll content in U. ruziziensis had positive correlation with its dry matter productivity.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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. (paper)

  5. I-131 dose response for incident thyroid cancers in Ukraine related to the Chornobyl accident.

    Science.gov (United States)

    Brenner, Alina V; Tronko, Mykola D; Hatch, Maureen; Bogdanova, Tetyana I; Oliynik, Valery A; Lubin, Jay H; Zablotska, Lydia B; Tereschenko, Valery P; McConnell, Robert J; Zamotaeva, Galina A; O'Kane, Patrick; Bouville, Andre C; Chaykovskaya, Ludmila V; Greenebaum, Ellen; Paster, Ihor P; Shpak, Victor M; Ron, Elaine

    2011-07-01

    Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers. To address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. The cohort consists of individuals radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose-response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43-6.34], and the EAR per 10⁴ PY/Gy was 2.21 (95% CI, 0.04-5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. I-131-related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.

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

    Science.gov (United States)

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

    2017-12-08

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

  7. 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.

  8. Mechanisms and dose-response relationships for radiation-induced cardiovascular disease.

    Science.gov (United States)

    Stewart, F A

    2012-01-01

    Epidemiological studies have shown a clear association between therapeutic doses of thoracic irradiation and increased risk of cardiovascular disease in long-term cancer survivors. Survivors of Hodgkin's lymphoma and childhood cancers, for example, show 2- to >7-fold increases in risk of cardiac death after total tumour doses of 30-40 Gy, given in 2-Gy fractions. The risk of cardiac mortality increases linearly with dose, although there are large uncertainties for mean cardiac doses heart, this causes progressive loss of capillaries and eventually leads to reduced perfusion, myocardial cell death, and fibrosis. In large arteries, doses of ≥ 8 Gy, combined with elevated cholesterol, initiates atherosclerosis and predisposes to the formation of inflammatory, unstable lesions, which are prone to rupture and may cause a fatal heart attack or stroke. In contrast, doses likely that mechanisms other than accelerated atherosclerosis are responsible for cardiovascular effects after low total-body exposures of radiation (e.g. impaired T-cell immunity or persistent increase in systemic cytokines). Copyright © 2012. Published by Elsevier Ltd.

  9. Dose-time-response association between occupational asbestos exposure and pleural mesothelioma.

    Science.gov (United States)

    Lacourt, Aude; Lévêque, Emilie; Guichard, Elie; Gilg Soit Ilg, Anabelle; Sylvestre, Marie-Pierre; Leffondré, Karen

    2017-09-01

    Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose-response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case-control study. This study included 1196 male cases recruited in 1987-2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure. Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95% CI 2.01 to 2.87)). This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    International Nuclear Information System (INIS)

    Conolly, Rory B.; Gaylor, David W.; Lutz, Werner K.

    2005-01-01

    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

  11. Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

    Science.gov (United States)

    Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

    1989-01-01

    The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

  12. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  13. The dose-response relationships for tumor induction after high-LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Covelli, V.; Coppola, M.; Di Majo, V.; Rebessi, S. (ENEA, Casaccia (Italy). Centro Ricerche Energia)

    1991-12-01

    This paper presents a review of several studies conducted in our laboratory to examine the carcinogenic effects in mice of high-LET radiation, and for comparison of low-LET reference radiation. For some specific end-points the following conclusions can be formulated: (1) the dose-response curves for myeloid leukemia and malignant lymphoma can be interpreted in terms of induction and inactivation; in particular, the data confirmed that a linear depenence of the induction on dose is adequate to describe the response to fission neutrons, while a pure quadratic dependence is consistent with the experimental data for low-LET radiation; (2) in the liver, a marked age-dependence was demonstrated for radiation-induced tumors with a much higher susceptability in young than in old mice; also for these tumors the dose-effect curves can be described by a linear and a quadratic relationships for high- and low-LET radiation, respectively; (3) data on ovarian tumor induction suggested threshold-like dose responses; these peculiar shapes as well as the absence of a clear radiation quality dependence of the curves are difficult findings to explain using a simple model of radiation action, and they might better be related to a non-stochastic effect of hormonal imbalance following irradiation. (author).

  14. Dose response of commercially available optically stimulated luminescent detector, Al2O3:C for megavoltage photons and electrons.

    Science.gov (United States)

    Kim, Dong Wook; Chung, Weon Kuu; Shin, Dong Oh; Yoon, Myonggeun; Hwang, Ui-Jung; Rah, Jeong-Eun; Jeong, Hojin; Lee, Sang Yeob; Shin, Dongho; Lee, Se Byeong; Park, Sung Yong

    2012-04-01

    This study examined the dose response of an optically stimulated luminescence dosemeter (OSLD) to megavoltage photon and electron beams. A nanoDot™ dosemeter was used to measure the dose response of the OSLD. Photons of 6-15 MV and electrons of 9-20 MeV were delivered by a Varian 21iX machine (Varian Medical System, Inc. Milpitas, CA, USA). The energy dependency was dose was linear until 200 cGy. The superficial dose measurements revealed photon irradiation to have an angular dependency. The nanoDot™ dosemeter has potential use as an in vivo dosimetric tool that is independent of the energy, has dose linearity and a rapid response compared with normal in vivo dosimetric tools, such as thermoluminescence detectors. However, the OSLD must be treated very carefully due to the high angular dependency of the photon beam.

  15. Dual effects of phytoestrogens result in u-shaped dose-response curves

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Fernández, Mariana F; Petersen, Jørgen H

    2002-01-01

    , including synthetic chemicals and phytoestrogens, for aromatase inhibition. The phytoestrogens, except genistein, were aromatase inhibitors at low concentrations (resulting in U-shaped dose-response curves. None...

  16. Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees

    International Nuclear Information System (INIS)

    Shata, Mohamed Tarek; Tricoche, Nancy; Perkus, Marion; Tom, Darley; Brotman, Betsy; McCormack, Patricia; Pfahler, Wolfram; Lee, Dong-Hun; Tobler, Leslie H.; Busch, Michael; Prince, Alfred M.

    2003-01-01

    In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion

  17. Georgia fishery study: implications for dose calculations

    International Nuclear Information System (INIS)

    Turcotte, M.D.S.

    1983-01-01

    Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The data indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. A fish consumption value of 11.3 kg/yr should be used to recalculate dose to the average individual from L-Reactor restart. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average fish consumption value of 11.3 kg/yr, and a maximum fish consumption value of 34 kg/yr

  18. Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950-2003.

    Science.gov (United States)

    Schöllnberger, Helmut; Eidemüller, Markus; Cullings, Harry M; Simonetto, Cristoforo; Neff, Frauke; Kaiser, Jan Christian

    2018-03-01

    The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose-response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing 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. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose-response curve from MMI is located below the linear no-threshold model at low and medium doses (0-1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose-response was also found for heart diseases (0-3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose-response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general.

  19. Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder

    Directory of Open Access Journals (Sweden)

    Cardozo Linda

    2010-08-01

    Full Text Available Abstract Background Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI, usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine. Methods Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models. Results The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively. Conclusions A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials. Trial Registration The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723.

  20. Differences in Radiation Dose Response between Small and Large Intestinal Crypts.

    Science.gov (United States)

    Otsuka, Kensuke; Suzuki, Keiji

    2016-09-01

    The protection of intestinal epithelial cells from the lethal effects induced by high-dose radiation is an important issue in radiotherapy and in the treatment of acute radiation syndrome. However, the effects of middle- and low-dose radiation on intestinal epithelial cells remain unclear. Because the accumulation of DNA damage in intestinal stem cells may be crucial for the development of cancer-initiating cells, it is important to understand the kinetics of DNA repair and tissue response (which are involved in the elimination of damaged cells and tissue injury repair) to middle- to low-dose irradiation. In this study, mice were X-ray irradiated with 0.1, 1 or 4 Gy, after which the small intestine (duodenum and ileum) and colon were harvested from the animals. DNA damage repair and the elimination of damaged cells were quantified by measuring the number of foci of 53BP1, a surrogate marker for DNA double-strand breaks. Tissue-proliferative response was evaluated by determining the number of Ki-67(+) and mitotic cells. Intra-crypt response differed considerably between the small intestine and the colon. In the small intestine, 53BP1 foci were detected immediately after irradiation, but rapidly disappeared thereafter, especially noticeable in Lgr5(+) stem cells. Cellular growth was temporally arrested; however, cell numbers and mitotic cell numbers in the crypt did not change. The kinetics of DNA damage repair in Lgr5(+) stem cells were similar to those in the small intestines, while the colon was more susceptible to radiation-induced damage. Preferential cell loss in the lower crypt was clearly observed in the colon; and after low-dose X-ray irradiation, only the colon exhibited considerably reduced cell numbers and dramatic induction of mitosis. These results suggest that differences in radiation dose response between the small and the large intestine may depend on the growth activity of stem cells after DNA repair.

  1. 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 psychosis have not been consistently found. The current study aimed to explore adversity specificity and dose-response effects of adversities on risk of psychosis. METHOD: Participants were 101 persons with first-episode psychosis (FEP) diagnosed with ICD-10 F20 - F29 (except F21) and 101 non......% of the 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 ppsychosis increased two and a half times for each additional adversity. All...

  2. Pre-irradiation at a low dose-rate blunted p53 response

    International Nuclear Information System (INIS)

    Takahashi, A.; Ohnishi, K.; Asakawa, I.; Tamamoto, T.; Yasumoto, J.; Yuki, K.; Ohnishi, T.; Tachibana, A.

    2003-01-01

    Full text: We have studied whether the p53-centered signal transduction pathway induced by acute radiation is interfered with chronic pre-irradiation at a low dose-rate in human cultured cells and whole body of mice. In squamous cell carcinoma cells, we found that a challenge irradiation with X-ray immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge irradiation alone. In addition, the induction of p53-centered apoptosis and the accumulation of its related proteins after the challenge irradiation were strongly correlated with the above-mentioned phenomena. In mouse spleen, the induction of apoptosis and the accumulation of p53 and Bax were observed dose-dependently at 12 h after a challenge irradiation. In contrast, we found significant suppression of them induced by challenge irradiation at a high dose-rate when mice were pre-irradiated with chronic irradiation at a low dose-rate. These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced p53-dependent signal transduction processes. There are numerous papers about p53 functions in apoptosis, radiosensitivity, genomic instability and cancer incidence in cultured cells or animals. According to our data and other findings, since p53 can prevent carcinogenesis, pre-irradiation at a low dose-rate might enhance the predisposition to cancer. Therefore, it is possible that different maximal permissible dose equivalents for the public populations are appropriate. Furthermore, concerning health of human beings, studies of the adaptive responses to radiation are quite important, because the radiation response strongly depends on experience of prior exposure to radiation

  3. Systematic Review and Meta-Analysis: Dose-Response Relationship of Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder.

    Science.gov (United States)

    Jakubovski, Ewgeni; Varigonda, Anjali L; Freemantle, Nicholas; Taylor, Matthew J; Bloch, Michael H

    2016-02-01

    Previous studies suggested that the treatment response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder follows a flat response curve within the therapeutic dose range. The present study was designed to clarify the relationship between dosage and treatment response in major depressive disorder. The authors searched PubMed for randomized placebo-controlled trials examining the efficacy of SSRIs for treating adults with major depressive disorder. Trials were also required to assess improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses. The longitudinal data were analyzed with a mixed-regression model. Endpoint and tolerability analyses were analyzed using meta-regression and stratified subgroup analysis by predefined SSRI dose categories in order to assess the effect of SSRI dosing on the efficacy and tolerability of SSRIs for major depressive disorder. Forty studies involving 10,039 participants were included. Longitudinal modeling (dose-by-time interaction=0.0007, 95% CI=0.0001-0.0013) and endpoint analysis (meta-regression: β=0.00053, 95% CI=0.00018-0.00088, z=2.98) demonstrated a small but statistically significant positive association between SSRI dose and efficacy. Higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects (meta-regression: β=0.00207, 95% CI=0.00071-0.00342, z=2.98) and decreased likelihood of all-cause dropout (meta-regression: β=-0.00093, 95% CI=-0.00165 to -0.00021, z=-2.54). Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses.

  4. Eastern Frequency Response Study

    Energy Technology Data Exchange (ETDEWEB)

    Miller, N.W.; Shao, M.; Pajic, S.; D' Aquila, R.

    2013-05-01

    This study was specifically designed to investigate the frequency response of the Eastern Interconnection that results from large loss-of-generation events of the type targeted by the North American Electric Reliability Corp. Standard BAL-003 Frequency Response and Frequency Bias Setting (NERC 2012a), under possible future system conditions with high levels of wind generation.

  5. Importance of comparative study of CT dose between different centers

    International Nuclear Information System (INIS)

    Ramos Amores, D.; Serna Berna, A.; Mata Colodro, F.; Puchades Puchades, V.

    2013-01-01

    This work aims to show the importance of comparative analysis to get CT study can be made with fewer doses without impeding optimal image quality for diagnosis. With this work we can see that statistical studies on the dose given at two different sites can have beneficial consequences for patients because scanners can work with fewer doses and optimal image quality for diagnosis. (Author)

  6. Response of booster dose of cuban recombinant hepatitis-B vaccine in nonresponder and hyporesponder children

    International Nuclear Information System (INIS)

    Dahifar, H.; Mousavi, F.; Ghorbani, A.

    2007-01-01

    Acute hepatitis B infection can debilitate a patient for weeks and occasionally has a fatal outcome, while chronic infection is a major threat to the individual. To assess response of nonresponder and hyporesponder children to booster dose of Cuban recombinant hepatitis B vaccine. An interventional, descriptive study has been conducted on children who had been immunized with Cuban recombinant Hepatitis B vaccine and their antibody titers were <10mIU/ml (nonresponder) and 10-100mIU/ml (hyporesponder) administered booster dose of the same vaccine in their Deltoid muscles. The response of 141 children with the mean age of 1.9 years to booster dose of vaccine were 94.3% and 100% vaccines with the first and second booster dose of vaccination respectively. The anti-HBs titer in nonresponders and hyporesponders were 468+-346 and 783+-346mIU/ml respectively with significant differences between two groups (P=0.001). This study demonstrate moderately increase antibody production in the majority of vaccines with single supplementary vaccine. (author)

  7. Bayesian nonparametric estimation of continuous monotone functions with applications to dose-response analysis.

    Science.gov (United States)

    Bornkamp, Björn; Ickstadt, Katja

    2009-03-01

    In this article, we consider monotone nonparametric regression in a Bayesian framework. The monotone function is modeled as a mixture of shifted and scaled parametric probability distribution functions, and a general random probability measure is assumed as the prior for the mixing distribution. We investigate the choice of the underlying parametric distribution function and find that the two-sided power distribution function is well suited both from a computational and mathematical point of view. The model is motivated by traditional nonlinear models for dose-response analysis, and provides possibilities to elicitate informative prior distributions on different aspects of the curve. The method is compared with other recent approaches to monotone nonparametric regression in a simulation study and is illustrated on a data set from dose-response analysis.

  8. Dependence of alanine gel dosimeter response as a function of photon clinical beams dose rate

    International Nuclear Information System (INIS)

    Silva, Cleber Feijo; Campos, Leticia Lucente

    2013-01-01

    Gel dosimetry is a new area developed by Gore, it is ery useful for application in radiotherapy because using NMR imaging as evaluation technique is possible to evaluate three dimensional absorbed dose distribution. The measure technique is based on difference of ferrous (Fe 2+ ) and ferric (Fe 3+ ) ) ions concentration that can be measured also by spectrophotometry technique. The Alanine gel dosimeter was developed at IPEN. The alanine is an amino acid and tissue equivalent material that presents significant improvement on previous alanine dosimetry systems. The addition of Alanine increases the production of ferric ions in the solution. This work aims to study the dose rate dependence of photon clinical beams radiation on the alanine gel dosimeter optical response, as well as the response repeatability and gel production reproducibility, since this property is very important for characterization and standardization of any dosimeter. (author)

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

    International Nuclear Information System (INIS)

    Raabe, O.G.

    1987-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Kalita, J.M., E-mail: jitukalita09@gmail.com; Wary, G.

    2016-09-15

    Highlights: • Effect of annealing temperature on TL signal of calcite has been studied. • Specific annealing treatment for optimal dose response has been evaluated. • The dose response of natural calcite has been analyzed quantitatively. - Abstract: The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO{sub 3}) 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.

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  12. The Economic Impact of Levothyroxine Dose Adjustments: the CONTROL HE Study.

    Science.gov (United States)

    Ernst, Frank R; Barr, Peri; Elmor, Riad; Sandulli, Walter; Thevathasan, Lionel; Sterman, Arnold B; Goldenberg, Jessica; Vora, Kevin

    2017-01-01

    In general, hypothyroidism can be adequately treated with a consistent daily dose of levothyroxine. However, the need for levothyroxine dose adjustments is frequent in clinical practice. The extent to which levothyroxine dose adjustments increase the utilization of healthcare resources has not previously been described in the clinical literature. The primary objective of our study was to measure the effect of levothyroxine dose adjustments in terms of their utilization of healthcare resources including direct and indirect costs. A secondary goal was to identify any differences in patient characteristics that may be responsible for levothyroxine dose adjustments. A retrospective medical chart review was conducted among patients of selected healthcare providers in the USA. Patients who were recently started on levothyroxine therapy (levothyroxine dose changes over 24 months: 0 dose changes (no dose adjustment group); one dose change, two dose changes, three or more dose changes (≥1 dose adjustment group). The study included 454 patients. Overall estimated resource utilization was higher per patient in the ≥1 dose adjustment group (US$5824) vs. the no dose adjustment group (US$3166) during the 24-month study period. When direct and indirect costs were combined, overall costs of care were greatest in patients requiring three or more dose adjustments (US$8220/patient). Patients in this cohort incurred 2.5-fold greater total costs compared with patients requiring no dose adjustments (US$8220 vs. US$3166). Among the 58 patients in the group requiring three or more dose adjustments, mean direct medical costs were significantly higher than in the patients requiring no dose adjustments (US$6387 vs. US$2182). Patients with at least one dose adjustment experienced a 40.3% increase in lost productivity vs. patients who had no dose adjustments (US$1381 vs. US$984). Loss of productivity was highest among patients with three or more levothyroxine dose adjustments. Among this

  13. Modelling the dynamic dose response of an nMAG polymer gel dosimeter

    International Nuclear Information System (INIS)

    Ceberg, Sofie; Ceberg, Crister; Lepage, Martin; Bäck, Sven Å J; Gustafsson, Helen

    2012-01-01

    Gel dosimetry measures the absorbed radiation dose with high spatial resolution in 3D. However, recently published data show that the response of metacrylic-based polymer gels depends on the segmented delivery pattern, which could potentially be a considerable disadvantage for measurements of modern dynamic radiotherapy techniques. The aim of this study is to design a dynamic compartment model for the response of a gel dosimeter, exposed to an arbitrary irradiation pattern (segmented delivery and intensity modulation), in order to evaluate the associated effects on absorbed dose measurements. The model is based on the separation of the protons affecting the magnetic resonance signal (i.e. the R2 value) into six compartments, described by a set of differential equations. The model is used to calculate R2 values for a number of different segmented delivery patterns between 0–4 Gy over 1–33 fractions. Very good agreement is found between calculated and measured R2 values, with an average difference of 0.3 ± 1.1% (1 SD). The model is also used to predict the behaviour of a gel dosimeter exposed to irradiation according to typical IMRT, VMAT and respiratory gating scenarios. The calculated R2 values are approximately independent of the segmented delivery, given that the same total dose is delivered during the same total time. It is concluded that this study helps to improve the theoretical understanding of the dependence of metacrylic-based polymer gel response to segmented radiation delivery. (paper)

  14. An apparent threshold dose response in ferrous xylenol-orange gel dosimeters when scanned with a yellow light source

    Science.gov (United States)

    Babic, Steven; Battista, Jerry; Jordan, Kevin

    2008-03-01

    Freshly prepared radiochromic ferrous xylenol-orange (FX) gels optically scanned with a light source exhibit a threshold dose response that is thermally and wavelength dependent. Correction for this threshold dose leads to accurate dose calibration and better reproducibility in multiple fraction radiation exposures. The objective of this study was to determine the cause of the threshold dose effect and to control it through improved dose calibration procedures. The results of a systematic investigation into the chemical cause revealed that impurities within the various FX gel constituents (i.e. xylenol-orange, gelatin, sulfuric acid and ferrous ammonium sulfate) were not directly responsible for the threshold dose. Rather, it was determined that the threshold dose response stems from a spectral sensitivity to different chemical complexes that are formed at different dose levels in FX gels between ferric (Fe(III)) ions and xylenol-orange (XO), i.e. Fe(III)i:XOj. A double Fe(III)2:XO1 complex preferentially absorbs at longer wavelengths (i.e. yellow), while at shorter wavelengths (i.e. green) the sensitivity is biased toward the single Fe(III)1:XO1 complex. As a result, when scanning with yellow light, freshly prepared FX gels require a minimum concentration of Fe(III) ions to shift the equilibrium concentration to favor the predominant production of the double Fe(III)2:XO1 complex at low doses. This can be accomplished via pre-irradiation of freshly prepared gels to a priming dose of ~0.5 Gy or allowing auto-oxidation to generate the startup concentration of Fe(III) ions required to negate the apparent threshold dose response.

  15. Evidence for adaptive response and implication in pulse-simulated low-dose-rate radiotherapy

    International Nuclear Information System (INIS)

    Raaphorst, G.P.; Ng, C.E.; Smith, D.; Niedbala, M.

    2000-01-01

    Purpose: Pulsed-dose-rate (PDR) brachytherapy as a substitute for continuous low-dose-rate (LDR) brachytherapy has a number of clinical advantages. However, early results show that some cells can exhibit an adaptive response to radiation and in PDR where many pulses are given such an adaptive response may play an important role in the outcome. Methods and Materials: Nine human cell lines (two normal fibroblast and seven tumor) were evaluated for an adaptive response. Cells were given either a single adapting dose before a challenge dose or given PDR sequences for which the average dose rate matched the LDR dose rate. Response was assessed using the colony survival assay. Results: Five of the nine cell lines showed an adapting response to single small doses of radiation. Three of these cell lines were further investigated for adapting response to PDR and two of the three lines (one ovarian carcinoma and one glioma) showed an adaptive response which was dependent on pulse size and interval. Conclusion: The data show that an adaptive response can occur in human cells and that it can vary among cell lines. In addition, PDR sequences also produced an adaptive response which could have an affect on PDR therapy if such a response is found in tissues

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

    DEFF Research Database (Denmark)

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

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

  17. The effect of low dose rate on metabolomic response to radiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Goudarzi, Maryam [Georgetown University, Biochemistry and Molecular and Cellular Biology, Washington, DC (United States); Mak, Tytus D. [Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC (United States); Chen, Congju; Smilenov, Lubomir B.; Brenner, David J. [Columbia University, Center for High-Throughput Minimally-Invasive Radiation Biodosimetry, New York, NY (United States); Fornace, Albert J. [Georgetown University, Biochemistry and Molecular and Cellular Biology, Washington, DC (United States); Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC (United States)

    2014-11-15

    Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual's exposure in a radiobiological event and thus would have utility for both triage and injury assessment. (orig.)

  18. Dose-Response Relationship Between Physical Activity and Risk of Heart Failure: A Meta-Analysis.

    Science.gov (United States)

    Pandey, Ambarish; Garg, Sushil; Khunger, Monica; Darden, Douglas; Ayers, Colby; Kumbhani, Dharam J; Mayo, Helen G; de Lemos, James A; Berry, Jarett D

    2015-11-10

    Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose-response association between PA and HF risk has not been reported previously. Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose-response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]-min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67-0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87-0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77-0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58-0.73) the minimum guideline-recommended levels. There is an inverse dose-response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk. © 2015 American Heart Association, Inc.

  19. Clinical application of Chamomilla recutita in phlebitis: dose response curve study Aplicación clínica de la Chamomilla recutita en flebitis: estudio de la curva dosis-respuesta Aplicação clínica da Chamomilla recutita em flebites: estudo de curva dose-resposta

    Directory of Open Access Journals (Sweden)

    Paula Elaine Diniz dos Reis

    2011-02-01

    Full Text Available This experimental and dose-response curve study aimed to carry out the quality control of the Chamomilla recutita sample, as well as to estimate the ideal dose, for anti-inflammatory effect, of the extract of its capitula, in patients with phlebitis due to peripheral intravenous infusion of antineoplastic chemotherapy and to evaluate the toxicity of this extract in human beings. The therapeutic efficacy, concerning the anti-inflammatory potential, of different doses of Chamomilla recutita extract were analyzed and compared in 25 patients. The time of regression of phlebitis was shorter for groups with 2.5% concentration (mean=29.2h, standard deviation = 8.98 and 5% concentration (mean = 38.8h, standard deviation = 17.47. Local toxicity was almost not observed. This research contributes to the innovation of the nursing clinical practice, since it suggests an alternative for the treatment of phlebitis through the clinical use of phytotherapeutic drugs.En este estudio, se buscó realizar el control de calidad de la muestra de Chamomilla recutita, así como estimar la dosis ideal, para efecto antiinflamatorio, de la infusión de sus inflorescencias, en pacientes con flebitis proveniente de introducción intravenosa periférica de quimioterapia antineoplásica y evaluar la toxicidad de esta infusión en los seres humanos. Se trata de estudio experimental, del tipo curva dosis-respuesta, en el cual fue analizada y comparada la eficacia terapéutica, en cuanto al potencial antiinflamatorio, de diferentes dosis de la infusión de la Chamomilla recutita en 25 pacientes. El tiempo de regresión de la flebitis fue menor para los grupos con concentración 2,5% (promedio = 29,2h, desviación estándar = 8,98 y 5% (promedio = 38,8h, desviación estándar = 17,47 y prácticamente no se observó toxicidad local. Esta investigación contribuye para la innovación de la práctica clínica en enfermería, una vez que sugiere una alternativa para el tratamiento de

  20. Influences of mechanical exposure biographies on physical capabilities of workers from automotive industry - a study on possible dose-response relationships and consequences for short and long term job rotation.

    Science.gov (United States)

    Rademacher, Holger; Bruder, Ralph; Sinn-Behrendt, Andrea; Landau, Kurt

    2012-01-01

    This paper describes a field study in production areas of a vehicle manufacturing plant, where 106 male workers (aged from 20 to 63 years) were examined and interviewed by the authors. Aim of study was to identify relationships between specific physical worker capabilities and doses of mechanical exposures using self-developed standardized questionnaires as well as a battery of work-specific tests. The dependent variables are different "physical capabilities", classified using a five-point rating scale with regard to the grade of limitation of the respective capability. Independent variables are "age" and specific "mechanical exposures". Several exposures were combined and multiplied with their respective durations in order to determine doses on three different body regions - back, shoulder-neck and upper limbs. There are significant positive correlations between "age" and "dose of mechanical exposure on back/shoulder-neck/upper limbs region". The analysis of the relationship between dose of exposure and different capabilities to lift or reposition loads (with variable weight) shows weak significant correlations for all three body regions. Data analysis shows no significant correlations between any dose of mechanical exposure and capabilities to work in awkward body postures.These results should be considered in age management programs when scheduling future employee assignments to workplaces, especially for production systems where manual handling tasks are dominant.

  1. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013.

    Science.gov (United States)

    Kyu, Hmwe H; Bachman, Victoria F; Alexander, Lily T; Mumford, John Everett; Afshin, Ashkan; Estep, Kara; Veerman, J Lennert; Delwiche, Kristen; Iannarone, Marissa L; Moyer, Madeline L; Cercy, Kelly; Vos, Theo; Murray, Christopher J L; Forouzanfar, Mohammad H

    2016-08-09

     To quantify the dose-response associations between total physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events.  Systematic review and Bayesian dose-response meta-analysis.  PubMed and Embase from 1980 to 27 February 2016, and references from relevant systematic reviews. Data from the Study on Global AGEing and Adult Health conducted in China, Ghana, India, Mexico, Russia, and South Africa from 2007 to 2010 and the US National Health and Nutrition Examination Surveys from 1999 to 2011 were used to map domain specific physical activity (reported in included studies) to total activity.  Prospective cohort studies examining the associations between physical activity (any domain) and at least one of the five diseases studied.  174 articles were identified: 35 for breast cancer, 19 for colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic stroke (some articles included multiple outcomes). Although higher levels of total physical activity were significantly associated with lower risk for all outcomes, major gains occurred at lower levels of activity (up to 3000-4000 metabolic equivalent (MET) minutes/week). For example, individuals with a total activity level of 600 MET minutes/week (the minimum recommended level) had a 2% lower risk of diabetes compared with those reporting no physical activity. An increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%. The same amount of increase yielded much smaller returns at higher levels of activity: an increase of total activity from 9000 to 12 000 MET minutes/week reduced the risk of diabetes by only 0.6%. Compared with insufficiently active individuals (total activity active category (≥8000 MET minutes/week) was 14% (relative risk 0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789, 0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25% (0.754, 0

  2. Accumulated Delivered Dose Response of Stereotactic Body Radiation Therapy for Liver Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Swaminath, Anand [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Massey, Christine [Department of Medical Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brierley, James D.; Dinniwell, Rob; Wong, Rebecca; Kim, John J. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Velec, Michael [Department of Radiation Therapy, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brock, Kristy K. [Department of Medical Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2015-11-01

    Purpose: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases. Methods and Materials: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board–approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm{sup 3} (minPTV) was recorded. The accumulated minimum dose to the 0.5 cm{sup 3} gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping. Results: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the acc

  3. Assessing the uncertainty in QUANTEC's dose-response relation of lung and spinal cord with a bootstrap analysis.

    Science.gov (United States)

    Wedenberg, Minna

    2013-11-15

    To apply a statistical bootstrap analysis to assess the uncertainty in the dose-response relation for the endpoints pneumonitis and myelopathy reported in the QUANTEC review. The bootstrap method assesses the uncertainty of the estimated population-based dose-response relation due to sample variability, which reflects the uncertainty due to limited numbers of patients in the studies. A large number of bootstrap replicates of the original incidence data were produced by random sampling with replacement. The analysis requires only the dose, the number of patients, and the number of occurrences of the studied endpoint, for each study. Two dose-response models, a Poisson-based model and the Lyman model, were fitted to each bootstrap replicate using maximum likelihood. The bootstrap analysis generates a family of curves representing the range of plausible dose-response relations, and the 95% bootstrap confidence intervals give an estimated upper and lower toxicity risk. The curve families for the 2 dose-response models overlap for doses included in the studies at hand but diverge beyond that, with the Lyman model suggesting a steeper slope. The resulting distributions of the model parameters indicate correlation and non-Gaussian distribution. For both data sets, the likelihood of the observed data was higher for the Lyman model in >90% of the bootstrap replicates. The bootstrap method provides a statistical analysis of the uncertainty in the estimated dose-response relation for myelopathy and pneumonitis. It suggests likely values of model parameter values, their confidence intervals, and how they interrelate for each model. Finally, it can be used to evaluate to what extent data supports one model over another. For both data sets considered here, the Lyman model was preferred over the Poisson-based model. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Response of MOSFETs from DMILL technology to high total doses; Comportement de la technologie CMOS DMILL aux fortes doses cumulees

    Energy Technology Data Exchange (ETDEWEB)

    Armani, J.M.; Brisset, C.; Joffre, F. [CEA Saclay, Dept. d' Electronique et d' Instrumentation Nucleaire, LETI, 91 - Gif-sur-Yvette (France); Dentan, M. [CEA Saclay, Dept. d' Astrophysique, de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, 91 - Gif sur Yvette (France)

    1999-07-01

    We have studied the behaviour of MOS transistors with DMILL technology submitted to {sup 60}Co gamma radiation. The cumulated dose was 1 MGy(Si) with a dose rate of 1 kGy(Si). The shift of the threshold voltage for an integrated dose beyond 1 MGy(Si) was less than 0.87 V even in the worst case. The analysis of the results shows that the effects of the traps located at the interface Si-SiO{sub 2} become predominant for doses just over a few hundreds kilo-Gray. The weak shift observed enables DMILL-MOS transistors to be validated in civil nuclear applications where cumulated doses may be high. (A.C.)

  5. Dose reduction and optimization studies (ALARA) at nuclear power facilities

    International Nuclear Information System (INIS)

    Baum, J.W.; Meinhold, C.B.

    1983-01-01

    Brookhaven National Laboratory (BNL) has been commissioned by the Nuclear Regulatory Commission (NRC) to study dose-reduction techniques and effectiveness of as low as reasonably achievable (ALARA) planning at LWR plants. These studies have the following objectives: identify high-dose maintenance tasks; identify dose-reduction techniques; examine incentives for dose reduction; evaluate cost-effectiveness and optimization of dose-reduction techniques; and compile an ALARA handbook on data, engineering modifications, cost-effectiveness calculations, and other information of interest to ALARA practioners

  6. Cellular Response to Exponentially Increasing and Decreasing Dose Rates: Implications for Treatment Planning in Targeted Radionuclide Therapy.

    Science.gov (United States)

    Solanki, Jay H; Tritt, Thomas; Pasternack, Jordan B; Kim, Julia J; Leung, Calvin N; Domogauer, Jason D; Colangelo, Nicholas W; Narra, Venkat R; Howell, Roger W

    2017-08-01

    The treatment of cancer using targeted radionuclide therapy is of interest to nuclear medicine and radiation oncology because of its potential for killing tumor cells while minimizing dose-limiting toxicities to normal tissue. The ionizing radiations emitted by radiopharmaceuticals deliver radiation absorbed doses over protracted periods of time with continuously varying dose rates. As targeted radionuclide therapy becomes a more prominent part of cancer therapy, accurate models for estimating the biologically effective dose (BED) or equieffective dose (EQD2 α/β ) will become essential for treatment planning. This study examines the radiobiological impact of the dose rate increase half-time during the uptake phase of the radiopharmaceutical. MDA-MB-231 human breast cancer cells and V79 Chinese hamster lung fibroblasts were irradiated chronically with 662 keV γ rays delivered with time-varying dose rates that are clinically relevant. The temporal dose-rate patterns were: 1. acute, 2. exponential decrease with a half-time of 64 h (T d = 64 h), 3. initial exponential increase to a maximum (half time T i = 2, 8 or 24 h) followed by exponential decrease (T d = 64 h). Cell survival assays were conducted and surviving fractions were determined. There was a marked reduction in biological effect when T i was increased. Cell survival data were tested against existing dose-response models to assess their capacity to predict response. Currently accepted models that are used in radiation oncology overestimated BED and EQD2 α/β at low-dose rates and underestimated them at high-dose rates. This appears to be caused by an adaptive response arising as a consequence of the initial low-dose-rate phase of exposure. An adaptive response function was derived that yields more accurate BED and EQD2 α/β values over the spectrum of dose rates and absorbed doses delivered. Our experimental data demonstrate a marked increase in cell survival when the dose-rate-increase half-time is

  7. Dose-response relationship of autonomic nervous system responses to individualized training impulse in marathon runners.

    Science.gov (United States)

    Manzi, Vincenzo; Castagna, Carlo; Padua, Elvira; Lombardo, Mauro; D'Ottavio, Stefano; Massaro, Michele; Volterrani, Maurizio; Iellamo, Ferdinando

    2009-06-01

    In athletes, exercise training induces autonomic nervous system (ANS) adaptations that could be used to monitor training status. However, the relationship between training and ANS in athletes has been investigated without regard for individual training loads. We tested the hypothesis that in long-distance athletes, changes in ANS parameters are dose-response related to individual volume/intensity training load and could predict athletic performance. A spectral analysis of heart rate (HR), systolic arterial pressure variability, and baroreflex sensitivity by the sequences technique was investigated in eight recreational athletes during a 6-mo training period culminating with a marathon. Individualized training load responses were monitored by a modified training impulse (TRIMP(i)) method, which was determined in each athlete using the individual HR and lactate profiling determined during a treadmill test. Monthly TRIMP(i) steadily increased during the training period. All the ANS parameters were significantly and very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.90 to 0.99; P baroreflex sensitivity resembled a bell-shaped curve with a minimum at the highest TRIMP(i), whereas low-frequency oscillations of HR and systolic arterial pressure variability and the low frequency (LF)-to-high frequency ratio resembled an U-shaped curve with a maximum at the highest TRIMP(i). The LF component of HRV assessed at the last recording session was significantly and inversely correlated to the time needed to complete the nearing marathon. These results suggest that in recreational athletes, ANS adaptations to exercise training are dose related on an individual basis, showing a progressive shift toward a sympathetic predominance, and that LF oscillations in HRV at peak training load could predict athletic achievement in this athlete population.

  8. Low-dose dose-response for reduced cell viability after exposure of human keratinocyte (HEK001 cells to arsenite

    Directory of Open Access Journals (Sweden)

    Kenneth T. Bogen

    Full Text Available The in vitro arsenite (AsIII cytotoxicity dose-response (DR of human keratinocytes (HEK001 was examined at greater statistical resolution than ever previously reported using the MTT assay to determine cell viability. Fifty-four 96-well plates were treated with AsIII concentrations of 0.25, 0.5, 1, 2, 3, 4, 5, 7, 10, 15, 20, 25, or 30 μM. Because of unexpected variation in viability response patterns, a two-stage DR analysis was used in which data on plate-specific viability (%, estimated as 100% times the ratio of measured viability in exposed to unexposed cells, were fit initially to a generalized lognormal response function positing that HEK001 cells studied consisted of: a proportion P of relatively highly sensitive (HS cells, a proportion Po of relatively resistant cells, and a remaining (1–P–Po fraction of typical-sensitivity (TS cells exhibiting the intermediate level of AsIII sensitivity characteristic of most cells in each assay. The estimated fractions P and Po were used to adjust data from all 54 plates (and from the 28 plates yielding the best fits to reflect the condition that P = Po = 0 to provide detailed DR analysis specifically for TS cells. Four DR models fit to the combined adjusted data were each very predictive (R2 > 0.97 overall but were inconsistent with at least one of the data set examined (p  0.30 and exceeded 100% significance (p ≤ 10−6. A low-dose hormetic model provided the best fit to the combined adjusted data for TS cells (R2 = 0.995. Marked variability in estimates of P (the proportion of apparent HS cells was unexpected, not readily explained, and warrants further study using additional cell lines and assay methods, and in vivo. Keywords: Arsenic, Arsenate, Cell culture, Cell death, Cytotoxicity, HEK001 cells

  9. Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

    Science.gov (United States)

    Taylor, Olivia; Van Laeken, Nick; Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

    2017-01-01

    Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

  10. Dose-response relationship between hand-transmitted vibration and hand-arm vibration syndrome in a tropical environment.

    Science.gov (United States)

    Su, Anselm Ting; Maeda, Setsuo; Fukumoto, Jin; Darus, Azlan; Hoe, Victor C W; Miyai, Nobuyuki; Isahak, Marzuki; Takemura, Shigeki; Bulgiba, Awang; Yoshimasu, Kouichi; Miyashita, Kazuhisa

    2013-07-01

    The dose-response relationship for hand-transmitted vibration has been investigated extensively in temperate environments. Since the clinical features of hand-arm vibration syndrome (HAVS) differ between the temperate and tropical environment, we conducted this study to investigate the dose-response relationship of HAVS in a tropical environment. A total of 173 male construction, forestry and automobile manufacturing plant workers in Malaysia were recruited into this study between August 2011 and 2012. The participants were interviewed for history of vibration exposure and HAVS symptoms, followed by hand functions evaluation and vibration measurement. Three types of vibration doses-lifetime vibration dose (LVD), total operating time (TOT) and cumulative exposure index (CEI)-were calculated and its log values were regressed against the symptoms of HAVS. The correlation between each vibration exposure dose and the hand function evaluation results was obtained. The adjusted prevalence ratio for finger tingling and numbness was 3.34 (95% CI 1.27 to 8.98) for subjects with lnLVD≥20 ln m(2) s(-4) against those <16 ln m(2) s(-4). Similar dose-response pattern was found for CEI but not for TOT. No subject reported white finger. The prevalence of finger coldness did not increase with any of the vibration doses. Vibrotactile perception thresholds correlated moderately with lnLVD and lnCEI. The dose-response relationship of HAVS in a tropical environment is valid for finger tingling and numbness. The LVD and CEI are more useful than TOT when evaluating the dose-response pattern of a heterogeneous group of vibratory tools workers.

  11. Overweight, obesity and risk of all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus: a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Liu, Xue-ming; Liu, Yu-jian; Zhan, Jian; He, Qi-qiang

    2015-01-01

    Overweight and obese individuals with type 2 diabetes are recommended to lose weight, but the associations between excess body weight and all-cause and cardiovascular mortality in patients with type 2 diabetes remain controversial. Therefore, we performed a dose-response meta-analysis to investigate this association. We searched PubMed and Embase through 19th October 2014 and examined the references of retrieved articles to identify relevant prospective cohort studies. A random-effect model was used to calculate the summary risk estimates. Nine studies including 13 cohorts with 161,984 participants were identified. The relative risks (RRs) of all-cause mortality in overweight and obese patients with type 2 diabetes were 0.81 (95% confidence interval (CI) 0.74-0.90) and 0.72 (95% CI 0.63-0.81) respectively, compared with the normal or non-overweight patients. Furthermore, a 5 kg/m(2) increase in body mass index was associated with a significantly reduced risk of all-cause mortality by 5% (RR 0.95, 95% CI 0.93-0.97). However, no significant association was found between obese and/or overweight and the risk of cardiovascular mortality in type 2 diabetic patients (RR 0.89; 95% CI 0.66-1.20 for overweight and RR 0.77; 95% CI 0.54-1.10 for obesity, respectively). The findings from the present meta-analysis indicate that excess body weight may be a protective factor for all-cause mortality among patients with type 2 diabetes.

  12. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies

    OpenAIRE

    Vally, H; Thompson, P

    2001-01-01

    BACKGROUND—Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose su...

  13. Radiation dose to the patient in radionuclide studies

    International Nuclear Information System (INIS)

    Roedler, H.D.

    1981-01-01

    In medical radionuclide studies, the radiation risk has to be considered in addition to the general risk of administering a pharmaceutical. As radiation exposure is an essential factor in radiation risk estimation, some aspects of internal dose calculation, including radiation risk assessments, are treated. The formalism of current internal dose calculation is presented. The input data, especially the residence time and the absorbed dose per transformation, their origin and accuracy are discussed. Results of internal dose calculations for the ten most frequently used radionuclide studies are presented as somatically effective dose equivalents. The accuracy of internal dose calculation is treated in detail by considering the biokinetics of the radiopharmaceutical, the phantoms used for dose calculations, the absorbed dose per transformation, the administered activity, and the transfer of the dose, calculated for a phantom, to the patient. The internal dose calculated for a reference phantom may be assumed to be in accordance with the actual patient dose within a range described by a factor of about two to three. Finally, risk estimates for nuclear medicine procedures are quantified, being generally of sixth order. The radiation risk from the radioiodine test is comparably higher, but probably lower than calculated according to the UNSCEAR risk coefficients. However, further studies are needed to confirm these preliminary results and to improve the quantification of the radiation risk from the medical use of radionuclides. (author)

  14. A novel method of estimating dose responses for polymer gels using texture analysis of scanning electron microscopy images.

    Directory of Open Access Journals (Sweden)

    Cheng-Ting Shih

    Full Text Available Polymer gels are regarded as a potential dosimeter for independent validation of absorbed doses in clinical radiotherapy. Several imaging modalities have been used to convert radiation-induced polymerization to absorbed doses from a macro-scale viewpoint. This study developed a novel dose conversion mechanism by texture analysis of scanning electron microscopy (SEM images. The modified N-isopropyl-acrylamide (NIPAM gels were prepared under normoxic conditions, and were administered radiation doses from 5 to 20 Gy. After freeze drying, the gel samples were sliced for SEM scanning with 50×, 500×, and 3500× magnifications. Four texture indices were calculated based on the gray level co-occurrence matrix (GLCM. The results showed that entropy and homogeneity were more suitable than contrast and energy as dose indices for higher linearity and sensitivity of the dose response curves. After parameter optimization, an R (2 value of 0.993 can be achieved for homogeneity using 500× magnified SEM images with 27 pixel offsets and no outlier exclusion. For dose verification, the percentage errors between the prescribed dose and the measured dose for 5, 10, 15, and 20 Gy were -7.60%, 5.80%, 2.53%, and -0.95%, respectively. We conclude that texture analysis can be applied to the SEM images of gel dosimeters to accurately convert micro-scale structural features to absorbed doses. The proposed method may extend the feasibility of applying gel dosimeters in the fields of diagnostic radiology and radiation protection.

  15. Validation of dose-response calibration curve for X-Ray field of CRCN-NE/CNEN: preliminary results

    International Nuclear Information System (INIS)

    Silva, Laís Melo; Mendonç, Julyanne Conceição de Goes; Andrade, Aida Mayra Guedes de; Hwang, Suy F.; Mendes, Mariana Esposito; Lima, Fabiana F.; Melo, Ana Maria M.A.

    2017-01-01

    It is very important in accident investigations that accurate estimating of absorbed dose takes place, so that it contributes to medical decisions and overall assessment of long-term health consequences. Analysis of chromosome aberrations is the most developed method for biological monitoring, and frequencies of dicentric chromosomes are related to absorbed dose of human peripheral blood lymphocytes using calibration curves. International Atomic Energy Agency (IAEA) recommends that each biodosimetry laboratory sets its own calibration curves, given that there are intrinsic differences in protocols and dose interpretations when using calibration curves produced in other laboratories, which could add further uncertainties to dose estimations. The Laboratory for Biological Dosimetry CRCN-NE recently completed dose-response calibration curves for X ray field. Curves of chromosomes dicentrics and dicentrics plus rings were made using Dose Estimate. This study aimed to validate the calibration curves dose-response for X ray with three irradiated samples. Blood was obtained by venipuncture from healthy volunteer and three samples were irradiated by x-rays of 250 kVp with different absorbed doses (0,5Gy, 1Gy and 2Gy). The irradiation was performed at the CRCN-NE/CNEN Metrology Service with PANTAK X-ray equipment, model HF 320. The frequency of dicentric and centric rings chromosomes were determined in 500 metaphases per sample after cultivation of lymphocytes, and staining with Giemsa 5%. Results showed that the estimated absorbed doses are included in the confidence interval of 95% of real absorbed dose. These Dose-response calibration curves (dicentrics and dicentrics plus rings) seems valid, therefore other tests will be done with different volunteers. (author)

  16. Validation of dose-response calibration curve for X-Ray field of CRCN-NE/CNEN: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Laís Melo; Mendonç, Julyanne Conceição de Goes; Andrade, Aida Mayra Guedes de; Hwang, Suy F.; Mendes, Mariana Esposito; Lima, Fabiana F., E-mail: falima@cnen.gov.br, E-mail: mendes_sb@hotmail.com [Centro Regional de Ciências Nucleares, (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Melo, Ana Maria M.A., E-mail: july_cgm@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Vitória de Santo Antão, PE (Brazil). Centro Acadêmico de Vitória

    2017-07-01

    It is very important in accident investigations that accurate estimating of absorbed dose takes place, so that it contributes to medical decisions and overall assessment of long-term health consequences. Analysis of chromosome aberrations is the most developed method for biological monitoring, and frequencies of dicentric chromosomes are related to absorbed dose of human peripheral blood lymphocytes using calibration curves. International Atomic Energy Agency (IAEA) recommends that each biodosimetry laboratory sets its own calibration curves, given that there are intrinsic differences in protocols and dose interpretations when using calibration curves produced in other laboratories, which could add further uncertainties to dose estimations. The Laboratory for Biological Dosimetry CRCN-NE recently completed dose-response calibration curves for X ray field. Curves of chromosomes dicentrics and dicentrics plus rings were made using Dose Estimate. This study aimed to validate the calibration curves dose-response for X ray with three irradiated samples. Blood was obtained by venipuncture from healthy volunteer and three samples were irradiated by x-rays of 250 kVp with different absorbed doses (0,5Gy, 1Gy and 2Gy). The irradiation was performed at the CRCN-NE/CNEN Metrology Service with PANTAK X-ray equipment, model HF 320. The frequency of dicentric and centric rings chromosomes were determined in 500 metaphases per sample after cultivation of lymphocytes, and staining with Giemsa 5%. Results showed that the estimated absorbed doses are included in the confidence interval of 95% of real absorbed dose. These Dose-response calibration curves (dicentrics and dicentrics plus rings) seems valid, therefore other tests will be done with different volunteers. (author)

  17. Alanine aminotransferase and risk of the metabolic syndrome: a linear dose-response relationship.

    Directory of Open Access Journals (Sweden)

    Setor K Kunutsor

    Full Text Available BACKGROUND: Elevated baseline circulating alanine aminotransferase (ALT level has been demonstrated to be associated with an increased risk of the metabolic syndrome (MetS, but the nature of the dose-response relationship is uncertain. METHODS: We performed a systematic review and meta-analysis of published prospective cohort studies to characterize in detail the nature of the dose-response relationship between baseline ALT level and risk of incident MetS in the general population. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Prospective studies in which investigators reported relative risks (RRs of MetS for 3 or more categories of ALT levels were eligible. A potential nonlinear relationship between ALT levels and MetS was examined using restricted cubic splines. RESULTS: Of the 489 studies reviewed, relevant data were available on 29,815 non-overlapping participants comprising 2,125 incident MetS events from five prospective cohort studies. There was evidence of a linear association (P for nonlinearity=0.38 between ALT level and risk of MetS, characterised by a graded increase in MetS risk at ALT levels 6-40 U/L. The risk of MetS increased by 14% for every 5 U/L increment in circulating ALT level (95% CI: 12-17%. Evidence was lacking of heterogeneity and publication bias among the contributing studies. CONCLUSIONS: Baseline ALT level is associated with risk of the MetS in a linear dose-response manner. Studies are needed to determine whether the association represents a causal relationship.

  18. 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.

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

    International Nuclear Information System (INIS)

    Calabrese, Edward J.

    2005-01-01

    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. 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

    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 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 including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly...

  1. Response surfaces and sensitivity analyses for an environmental model of dose calculations

    International Nuclear Information System (INIS)

    Iooss, Bertrand; Van Dorpe, Francois; Devictor, Nicolas

    2006-01-01

    A parametric sensitivity analysis is carried out on GASCON, a radiological impact software describing the radionuclides transfer to the man following a chronic gas release of a nuclear facility. An effective dose received by age group can thus be calculated according to a specific radionuclide and to the duration of the release. In this study, we are concerned by 18 output variables, each depending of approximately 50 uncertain input parameters. First, the generation of 1000 Monte-Carlo simulations allows us to calculate correlation coefficients between input parameters and output variables, which give a first overview of important factors. Response surfaces are then constructed in polynomial form, and used to predict system responses at reduced computation time cost; this response surface will be very useful for global sensitivity analysis where thousands of runs are required. Using the response surfaces, we calculate the total sensitivity indices of Sobol by the Monte-Carlo method. We demonstrate the application of this method to one site of study and to one reference group near the nuclear research Center of Cadarache (France), for two radionuclides: iodine 129 and uranium 238. It is thus shown that the most influential parameters are all related to the food chain of the goat's milk, in decreasing order of importance: dose coefficient 'effective ingestion', goat's milk ration of the individuals of the reference group, grass ration of the goat, dry deposition velocity and transfer factor to the goat's milk

  2. Dose response and post-irradiation characteristics of the Sunna 535-nm photo-fluorescent film dosimeter

    International Nuclear Information System (INIS)

    Murphy, M.K.; Kovacs, A.; Miller, S.D.; McLaughlin, W.L.

    2003-01-01

    Results of characterization studies on one of the first versions of the Sunna photo-fluorescent dosimeter TM have previously been reported, and the performance of the red fluorescence component described. This present paper describes dose response and post-irradiation characteristics of the green fluorescence component from the same dosimeter film (Sunna Model γ), which is manufactured using the injection molding technique. This production method may supply batch sizes on the order of 1 million dosimeter film elements while maintaining a signal precision (1σ) on the order of ±1% without the need to correct for variability of film thickness. The dosimeter is a 1 cmx3 cm polymeric film of 0.5-mm thickness that emits green fluorescence at intensities increasing almost linearly with dose. The data presented include dose response, post-irradiation growth, heat treatment, dosimeter aging, dose rate dependence, energy dependence, dose fractionation, variation of response within a batch, and the stability of the fluorimeter response. The results indicate that, as a routine dosimeter, the green signal provides a broad range of response at food irradiation (0.3-5 kGy), medical sterilization (5-40 kGy), and polymer cross-linking (40-250 kGy) dose levels

  3. Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose.

    Science.gov (United States)

    Kör, Deniz; Yılmaz, Berna Şeker; Bulut, Fatma Derya; Ceylaner, Serdar; Mungan, Neslihan Önenli

    2017-07-26

    Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.

  4. 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

  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 analysis of parotid gland function: what is the best measure of xerostomia?

    Science.gov (United States)

    Miah, Aisha B; Gulliford, Sarah L; Clark, Catharine H; Bhide, Shreerang A; Zaidi, Shane H; Newbold, Kate L; Harrington, Kevin J; Nutting, Christopher M

    2013-03-01

    To describe the dose-response relationships for the different measures of salivary gland recovery following radical radiotherapy for locally advanced head and neck squamous cell cancers (LA-HNSCC). Dosimetric analysis of data from the PARSPORT trial, a Phase III study of conventional RT (RT) and intensity modulated radiotherapy (IMRT) for LA-HNSCC was undertaken to determine the relationship between parotid gland mean dose and toxicity endpoints: high-grade subjective and objective xerostomia and xerostomia-related quality of life scores. LKB-NTCP parameters (TD50, m and n) were generated and tolerance doses (D50) reported using non-linear logistic regression analysis. Data were available on 63 patients from the PARSPORT trial. Parotid saliva flow rate provided the strongest association between mean dose and recovery, D50=23.4 Gy (20.6-26.2) and k=3.2 (1.9-4.5), R(2)=0.85. Corresponding LKB parameters were TD50=26.3 Gy (95% CI: 24.0-30.1), m=0.25 (0.18-1.0 and n=1). LENTSOMA subjective xerostomia also demonstrated a strong association D50=33.3 Gy (26.7-39.8), k=2.8 (91.4-4.4), R(2)=0.77). We recommend using the LENT SOMA subjective xerostomia score to predict recovery of salivation due to its strong association with dosimetry and ease of recording. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Dose/volume–response relations for rectal morbidity using planned and simulated motion-inclusive dose distributions

    International Nuclear Information System (INIS)

    Thor, Maria; Apte, Aditya; Deasy, Joseph O.; Karlsdóttir, Àsa; Moiseenko, Vitali; Liu, Mitchell; Muren, Ludvig Paul

    2013-01-01

    Background and purpose: Many dose-limiting normal tissues in radiotherapy (RT) display considerable internal motion between fractions over a course of treatment, potentially reducing the appropriateness of using planned dose distributions to predict morbidity. Accounting explicitly for rectal motion could improve the predictive power of modelling rectal morbidity. To test this, we simulated the effect of motion in two cohorts. Materials and methods: The included patients (232 and 159 cases) received RT for prostate cancer to 70 and 74 Gy. Motion-inclusive dose distributions were introduced as simulations of random or systematic motion to the planned dose distributions. Six rectal morbidity endpoints were analysed. A probit model using the QUANTEC recommended parameters was also applied to the cohorts. Results: The differences in associations using the planned over the motion-inclusive dose distributions were modest. Statistically significant associations were obtained with four of the endpoints, mainly at high doses (55–70 Gy), using both the planned and the motion-inclusive dose distributions, primarily when simulating random motion. The strongest associations were observed for GI toxicity and rectal bleeding (Rs = 0.12–0.21; Rs = 0.11–0.20). Applying the probit model, significant associations were found for tenesmus and rectal bleeding (Rs = 0.13, p = 0.02). Conclusion: Equally strong associations with rectal morbidity were observed at high doses (>55 Gy), for the planned and the simulated dose distributions including in particular random rectal motion. Future studies should explore patient-specific descriptions of rectal motion to achieve improved predictive power

  8. 3D calculation of absorbed dose for 131I-targeted radiotherapy: A Monte Carlo study

    International Nuclear Information System (INIS)

    Saeedzadeh, E.; Sarkar, S.; Abbaspour Tehrani-Fard, A.; Ay, M. R.; Khosravi, H. R.; Loudos, G.

    2008-01-01

    Various methods, such as those developed by the Medical Internal Radiation Dosimetry (MIRD) Committee of the Society of Nuclear Medicine or employing dose point kernels, have been applied to the radiation dosimetry of 131 I radionuclide therapy. However, studies have not shown a strong relationship between tumour absorbed dose and its overall therapeutic response, probably due in part to inaccuracies in activity and dose estimation. In the current study, the GATE Monte Carlo computer code was used to facilitate voxel-level radiation dosimetry for organ activities measured in an. 131 I-treated thyroid cancer patient. This approach allows incorporation of the size, shape and composition of organs (in the current study, in the Zubal anthropomorphic phantom) and intra-organ and intra-tumour inhomogeneities in the activity distributions. The total activities of the tumours and their heterogeneous distributions were measured from the SPECT images to calculate the dose maps. For investigating the effect of activity distribution on dose distribution, a hypothetical homogeneous distribution of the same total activity was considered in the tumours. It was observed that the tumour mean absorbed dose rates per unit cumulated activity were 0.65 E-5 and 0.61 E-5 mGY MBq -1 s -1 for the uniform and non-uniform distributions in the tumour, respectively, which do not differ considerably. However, the dose-volume histograms (DVH) show that the tumour non-uniform activity distribution decreases the absorbed dose to portions of the tumour volume. In such a case, it can be misleading to quote the mean or maximum absorbed dose, because overall response is likely limited by the tumour volume that receives low (i.e. non-cytocidal) doses. Three-dimensional radiation dosimetry, and calculation of tumour DVHs, may lead to the derivation of clinically reliable dose-response relationships and therefore may ultimately improve treatment planning as well as response assessment for radionuclide

  9. X-ray conditions and response characteristics of automatic dose control in cinematography

    International Nuclear Information System (INIS)

    Arai, Hiroaki

    1997-01-01

    X-ray characteristics including subject thickness (copper plate), tube voltage, tube current and irradiation time were measured at stability, with an automatic dose control x-ray generator for cineangiography. Regardless of subject thickness, it is possible that the energy input to the x-ray tube in one frame may be decreased. The automatic control response was measured after rapid fluctuation in subject thickness. Two inverter-type x-ray generators with different automatic control units were studied. The older control unit changes exposure dose by tube voltage and tube current, while the newer one changes exposure dose by tube voltage, tube current and irradiation time. The maximum rate of change in tube voltage is greater with the newer control unit. In addition, the actual tube current response of the newer control unit in increasing nominal value is faster than the older one. In the new control unit, for each pulse, irradiation is cut off by means of a signal that the exposure has reached the proper value. Thus given the same differential in subject thickness, the newer control unit resumed stability faster than the older one. (author)

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

    International Nuclear Information System (INIS)

    1975-01-01

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

  11. The influence of parameters of A-type carbonated apatites synthesis on radiation dose response

    International Nuclear Information System (INIS)

    Oliveira, Liana Macedo de; Lopes, Ricardo Tadeu

    2000-01-01

    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 CO 2 - species (g perp = 2.0028 and g // = 1.9973) and CO 3 - species (g 1 = 2,0170, g 2 = 2,0090 e g 3 = 2,0041). The production of CO 2 - 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)

  12. Mathematical modeling improves EC50 estimations from classical dose-response curves.

    Science.gov (United States)

    Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

    2015-03-01

    The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

  13. Response to booster doses of hepatitis B vaccine among young adults who had received neonatal vaccination.

    Directory of Open Access Journals (Sweden)

    Paul K S Chan

    Full Text Available Newborns who have received hepatitis B immunization in 1980s are now young adults joining healthcare disciplines. The need for booster, pre- and post-booster checks becomes a practical question.The aim of this study is to refine the HBV vaccination policy for newly admitted students in the future.A prospective study on medical and nursing school entrants to evaluate hepatitis B serostatus and the response to booster doses among young adults.Among 212 students, 17-23-year-old, born after adoption of neonatal immunization, 2 (0.9% were HBsAg positive, 40 (18.9% were anti-HBs positive. At 1 month after a single-dose booster for anti-HBs-negative students, 14.5% had anti-HBs 100 mIU/mL, respectively. The anti-HBs levels were significantly higher for females than males (mean [SD]: 431 [418] vs. 246 [339] mIU/mL, P = 0.047. At 2-4 month after the third booster dose, 97.1% had anti-HBs >100 mIU/mL and 2.9% had 10-100 mIU/mL.Pre-booster check is still worthwhile to identify carriers among newly recruited healthcare workers born after adoption of neonatal immunization. A 3-dose booster, rather than a single dose, is required for the majority to achieve an anti-HBs level >100 mIU/mL, as memory immunity has declined in a substantial proportion of individuals. Cost-effectiveness of post-booster check for anti-HBs is low and should be further evaluated based on contextual specific utilization of results.

  14. PSOD: an interactive Fortran program to simulate the radiation dose response of membrane populations

    International Nuclear Information System (INIS)

    Perry, K.A.; Szekely, J.G.

    1982-04-01

    Program PSOD was written to simulate the distribution in responses of membrane populations subjected to random radiation doses and dose rates. It computes the response (damage) according to one of three formulas selected by the user, and outputs statistical results to the terminal. It will plot simulated dose- and response-frequency distributions in two or three dimensions. Doses and dose rates are selected from the log normal distribution; other distributions can be incorporated as the need arises. A true log normal curve with defined mean and standard deviation can also be generated. The purpose of this documentation is to provide a complete operating manual for the program. A user guide is available on-line after initiating a session of PSOD. Detailed examinations of the statistical validity of various steps have been included to aid future modifications and updating

  15. No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

    International Nuclear Information System (INIS)

    Sheehan, Daniel M.

    2006-01-01

    We tested the hypothesis that no threshold exists when estradiol acts through the same mechanism as an active endogenous estrogen. A Michaelis-Menten (MM) equation accounting for response saturation, background effects, and endogenous estrogen level fit a turtle sex-reversal data set with no threshold and estimated the endogenous dose. Additionally, 31 diverse literature dose-response data sets were analyzed by adding a term for nonhormonal background; good fits were obtained but endogenous dose estimations were not significant due to low resolving power. No thresholds were observed. Data sets were plotted using a normalized MM equation; all 178 data points were accommodated on a single graph. Response rates from ∼1% to >95% were well fit. The findings contradict the threshold assumption and low-dose safety. Calculating risk and assuming additivity of effects from multiple chemicals acting through the same mechanism rather than assuming a safe dose for nonthresholded curves is appropriate

  16. Postoperative analgesia in laparoscopic surgeries with small dose of preemptive ketamine: A comparative study of three small doses

    OpenAIRE

    Vaijayanti Nitin Gadre; Ninad Sunil Dhokte

    2017-01-01

    Introduction: Preemptive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine inhibits central sensitization in response to peripheral nociception. The purpose of our study was to compare efficacy of three small doses of ketamine for improving postoperative analgesia after laparoscopic surgeries. Materials and Methods: A total of 120 patients of American Society of Anesthesiologists physical status I–II undergoing laparoscopic surgeries were randomly allocated into four groups. Groups...

  17. The continual reassessment method: comparison of Bayesian stopping rules for dose-ranging studies.

    Science.gov (United States)

    Zohar, S; Chevret, S

    2001-10-15

    The continual reassessment method (CRM) provides a Bayesian estimation of the maximum tolerated dose (MTD) in phase I clinical trials and is also used to estimate the minimal efficacy dose (MED) in phase II clinical trials. In this paper we propose Bayesian stopping rules for the CRM, based on either posterior or predictive probability distributions that can be applied sequentially during the trial. These rules aim at early detection of either the mis-choice of dose range or a prefixed gain in the point estimate or accuracy of estimated probability of response associated with the MTD (or MED). They were compared through a simulation study under six situations that could represent the underlying unknown dose-response (either toxicity or failure) relationship, in terms of sample size, probability of correct selection and bias of the response probability associated to the MTD (or MED). Our results show that the stopping rules act correctly, with early stopping by using the two first rules based on the posterior distribution when the actual underlying dose-response relationship is far from that initially supposed, while the rules based on predictive gain functions provide a discontinuation of inclusions whatever the actual dose-response curve after 20 patients on average, that is, depending mostly on the accumulated data. The stopping rules were then applied to a data set from a dose-ranging phase II clinical trial aiming at estimating the MED dose of midazolam in the sedation of infants during cardiac catheterization. All these findings suggest the early use of the two first rules to detect a mis-choice of dose range, while they confirm the requirement of including at least 20 patients at the same dose to reach an accurate estimate of MTD (MED). A two-stage design is under study. Copyright 2001 John Wiley & Sons, Ltd.

  18. Low-Dose Radiation-Induced Adaptive Response in Polychromatic Mice Erythrocyte as Measured by Acridine Orange Stained Micronuleus Assay

    International Nuclear Information System (INIS)

    Hee-Sun, K.; Kwang-Hee, Y.; Cha-Soom, K.; Jung-Mi, C.; Gu-Choul, S.; Suk-Young, P.; Kyoung-H, C.; Chong-Soom, K.; Young-Khi, L.; Jae-Ho, W.

    2004-01-01

    The effect of conditioning pretreatment with 0.01Gy of gamma rays on micronucleated polychromatic erythrocyte (MN-PCE) induction by 2Gy of g-rays was determined in peripheral blood of C3H/He mice. The timing of their administration of challenge doses was 6hr. The response was determined by scoring of Acridine orange dye stained MN-PCEs. The results indicate that low dose gamma ray pretreatment does protect against MN-PCE induction by the challenge g-ray dose. Introduction: An adaptive response induced by low doses of ionizing radiation in vivo reported. Some research team reports that a reduction on MN-PCE of mice caused by the pretreatment was observed [1- 4]. However, there was variability in the amount of the response depending on the time and adaptive dose [3]. This is important because the variation of MN-PCE frequency with time could lead to differences in the interpretation. In this study, differences in the biological effects within the priming dose ranges are discussed. Materials and Methods: Specific pathogen free 5-week-old C3H/He mice, purchased from Shizuoka Laboratory Center (Japan), were kept in clean and conventional environment. When 6 weeks old, the animal were whole body irradiated using irradiator of IBL-437 (137Cs, 0.8Gy/min). After various time intervals, the two groups were administrated to adaptation dose and challenge dose of 0.01Gy and 2Gy, respectively. For experiments, sham-irradiated, only adaptive and challenge dose irradiated groups were run concurrently. Smears were stained and scored using Acridine orange dye method [2]. Statistically significant differences in MN-PCE frequency were determined by comparing tie individual values at each group with the respective control values (challenge dose irradiated group) by using the paired ttest. Results and Discussions: Induced MN by the challenge dose (2Gy) after the pretreatment with 0.01Gy is low to the one induced by the challenge dose alone. In the present study, this estimation for the

  19. Quality and Kinetics of the Antibody Response in Mice after Three Different Low-Dose Influenza Virus Vaccination Strategies▿

    OpenAIRE

    Hauge, Solveig; Madhun, Abdullah; Cox, Rebecca Jane; Haaheim, Lars Reinhardt

    2007-01-01

    The threat of a new influenza pandemic has led to renewed interest in dose-sparing vaccination strategies such as intradermal immunization and the use of adjuvanted vaccines. In this study we compared the quality and kinetics of the serum antibody response elicited in mice after one or two immunizations with a split influenza A (H3N2) virus, using three different low-dose vaccination strategies. The mice were divided into four groups, receiving either a low-dose vaccine (3 μg hemagglutinin [H...

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

    International Nuclear Information System (INIS)

    Englehardt, F.R.; Holliday, M.G.

    1981-01-01

    Acute toxicity effects of sulphur dioxide are reviewed, and the derivation of a dose-lethality curve (presented as LC 50 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)

  1. Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response

    International Nuclear Information System (INIS)

    Skwarchuk, Mark W.; Jackson, Andrew; Zelefsky, Michael J.; Venkatraman, Ennapadam S.; Cowen, Didier M.; Levegruen, Sabine; Burman, Chandra M.; Fuks, Zvi; Leibel, Steven A.; Ling, C. Clifton

    2000-01-01

    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

  2. Origin of the linearity no threshold (LNT) dose-response concept.

    Science.gov (United States)

    Calabrese, Edward J

    2013-09-01

    This paper identifies the origin of the linearity at low-dose concept [i.e., linear no threshold (LNT)] for ionizing radiation-induced mutation. After the discovery of X-ray-induced mutations, Olson and Lewis (Nature 121(3052):673-674, 1928) proposed that cosmic/terrestrial radiation-induced mutations provide the principal mechanism for the induction of heritable traits, providing the driving force for evolution. For this concept to be general, a LNT dose relationship was assumed, with genetic damage proportional to the energy absorbed. Subsequent studies suggested a linear dose response for ionizing radiation-induced mutations (Hanson and Heys in Am Nat 63(686):201-213, 1929; Oliver in Science 71:44-46, 1930), supporting the evolutionary hypothesis. Based on an evaluation of spontaneous and ionizing radiation-induced mutation with Drosophila, Muller argued that background radiation had a negligible impact on spontaneous mutation, discrediting the ionizing radiation-based evolutionary hypothesis. Nonetheless, an expanded set of mutation dose-response observations provided a basis for collaboration between theoretical physicists (Max Delbruck and Gunter Zimmer) and the radiation geneticist Nicolai Timoféeff-Ressovsky. They developed interrelated physical science-based genetics perspectives including a biophysical model of the gene, a radiation-induced gene mutation target theory and the single-hit hypothesis of radiation-induced mutation, which, when integrated, provided the theoretical mechanism and mathematical basis for the LNT model. The LNT concept became accepted by radiation geneticists and recommended by national/international advisory committees for risk assessment of ionizing radiation-induced mutational damage/cancer from the mid-1950s to the present. The LNT concept was later generalized to chemical carcinogen risk assessment and used by public health and regulatory agencies worldwide.

  3. Improvement of accident dose consequences simulation software for nuclear emergency response applications

    International Nuclear Information System (INIS)

    Cheng, Y.-H.; Shih Chunkuan; Jiang, S.-C.; Weng, T.-L.

    2008-01-01

    This study integrated the nuclear power plant simulation software, PCTRAN, with an atmospheric diffusion model to efficiently evaluate a nuclear power plant accident and its off-site dose consequences. PCTRAN, with its user-friendly interface, provides a fast simulation scheme that can simulate many kinds of nuclear power plant accidents. Once accident initiation events are activated in the software, the plant parameters are calculated and displayed via animations on the user interface. Based on the simulated plant conditions, the radioactive materials considered in the software may be released from the plant to the environment. In this study, a dispersion algorithm, including a modified atmospheric diffusion model and its programming method, is proposed such that PCTRAN satisfies the application requirements to be used to plan nuclear emergency responses. First, the modified atmospheric diffusion model handles the variations of meteorological conditions (wind direction, wind velocity, and stability category) during a nuclear power plant accident simulation. Furthermore, the proposed programming method promotes calculation capability and efficiency by reducing the computational burden. For demonstration purposes, a postulated accident event was simulated for the Maanshan Nuclear Power Plant in Taiwan. The overall accident evolution, whole plant response, and off-site dose consequences could be predicted much earlier than what actually occurs. The thyroid and whole body dose rates (and their accumulations) as a function of accident time are displayed on the map within the emergency planning zone (EPZ). The influence of the accident on the off-site area can thus be estimated earlier, and the emergency classification can be determined by referring to the emergency action levels (EALs) for a quick nuclear emergency response

  4. The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection.

    Directory of Open Access Journals (Sweden)

    Ana Filipovic

    Full Text Available Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1×102, 1×104, and 1×106 inclusion forming units (IFUs. Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4+ and CD8+ cells within guinea pigs' submandibular lymph node (SMLN lymphocytes while the higher doses increased the percentages of CD4+ and CD8+ cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4+ and CD8+ cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1×104, and 1×106 IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections.

  5. 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

  6. Exposure dose response relationships of the freshwater bivalve Hyridella australis to cadmium spiked sediments

    International Nuclear Information System (INIS)

    Marasinghe Wadige, Chamani P.M.; Maher, William A.; Taylor, Anne M.; Krikowa, Frank

    2014-01-01

    organisms, which suggests that H. australis has some tolerance to cadmium. The metallothionein like protein fraction played an important role in the sequestration and detoxification of cadmium and the amount sequestered in this fraction increased with increased cadmium exposure. The highest percentage of biologically active cadmium was associated with the lysosome + microsome and mitochondrial fractions. Cadmium concentrations in these two fractions of cadmium exposed organisms were significantly higher with respect to controls. Total antioxidant capacity decreased with increased cadmium exposure and tissue dose. Lipid peroxidation increased and lysosomal membrane stability decreased significantly with increased cadmium exposure and tissue dose. Based on exposure–dose–response analysis in this study, H. australis would be a suitable organism for assessing cadmium sediment exposure and toxicity

  7. 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

    organisms, which suggests that H. australis has some tolerance to cadmium. The metallothionein like protein fraction played an important role in the sequestration and detoxification of cadmium and the amount sequestered in this fraction increased with increased cadmium exposure. The highest percentage of biologically active cadmium was associated with the lysosome + microsome and mitochondrial fractions. Cadmium concentrations in these two fractions of cadmium exposed organisms were significantly higher with respect to controls. Total antioxidant capacity decreased with increased cadmium exposure and tissue dose. Lipid peroxidation increased and lysosomal membrane stability decreased significantly with increased cadmium exposure and tissue dose. Based on exposure–dose–response analysis in this study, H. australis would be a suitable organism for assessing cadmium sediment exposure and toxicity.

  8. Dose response of alanine and methyl alanine towards gamma and in-situ alpha irradiation

    International Nuclear Information System (INIS)

    Mohapatra, M.; Rajeswari, B.; Bhide, M.K.; Rane, Vinayak; Kadam, R.M.

    2017-01-01

    In situ alpha and external gamma dose response of two ESR (electron spin resonance) dosimetric materials namely alanine and methyl alanine were investigated. It was observed that alanine dosimeter had a better dose response in comparison to methyl alanine for the in-situ alpha irradiation by using 239 Pu powder. On the other hand, in case of gamma radiation, methyl alanine was found to have the sensitivity as twice that of alanine. (author)

  9. A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

    Science.gov (United States)

    Chiu, Weihsueh A; Slob, Wout

    2015-12-01

    When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

  10. Studies of absorbed dose determinations and spatial dose distributions for high energy proton beams

    International Nuclear Information System (INIS)

    Hiraoka, Takeshi

    1982-01-01

    Absolute dose determinations were made with three types of ionization chamber and a Faraday cup. Methane based tissue equivalent (TE) gas, nitrogen, carbon dioxide, air were used as an ionizing gas with flow rate of 10 ml per minute. Measurements were made at the entrance position of unmodulated beams and for a beam of a spread out Bragg peak at a depth of 17.3 mm in water. For both positions, the mean value of dose determined by the ionization chambers was 0.993 +- 0.014 cGy for which the value of TE gas was taken as unity. The agreement between the doses estimated by the ionization chambers and the Faraday cup was within 5%. Total uncertainty estimated in the ionization chamber and the Faraday cup determinations is 6 and 4%, respectively. Common sources of error in calculating the dose from ionization chamber measurements are depend on the factors of ion recombination, W value, and mass stopping power ratio. These factors were studied by both experimentally and theoretically. The observed values for the factors show a good agreement to the predicted one. Proton beam dosimetry intercomparison between Japan and the United States was held. Good agreement was obtained with standard deviation of 1.6%. The value of the TE calorimeter is close to the mean value of all. In the proton spot scanning system, lateral dose distributions at any depth for one spot beam can be simulated by the Gaussian distribution. From the Gaussian distributions and the central axis depth doses for one spot beam, it is easy to calculate isodose distributions in the desired field by superposition of dose distribution for one spot beam. Calculated and observed isodose curves were agreed within 1 mm at any dose levels. (J.P.N.)

  11. Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE.

    Science.gov (United States)

    Ilan, Ezgi; Sandström, Mattias; Wassberg, Cecilia; Sundin, Anders; Garske-Román, Ulrike; Eriksson, Barbro; Granberg, Dan; Lubberink, Mark

    2015-02-01

    of 170 Gy. The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  12. Transcriptional Response in Mouse Thyroid Tissue after 211At Administration: Effects of Absorbed Dose, Initial Dose-Rate and Time after Administration.

    Directory of Open Access Journals (Sweden)

    Nils Rudqvist

    Full Text Available 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. However, a limitation has been the preferential accumulation of released 211At in the thyroid gland, which is a critical organ for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on genome-wide transcriptional expression in mouse thyroid gland.BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean thyroid absorbed doses of 0.023, 0.32, and 1.8 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively; mean thyroid absorbed dose was 1.4 Gy. Total RNA was extracted from pooled thyroids and the Illumina RNA microarray platform was used to determine mRNA levels. Differentially expressed transcripts and enriched GO terms were determined with adjusted p-value 1.5, and p-value <0.05, respectively.In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose at 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. Furthermore, similar regulation profiles were seen for groups administered 1.7 kBq. Interestingly, few previously proposed radiation responsive genes were detected in the present study. Regulation of immunological processes were prevalent at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy.

  13. Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose-response effect favoring preoperative treatment

    International Nuclear Information System (INIS)

    Glimelius, Bengt; Isacsson, Ulf; Jung, Bo; Paahlman, Lars

    1997-01-01

    Purpose: This study explored the relationship between radiation dose and reduction in local recurrence rate after preoperative and postoperative radiotherapy in rectal cancer. Methods and Materials: All randomized trials initiated prior to 1988 comparing preoperative and postoperative radiotherapy with surgery alone or with each other were included. Local failure rates were available in 5626 randomized patients. The linear quadratic formula was used to compensate for different radiotherapy schedules. Results: For preoperative radiotherapy, a clear dose-response relationship could be established. For postoperative radiotherapy, the range of doses was narrow, and a dose-response relationship could not be demonstrated. At similar doses, preoperative radiotherapy appeared to be more efficient in reducing local failure rate than postoperative. The only trial comparing preoperative with postoperative radiotherapy confirms this notion. A 15-20 Gy higher dose may be required postoperatively than preoperatively to reach similar efficacy. Neither approach alone significantly influences survival, although it is likely that a small survival benefit may be seen after preoperative radiotherapy. Conclusions: The information from the entire randomized experience suggests that preoperative radiotherapy may be more dose efficient than postoperative radiotherapy

  14. Radiation-induced apoptosis in human tumor cell lines: adaptive response and split-dose effect.

    Science.gov (United States)

    Filippovich, I V; Sorokina, N I; Robillard, N; Lisbona, A; Chatal, J F

    1998-07-03

    Irradiation of human ovarian carcinoma cells (OVCAR 3) and myeloma cells (RPMI 8226) with graded doses of 137Cs-gamma-rays led to a 35-40% increase in time-dependent apoptosis 72 hr after 6-8 Gy irradiation. Large individual variations in sensitivity to radiation-induced apoptosis were noted in human lymphocytes obtained from 5 donors. Pretreatment of OVCAR 3 and RPMI 8226 cells with 0.01 Gy increased their resistance to apoptosis after subsequent 6 Gy irradiation several hours or 48 and 72 hr later. A dose of 4 or 8 Gy given in 2 equal fractions at an interval of a few hours produced a low level of apoptosis compared to that resulting from a single administration of the same total dose. Adaptive response was demonstrated in 2 out of 3 samples of human lymphocytes isolated from different donors, and no split-dose effect for apoptosis was noted in 2 other donors. In split-dose experiments, there was no correlation between the sensitivity of cells to apoptosis and their position in the cell cycle, after the first half-dose. No G1 block was observed in irradiated cell lines. Adaptive response and split-dose effect were prevented by 3-aminobenzamide and okadaic acid which inhibit poly(ADP-ribose)polymerase and protein phosphatase, respectively. These results imply a common mechanism for acquired resistance to radiation-induced apoptosis in adaptive response and the split-dose effect.

  15. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Eric Y. Chuang

    2006-08-31

    It has been long recognized that a significant fraction of the radiation-induced genetic damage to cells are caused by secondary oxidative species. Internal cellular defense systems against oxidative stress play significant roles in countering genetic damage induced by ionizing radiation. The role of the detoxifying enzymes may be even more prominent in the case of low-dose, low-LET irradiation, as the majority of genetic damage may be caused by secondary oxidative species. In this study we have attempted to decipher the roles of the superoxide dismutase (SOD) genes, which are responsible for detoxifying the superoxide anions. We used adenovirus vectors to deliver RNA interference (RNAi or siRNA) technology to down-regulate the expression levels of the SOD genes. We have also over-expressed the SOD genes by use of recombinant adenovirus vectors. Cells infected with the vectors were then subjected to low dose γ-irradiation. Total RNA were extracted from the exposed cells and the expression of 9000 genes were profiled by use of cDNA microarrays. The result showed that low dose radiation had clear effects on gene expression in HCT116 cells. Both over-expression and down-regulation of the SOD1 gene can change the expression profiles of sub-groups of genes. Close to 200 of the 9000 genes examined showed over two-fold difference in expression under various conditions. Genes with changed expression pattern belong to many categories that include: early growth response, DNA-repair, ion transport, apoptosis, and cytokine response.

  16. Low-Dose UVA Radiation-Induced Adaptive Response in Cultured Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zhongrong Liu

    2012-01-01

    Full Text Available Objective. To investigate the mechanism of the adaptive response induced by low-dose ultraviolet A (UVA radiation. Methods. Cultured dermal fibroblasts were irradiated by a lethal dose of UVA (86.4 J/cm2 with preirradiation of single or repetitive low dose of UVA (7.2 J/cm2. Alterations of cellular morphology were observed by light microscope and electron microscope. Cell cycle and cellular apoptosis were assayed by flow cytometer. The extent of DNA damage was determined by single-cell gel electrophoresis (SCGE. Results. The cultured dermal fibroblasts, with pretreatment of single or repetitive irradiation of 7.2 J/cm2 UVA relieved toxic reaction of cellular morphology and arrest of cell cycle, decreased apoptosis ratio, reduced DNA chain breakage, and accelerated DNA repair caused by subsequent 86.4 J/cm2 UVA irradiation. Compared with nonpretreatment groups, all those differences were significant (P<0.01 or P<0.05. Conclusions. The adaptation reaction might depend on the accumulated dose of low-dose UVA irradiation. Low-dose UVA radiation might induce adaptive response that may protect cultured dermal fibroblasts from the subsequent challenged dose of UVA damage. The duration and protective capability of the adaptive reaction might be related to the accumulated dose of low-dose UVA Irradiation.

  17. NRC source term assessment for incident response dose projections

    International Nuclear Information System (INIS)

    Easley, P.; Pasedag, W.

    1984-01-01

    The NRC provides advice and assistance to licensees and State and local authorities in responding to accidents. The TACT code supports this function by providing source term projections for two situations during early (15 to 60 minutes) accident response: (1) Core/containment damage is indicated, but there are no measured releases. Quantification of a predicted release permits emergency response before people are exposed. With TACT, response personnel can estimate releases based on fuel and cladding conditions, coolant boundary and containment integrity, and mitigative systems operability. For this type of estimate, TACT is intermediate between default assumptions and time-consuming mechanistic codes. (2) A combination of plant status and limited release data are available. For this situation, iterations between predictions based on known conditions which are compared to measured releases gives reasonable confidence in supplemental source term information otherwise unavailable: nuclide mix, releases not monitored, and trending or abrupt changes. The assumptions and models used in TACT, and examples of its use, are given in this paper

  18. Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam

    Science.gov (United States)

    Gonçalves Filho, Luiz C.; Monte, David S.; Barros, Fabio R.; Santos, Luiz A. P.

    2018-01-01

    MOSFET can operate as a radiation detector mainly in high-energy photon beams, which are normally used in cancer treatments. In general, such an electronic device can work as a dosimeter from threshold voltage shift measurements. The purpose of this article is to show a new way for measuring the dose-response of MOSFETs when they are under X-ray beams generated from 100kV potential range, which is normally used in diagnostic radiology. Basically, the method consists of measuring the MOSFET drain current as a function of the radiation dose. For this the type of device, it has to be biased with a high value resistor aiming to see a substantial change in the drain current after it has been irradiated with an amount of radiation dose. Two types of N channel device were used in the experiment: a signal transistor and a power transistor. The delivered dose to the device was varied and the electrical curves were plotted. Also, a sensitivity analysis of the power MOSFET response was made, by varying the tube potential of about 20%. The results show that both types of devices have responses very similar, the shift in the electrical curve is proportional to the radiation dose. Unlike the power MOSFET, the signal transistor does not provide a linear function between the dose rate and its drain current. We also have observed that the variation in the tube potential of the X-ray equipment produces a very similar dose-response.

  19. Mass shootings: a meta-analysis of the dose-response relationship.

    Science.gov (United States)

    Wilson, Laura C

    2014-12-01

    A meta-analysis was conducted to examine the dose-response theory as it relates to posttraumatic stress symptoms (PTSSs) following mass shootings. It was hypothesized that greater exposure to a mass shooting would be associated with greater PTSSs. Trauma exposure in the current study was broadly defined as the extent to which a person experienced or learned about a mass shooting. The meta-analysis identified 11 qualifying studies that included 13 independent effect sizes from a total of 8,047 participants. The overall weighted mean effect size, based on a random effects model, was r = .19, p shooting on the relationship between exposure and PTSSs. Because so few studies satisfied the inclusion criteria, the present study also documents that this area of the literature is underresearched. Copyright © 2014 International Society for Traumatic Stress Studies.

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

    International Nuclear Information System (INIS)

    Sevil, U.A.; Gueven, O.; Slezsak, I.

    2002-01-01

    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

  1. Response of eggplant crop fertigated with doses of nitrogen and potassium

    Directory of Open Access Journals (Sweden)

    Álvaro H. C. de Souza

    Full Text Available ABSTRACT The objective of the present study was to evaluate the response of eggplant, cv. ‘Ciça’, with respect to yield, number of fruits and dry matter (root and stem, when grown in a greenhouse and conducted under fertigation with nitrogen and potassium. The experiment was conducted in the Irrigation Technical Center of the State University of Maringá, between the months of February and August 2015. Four nitrogen doses (0.0; 6.43; 12.86 and 25.72 g of N plant-1 and four potassium doses (0.0; 5.18; 10.36 and 20.73 g of K plant-1 were tested, totaling 16 treatments in a 4 x 4 factorial scheme, arranged in a completely randomized design with four replicates, in a Red Latosol with sandy texture. The highest number of fruits per plant and yield were found in the range of 14-17 g of N plant-1 (145-177 kg N ha-1. Single doses of potassium did not statistically influence yield and root dry matter.

  2. The use of biomarkers in psychiatric research: how serotonin transporter occupancy explains the dose-response curves of SSRIs.

    Science.gov (United States)

    Preskorn, Sheldon H

    2012-01-01

    This column reviews why signal detection in psychiatric research has been problematic, how the use of biomarkers can help, how and why fixed dose studies are done, and how these studies differ from what clinicians do in practice. The fixed dose studies done with selective serotonin reuptake inhibitors (SSRIs) are used to illustrate general points about clinical trial research methodology relevant to clinical practice. Studies with SSRIs have yielded flat dose-response curves with regard to efficacy but ascending dose-response curves with regard to discontinuation due to adverse effects. These clinical trial findings are explained by studies using serotonin transporter inhibition or occupancy as a surrogate marker for SSRI efficacy and tolerability. Initially, these studies were conducted ex vivo using human platelets as the model system; however, they have now been extended to in vivo measurement of serotonin transporter occupancy in patients using positron emission tomography. The conclusion from this work is that the usually effective, minimum dose of each marketed SSRI produces 70%-80% inhibition or occupancy (depending on the methodology used) of the serotonin transporter; higher rates of inhibition or occupancy do not on average increase efficacy but instead increase early discontinuation rates due to adverse effects. These increased discontinuation rates offset any gain in efficacy when the results are analyzed using the last-observation-carried-forward approach. An understanding of these principles also provides an explanation for what initially may appear to be a conundrum: why some patients can benefit from a dose increase even though, in fixed dose clinical trials, the drug had a flat dose-efficacy curve.

  3. A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection.

    Science.gov (United States)

    Melgaço, Juliana Gil; Morgado, Lucas Nóbrega; Santiago, Marta Almeida; Oliveira, Jaqueline Mendes de; Lewis-Ximenez, Lia Laura; Hasselmann, Bárbara; Cruz, Oswaldo Gonçalves; Pinto, Marcelo Alves; Vitral, Claudia Lamarca

    2015-07-31

    Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Effect of Photon Hormesis on Dose Responses to Alpha Particles in Zebrafish Embryos

    Directory of Open Access Journals (Sweden)

    Candy Yuen Ping Ng

    2017-02-01

    Full Text Available Photon hormesis refers to the phenomenon where the biological effect of ionizing radiation with a high linear energy transfer (LET value is diminished by photons with a low LET value. The present paper studied the effect of photon hormesis from X-rays on dose responses to alpha particles using embryos of the zebrafish (Danio rerio as the in vivo vertebrate model. The toxicity of these ionizing radiations in the zebrafish embryos was assessed using the apoptotic counts at 20, 24, or 30 h post fertilization (hpf revealed through acridine orange (AO staining. For alpha-particle doses ≥ 4.4 mGy, the additional X-ray dose of 10 mGy significantly reduced the number of apoptotic cells at 24 hpf, which proved the presence of photon hormesis. Smaller alpha-particle doses might not have inflicted sufficient aggregate damages to trigger photon hormesis. The time gap T between the X-ray (10 mGy and alpha-particle (4.4 mGy exposures was also studied. Photon hormesis was present when T ≤ 30 min, but was absent when T = 60 min, at which time repair of damage induced by alpha particles would have completed to prevent their interactions with those induced by X-rays. Finally, the drop in the apoptotic counts at 24 hpf due to photon hormesis was explained by bringing the apoptotic events earlier to 20 hpf, which strongly supported the removal of aberrant cells through apoptosis as an underlying mechanism for photon hormesis.

  5. Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.

    Science.gov (United States)

    Ruiz-Palacios, Guillermo M; Guerrero, M Lourdes; Bautista-Márquez, Aurora; Ortega-Gallegos, Hilda; Tuz-Dzib, Fernando; Reyes-González, Leticia; Rosales-Pedraza, Gustavo; Martínez-López, Julia; Castañón-Acosta, Erika; Cervantes, Yolanda; Costa-Clemens, SueAnn; DeVos, Beatrice

    2007-08-01

    Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine

  6. The dose-response analysis between BMI and common chronic diseases in northeast China.

    Science.gov (United States)

    Yu, Jianxing; Tao, Yuchun; Dou, Jing; Ye, Junsen; Yu, Yaqin; Jin, Lina

    2018-03-09

    High body mass index (BMI) predisposes to several chronic diseases, but a large-scale systematic and detailed study of dose-response relationship between BMI and chronic diseases has not been reported previously. In this study, we aimed to investigate the relationship between BMI and 3 chronic diseases (hypertension, dyslipidemia and MetS) in northeast China. A sample of 16412 participants aged 18~79 years old were included in Jilin province in 2012. The lambda-mu-sigma (LMS) method was applied to examine the trend of BMI by age, and the restricted cubic splines were used to investigate the non-linear associations (dose-response curve) between BMI and chronic diseases. It was pointed out that BMI increased rapidly when young, then kept steady in middle age, and finally declined slowly in old age, and accordingly age was divided into 3 segments, which were different by gender. The odds ratios (ORs) of BMI for the chronic diseases increased relatively slowly when young, then increased dramatically in middle-age and old population, especially for men. Further, the ORs of BMI among non-smokers were lower than those among smokers, and the same trend was shown to be more apparent among drinkers and non-drinkers. The risk of BMI for common chronic diseases increased dramatically in middle-aged, especially for men with drinking and smoking habits.

  7. Dose Response Association between Physical Activity and Biological, Demographic, and Perceptions of Health Variables

    Directory of Open Access Journals (Sweden)

    Paul D. Loprinzi

    2013-08-01

    Full Text Available Background: Few population-based studies have examined the association between physical activity (PA and cardiovascular disease risk factors, demographic variables, and perceptions of health status, and we do not have a clear understanding of the dose-response relationship among these variables. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey was used to examine the dose-response relationship between objectively measured PA and metabolic syndrome (and its individual cardiovascular disease risk factors, demographic variables, and perceptions of health. After exclusions, 5,538 participants 18 years or older were included in the present study, with 2,538 participants providing fasting glucose and 2,527 providing fasting triglyceride data. PA was categorized into deciles. Results: Overall, the health benefits showed a general pattern of increase with each increasing levels of PA. Of the ten PA classifications examined, participants in the highest moderate-to-vigorous physical activity (MVPA category (at least 71 min/day had the lowest odds of developing metabolic syndrome. Conclusion: At a minimum, sedentary adults should strive to meet current PA guidelines (i.e., 150 min/week of MVPA, with additional positive benefits associated with engaging in three times this level of PA.

  8. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    International Nuclear Information System (INIS)

    Audette-Stuart, M.; Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S.

    2011-01-01

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: → Frogs were collected from background and higher tritium level habitats. → The micronucleus assay was conducted on liver cells obtained from the frogs. → No detrimental effects were noted in frogs exposed to elevated tritium. → Adaptive responses were observed in frogs exposed to elevated tritium.

  9. Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment

    Energy Technology Data Exchange (ETDEWEB)

    Audette-Stuart, M., E-mail: stuartm@aecl.ca [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada); Kim, S.B.; McMullin, D.; Festarini, A.; Yankovich, T.L.; Carr, J.; Mulpuru, S. [Environmental Technologies Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1P0 (Canada)

    2011-06-15

    Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms. - Highlights: > Frogs were collected from background and higher tritium level habitats. > The micronucleus assay was conducted on liver cells obtained from the frogs. > No detrimental effects were noted in frogs exposed to elevated tritium. > Adaptive responses were observed in frogs exposed to elevated tritium.

  10. Blood pressure response to conventional and low-dose enalapril in chronic renal failure

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Heisterberg, Jens; Kamper, Anne-Lise

    2003-01-01

    AIMS: In chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present...... study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. METHODS: As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data...... potassium concentrations at day 90 and patients in the low group experienced a slight increase in GFR. CONCLUSIONS: In moderate to severe chronic renal insufficiency the same degree of blood pressure control was achieved on low as well as moderate daily doses of enalapril. This was irrespective...

  11. 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

  12. Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure.

    Science.gov (United States)

    Claussen, Catherine M; Dafny, Nachum

    2015-09-01

    The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long-term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization was also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals were observed for the 2.5 and 10.0mg/kg MPD exposed groups. For 2.5mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and

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

    Science.gov (United States)

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

    2009-01-01

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

  14. Introduction to methodology of dose-response meta-analysis for binary outcome: With application on software.

    Science.gov (United States)

    Zhang, Chao; Jia, Pengli; Yu, Liu; Xu, Chang

    2018-01-18

    Dose-response meta-analysis (DRMA) is widely applied to investigate the dose-specific relationship between independent and dependent variables. Such methods have been in use for over 30 years and are increasingly employed in healthcare and clinical decision-making. In this article, we give an overview of the methodology used in DRMA. We summarize the commonly used regression model and the pooled method in DRMA. We also use an example to illustrate how to employ a DRMA by these methods. Five regression models, linear regression, piecewise regression, natural polynomial regression, fractional polynomial regression, and restricted cubic spline regression, were illustrated in this article to fit the dose-response relationship. And two types of pooling approaches, that is, one-stage approach and two-stage approach are illustrated to pool the dose-response relationship across studies. The example showed similar results among these models. Several dose-response meta-analysis methods can be used for investigating the relationship between exposure level and the risk of an outcome. However the methodology of DRMA still needs to be improved. © 2018 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

  15. Radiation doses to children during modified barium swallow studies

    International Nuclear Information System (INIS)

    Weir, Kelly A.; McMahon, Sandra M.; Long, Gillian; Bunch, Judith A.; Pandeya, Nirmala; Coakley, Kerry S.; Chang, Anne B.

    2007-01-01

    There are minimal data on radiation doses to infants and children undergoing a modified barium swallow (MBS) study. To document screening times, dose area product (DAP) and effective doses to children undergoing MBS and to determine factors associated with increased screening times and effective dose. Fluoroscopic data (screening time, DAP, kVp) for 90 consecutive MBS studies using pulse fluoroscopy were prospectively recorded; effective dose was calculated and data were analyzed for effects of behavior, number of swallow presentations, swallowing dysfunction and medical problems. Mean effective dose for the entire group was 0.0826 ± 0.0544 mSv, screening time 2.48 ± 0.81 min, and DAP 28.79 ± 41.72 cGy cm 2 . Significant differences were found across three age groups (≤1.0, >1.0-3.0 and >3.0 years) for effective dose (mean 0.1188, 0.0651 and 0.0529 mSv, respectively; P < 0.001), but not for screening time or DAP. Effective dose was correlated with screening time (P 0.007), DAP (P < 0.001), number of swallow presentations (P = 0.007), lower age (P = 0.017), female gender (P = 0.004), and height (P < 0.001). Screening time was correlated with total number of swallow presentations (P < 0.001) and DAP (P < 0.001). Screening times, DAP, effective dose, and child and procedural factors associated with higher effective doses are presented for children undergoing MBS studies. (orig.)

  16. Radiation doses to children during modified barium swallow studies

    Energy Technology Data Exchange (ETDEWEB)

    Weir, Kelly A. [University of Queensland, Discipline of Paediatrics and Child Health, School of Medicine, Herston, Queensland (Australia); McMahon, Sandra M. [SpeechNet Speech Pathology Services, Brisbane (Australia); Long, Gillian; Bunch, Judith A. [Royal Children' s Hospital, Department of Medical Imaging, Herston (Australia); Pandeya, Nirmala [Queensland Institute of Medical Research, Herston (Australia); Coakley, Kerry S. [Biomedical Technology Services, Royal Brisbane and Women' s Hospital, Herston (Australia); Chang, Anne B. [Royal Children' s Hospital, Department of Respiratory Medicine, Herston (Australia)

    2007-03-15

    There are minimal data on radiation doses to infants and children undergoing a modified barium swallow (MBS) study. To document screening times, dose area product (DAP) and effective doses to children undergoing MBS and to determine factors associated with increased screening times and effective dose. Fluoroscopic data (screening time, DAP, kVp) for 90 consecutive MBS studies using pulse fluoroscopy were prospectively recorded; effective dose was calculated and data were analyzed for effects of behavior, number of swallow presentations, swallowing dysfunction and medical problems. Mean effective dose for the entire group was 0.0826 {+-} 0.0544 mSv, screening time 2.48 {+-} 0.81 min, and DAP 28.79 {+-} 41.72 cGy cm{sup 2}. Significant differences were found across three age groups ({<=}1.0, >1.0-3.0 and >3.0 years) for effective dose (mean 0.1188, 0.0651 and 0.0529 mSv, respectively; P < 0.001), but not for screening time or DAP. Effective dose was correlated with screening time (P = 0.007), DAP (P < 0.001), number of swallow presentations (P = 0.007), lower age (P = 0.017), female gender (P = 0.004), and height (P < 0.001). Screening time was correlated with total number of swallow presentations (P < 0.001) and DAP (P < 0.001). Screening times, DAP, effective dose, and child and procedural factors associated with higher effective doses are presented for children undergoing MBS studies. (orig.)

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

    International Nuclear Information System (INIS)

    Rungsimaphorn, B.; Rerkamnuaychoke, B.; Sudprasert, W.

    2014-01-01

    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 137 Cs 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.

  18. Micro-dosing for early biokinetic studies in humans

    International Nuclear Information System (INIS)

    Stenstroem, K.; Sydoff, M.; Mattsson, S.

    2010-01-01

    Micro-dosing is a new concept in drug development that-if implemented in the pharmaceutical industry-would mean that new drugs can be tested earlier in humans than done today. The human micro-dosing concept-or 'Phase 0'-may offer improved candidate selection, reduced failure rates in the drug development line and a reduction in the use of laboratory animals in early drug development, factors which will help to speed up drug development and also reduce the costs. Micro-dosing utilises sub-pharmacological amounts of the substance to open opportunities for early studies in man. Three technologies are used for micro-dosing: accelerator mass spectrometry (AMS), positr