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Sample records for lethal doses application

  1. Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV).

    PubMed

    McKenney, Douglas G; Kurath, Gael; Wargo, Andrew R

    2016-03-01

    The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50 values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout. PMID:26752429

  2. Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)

    USGS Publications Warehouse

    McKenney, Douglas; Kurath, Gael; Wargo, Andrew

    2016-01-01

    The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

  3. Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform

    SciTech Connect

    Philip, Binu K.; Anand, Sathanandam S.; Palkar, Prajakta S.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-10-01

    Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethal dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of {sup 14}C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of {sup 14}C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC{sub 15-360min}) in the systemic

  4. Determination of the median lethal dose of botulinum serotype E in channel catfish fingerlings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The median lethal dose of botulinum serotype E in 5.3-g channel catfish Ictalurus punctatus fingerlings was determined. Five tanks (five fish/tank) were assigned to each of the following treatment groups: 70, 50, 35, 25, or 15 pg of purified botulinum serotype E. Fish were injected intracoelomically...

  5. Protective effect of picolinic acid on mice intracerebrally infected with lethal doses of Candida albicans.

    PubMed Central

    Blasi, E; Mazzolla, R; Pitzurra, L; Barluzzi, R; Bistoni, F

    1993-01-01

    We have studied the effects of picolinic acid (PLA), a product of tryptophan degradation, on mouse susceptibility to intracerebral infection with Candida albicans. We show that intraperitoneal administration of PLA significantly enhances the median survival time of mice inoculated with the lethal challenge. Furthermore, intracerebral administration of this agent induces a protective state against the local lethal infection, the phenomenon depending upon the administration schedule and doses of PLA employed. According to survival data, yeast growth in the brain as well as yeast colonization of the kidneys are drastically reduced in PLA-treated mice compared with those for untreated controls. Northern (RNA) blot analysis of brain tissues demonstrates that mRNA levels specific for tumor necrosis factor and interleukin 1 are augmented and induced, respectively, after inoculation of PLA. These results indicate that PLA has a protective effect likely involving elicitation of a cytokine response in vivo against fungal infections. Images PMID:7506894

  6. Chloroquine improves survival and hematopoietic recovery following lethal low dose- rate radiation

    PubMed Central

    Lim, Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang, Yonggang; Yu, Hsiang-Hsuan M; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose We have previously shown that the anti-malarial agent chloroquine can abrogate the lethal cellular effects of low dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials C57BL/6 mice were irradiated with total of 12.8 Gy delivered at 9.4 cGy/hr. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hrs and 4 hrs before irradiation. Bone marrow cells isolated from tibia, fibula and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retro orbital injection. Chimerism was assessed by flow cytometry. In vitro methyl cellulose colony forming assay of whole bone marrow cells as well as FACS analysis of lineage depleted cells was used to assess the effect of chloroquine on progenitor cells. Results Mice pretreated with chloroquine prior to radiation exhibited a significantly higher survival rate compared to mice treated with radiation alone (80 vs.31 percent, p=0.0026). Chloroquine administration prior to radiation did not impact the survival of ATM null mice (p=0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after the transplantation (4.2 percent vs. 0.4 percent, p=0.015). Conclusion Chloroquine administration prior to radiation had a significant effect on the survival of normal but not ATM null mice strongly suggesting that the in vivo effect like the in vitro effect is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the

  7. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    SciTech Connect

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-11-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  8. Priming dose of phenylhydrazine protects against hemolytic and lethal effects of 2-butoxyethanol

    SciTech Connect

    Palkar, Prajakta S.; Philip, Binu K.; Reddy, Ramesh N.; Mehendale, Harihara M.

    2007-11-15

    Protection against a high dose of a toxicant by prior exposure to another toxicant is called heteroprotection. Our objective was to establish a heteroprotection model in RBCs. Female Sprague Dawley rats treated with an LD90 dose of 2-butoxyethanol (BE, 1500 mg/kg in water, 5 ml/kg po) 14 days after priming with 0.9% NaCl suffered 90% mortality by 15 days, whereas all rats receiving the LD90 dose of BE 14 days after priming with phenylhydrazine (PHZ, 125 mg/kg in 0.9% NaCl, 3 ml/kg po) survived. Hematocrit decreased from normal 45% to 24% by day 3 after PHZ priming and improved thereafter. Increasing the time interval between the priming and LD90 dose to 21 days abolished the heteroprotection. RBCs obtained on days 7 and 14 after PHZ priming unlike those on day 21 were resilient to the hemotoxic metabolite of BE, butoxyacetic acid (BAA). Unaltered hepatic alcohol and aldehyde dehydrogenase activities upon PHZ priming suggested that bioactivation of BE to BAA was unaffected. Lower renal (6 and 12 h) and hepatic (12 h) BAA levels and 3 fold higher excretion of BAA in PHZ-primed rat urine suggested a protective role of toxicokinetics. Higher erythropoietin, reticulocytes, and resiliency of PHZ-primed rat RBCs indicated that newly formed RBCs are resilient to hemolytic BAA. The antioxidant levels in the PHZ-primed rat RBCs did not indicate a protective role in heteroprotection. In conclusion, the resistance of PHZ-primed rats against BE-induced hemotoxicity and lethality is mediated by a combination of altered toxicokinetics, robust erythropoiesis, and resiliency of new RBCs.

  9. Rescue of fish exposed to a lethal dose of pathogen, by signals from sublethally exposed survivors.

    PubMed

    Mothersill, Carmel; Austin, Dawn; Fernandez-Palomo, Cristian; Seymour, Colin; Auchinachie, Niall; Austin, Brian

    2015-03-01

    Rainbow trout (Oncorhynchus mykiss, Walbaum) were challenged intraperitoneally with a sublethal dose of Vibrio anguillarum VIB1 and allowed to recover. Then, after 7 days, naïve fish, (designated as 'bystander' fish) which had never been exposed to the pathogen, were introduced to the same tank. These swam with the adapted (recovered) fish for 7 days before both groups and a control (never exposed directly to the pathogen or to recovered fish) group were exposed to a lethal dose of VIB1. Mortality records were 100% in the control group within 3 days, 47% in the adapted group and 60% in the unchallenged bystander group, which swam with the adapted group. In both the latter groups, the time to death of the non-surviving fish was attenuated. This inter-animal communication of signals has previously been documented for animals exposed to ionizing radiation. Assays of tissues from control, challenged and 'bystander fish exposed to the pathogen showed that a signal as yet unidentified but similar to that seen in bystanders to irradiated fish was being produced. This signal caused a sharp and transient increase in intracellular calcium and a decrease in clonogenicity in a well-characterized reporter assay. PMID:25757731

  10. Establishment of a mouse model of 70% lethal dose by total-body irradiation

    PubMed Central

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun

    2016-01-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model. PMID:27382380

  11. Materials Applications for Non-Lethal: Aqueous Foams

    SciTech Connect

    GOOLSBY,TOMMY D.; SCOTT,STEVEN H.

    1999-09-15

    High expansion aqueous foam is an aggregation of bubbles that has the appearance of soap suds and is used to isolate individuals both visually and acoustically. It was developed in the 1920's in England to fight coal mine fires and has been widely used since for fire fighting and dust suppression. It was developed at Sandia National Laboratories (SNL) in the 1970's for nuclear safeguards and security applications. In the mid-1990s, the National Institute of Justice (NIJ), the research arm of the Department of Justice, began a project with SNL to determine the applicability of high expansion aqueous foam for correctional applications. NIJ funded the project as part of its search for new and better less-than-lethal weapons for responding to violent and dangerous individuals, where other means of force could lead to serious injuries. The phase one objectives of the project were to select a low-to-no toxicity foam concentrate (foaming agent) with physical characteristics suited for use in a single cell or large prison disturbances, and to determine if the selected foam concentrate could serve as a carrier for Oleoresin Capsicum (OC) irritant. The phase two objectives were to conduct an extensive toxicology review of the selected foam concentrate and OC irritant, and to conduct respiration simulation experiments in the selected high expansion aqueous foam. The phase three objectives were to build a prototype individual cell aqueous foam system and to study the feasibility of aqueous foams for large prison facility disturbances. The phase four and five objectives were to use the prototype system to do large scale foam physical characteristics testing of the selected foam concentrate, and to have the prototype single cell system further evaluated by correctional representatives. Prison rather than street scenarios were evaluated as the first and most likely place for using the aqueous foam since prisons have recurrent incidents where officers and inmates might be

  12. Treatment of Irradiated Mice with High-Dose Ascorbic Acid Reduced Lethality

    PubMed Central

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure. PMID:25651298

  13. Physiological response of alligator gar juveniles (Atractosteus spatula) exposed to sub-lethal doses of pollutants.

    PubMed

    González, Carlos Aguilera; Cruz, Julio; Alfaro, Roberto Mendoza

    2015-08-01

    Alligator gar populations have declined because of overfishing, habitat loss and pollution. Over time, the exposure to different pollutants have affected these fishes as a consequence of their high trophic level, bottom-dwelling habits and long life span. In order to evaluate the physiological effects of pollutants on alligator gar, juveniles (6, 12 and 24 months) were exposed to sub-lethal doses of diazinon, β-naphthoflavone (BNF) and 17 β-estradiol (E2) by intraperitoneal injection. After 2 days of exposure, liver samples were taken to determine the activities of acetylcholinesterase, butyrylcholinesterase and carboxylesterase; alkaline and acid phosphatases (ALP and ACP); ethoxyresorufin o-deethylase (EROD); glutathione s-transferase (GST); superoxide dismutase (SOD), and vitellogenin (VTG) concentration. Two additional bioassays consisting on the exposure of compounds through water or food were performed and after 4 and 28 days, respectively, biomarkers were determined. All esterases were inhibited in organisms exposed to diazinon as well as in 6-months gar exposed to E2 and BNF. In contrast, ALP activity increased in gar exposed to diazinon and E2, while ACP activity did not show any variations. No EROD activity was registered after exposure to the different pollutants, despite being one of the most sensitive and common detoxification biomarkers used for fishes. GST activity reduction was detected when gar were exposed to E2 and BNF, while SOD activity increased after exposure to diazinon and E2. Finally, VTG levels were higher in animals exposed to E2 compared to other treatments. Overall, these results suggest that alligator gar juveniles have a low biotransformation metabolism and show that they are especially sensitive to those pollutants affecting the nervous system. PMID:25948055

  14. Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture.

    PubMed

    D'Alessio, Luciana; Pinto, Alipio; Cangelosi, Adriana; Geoghegan, Patricia A; Tironi-Farinati, Carla; Brener, Gabriela J; Goldstein, Jorge

    2016-01-01

    Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic-uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however, the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood-brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test), and ultrastructural analysis (transmission electron microscope). Intravenous administration of vehicle (control group), sub-lethal dose of 0.5 and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n = 6). Blood-brain barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1 ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance. PMID:26904009

  15. Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture

    PubMed Central

    Pinto, Alipio; Cangelosi, Adriana; Geoghegan, Patricia A.; Tironi-Farinati, Carla; Brener, Gabriela J.; Goldstein, Jorge

    2016-01-01

    Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic–uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however, the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood–brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test), and ultrastructural analysis (transmission electron microscope). Intravenous administration of vehicle (control group), sub-lethal dose of 0.5 and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n = 6). Blood–brain barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1 ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance. PMID:26904009

  16. Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance

    USGS Publications Warehouse

    Gutreuter, S.; Boogaard, M.A.

    2007-01-01

    Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2???,5???-dichloro-4???- nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4- nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software. ?? 2007 SETAC.

  17. A cytomegalovirus-based vaccine provides long-lasting protection against lethal Ebola virus challenge after a single dose

    PubMed Central

    Tsuda, Yoshimi; Parkins, Christopher J.; Caposio, Patrizia; Feldmann, Friederike; Botto, Sara; Ball, Susan; Messaoudi, Ilhem; Cicin-Sain, Luka; Feldmann, Heinz; Jarvis, Michael A.

    2015-01-01

    Ebola virus (Zaire ebolavirus; EBOV) is a highly lethal hemorrhagic disease virus that most recently was responsible for two independent 2014 outbreaks in multiple countries in Western Africa, and the Democratic Republic of the Congo, respectively. Herein, we show that a cytomegalovirus (CMV)-based vaccine provides durable protective immunity from Ebola virus following a single vaccine dose. This study has implications for human vaccination against ebolaviruses, as well as for development of a ‘disseminating’ vaccine to target these viruses in wild African great apes. PMID:25820063

  18. Determination of the Median Lethal Dose and Electrophoretic Pattern of Hottentotta saulcyi (Scorpiones, Buthidae) Scorpion Venom

    PubMed Central

    Yağmur, Ersen Aydın; Özkan, Özcan; Karaer, K Zafer

    2015-01-01

    Background: In this study, we investigated the lethal potency, electrophoretic protein pattern and in vivo effects of Hottentotta saulcyi scorpion venom in mice. Methods: Scorpions were collected at night, by using a UV lamp from Mardin Province, Turkey. Venom was obtained from mature H. saulcyi scorpions by electrical stimulation of the telson. The lethality of the venom was determined by i.v. injections using Swiss mice. In vivo effects of the venom were assessed by using the intraperitoneal route (ip) injections into mice (20±1g) and monitored for 24 h. The protein profiles of the scorpion venom were analyzed by NuPAGE® Novex® 4–12 % gradient Bis-Tris gel followed by Coomassie blue staining. Results: The lethal assay of the venom was 0.73 mg/kg in mice. We determined the electrophoretic protein pattern of this scorpion venom to be 4, 6, 9, 31, 35, 40, 46 and 69 kDa by SDS-PAGE. Analysis of electrophoresis indicated that H. saulcyi scorpion intoxicated mice exhibited autonomic nervous system symptoms (tachypnea, restlessness, hyperexcitability, convulsions, salivation, lacrimation, weakness). Conclusions: Hottentotta saulcyi scorpion venom includes short-chain neurotoxins and long-chain neurotoxins according to the electrophoretic protein patterns. The stings of H. saulcyi scorpion must be considered of risk for humans in the southeastern region, Turkey. PMID:26623435

  19. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    PubMed

    MacVittie, Thomas J; Farese, Ann M; Jackson, William

    2015-11-01

    Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

  20. Prophylaxis with human serum butyrylcholinesterase protects Göttingen minipigs exposed to a lethal high-dose of sarin vapor.

    PubMed

    Saxena, Ashima; Hastings, Nicholas B; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

    2015-08-01

    Serum-derived human butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a potential prophylactic nerve agent countermeasure. Previously, we reported the prophylactic efficacy of Hu BChE in Göttingen minipigs against a whole-body exposure to 4.1mg/m(3) of sarin (GB) vapor, which produced lethality over 60min. Since the toxicity of nerve agent is concentration-dependent, in the present study, we investigated the toxic effects of an almost 3-fold higher rate of GB vapor exposure and the ability of Hu BChE to protect minipigs against this exposure. Male minipigs were subjected to: (1) air exposure; (2) GB vapor exposure; or (3) pretreatment with 7.5mg/kg of Hu BChE by i.m. injection, 24h prior to whole-body exposure to 11.4mg/m(3) of GB vapor for 10min. Electrocardiogram, electroencephalogram, and pupil size were monitored throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB bound to red blood cells and plasma. A novel finding was that saline-treated animals exposed to GB vapor did not develop any seizures, but manifested a variety of cardiac and whole blood toxic signs and rapidly died due to respiratory failure. Strikingly, pre-treatment with 7.5mg/kg of Hu BChE not only prevented lethality, but also avoided all cardiac toxic signs manifested in the non-treated cohort. Thus, Hu BChE alone can serve as an effective prophylactic countermeasure versus a lethal high-dose exposure to GB vapor. PMID:26145887

  1. Clinical parameters, postmortem analysis and estimation of lethal dose in victims of a massive intoxication with diethylene glycol.

    PubMed

    Ferrari, Luis A; Giannuzzi, Leda

    2005-10-01

    could be observed. The lethal dose for human beings estimated in this work ranged from 0.014 to 0.170 mg DEG/kg body weight. This is a lower lethal dose than reported in a separate incident in Haiti. These results may contribute to the understanding of DEG's metabolic pathway and provides data from lethal doses in humans. PMID:15979833

  2. Core Body Temperature as Adjunct to Endpoint Determination in Murine Median Lethal Dose Testing of Rattlesnake Venom

    PubMed Central

    Cates, Charles C; McCabe, James G; Lawson, Gregory W; Couto, Marcelo A

    2014-01-01

    Median lethal dose (LD50) testing in mice is the ‘gold standard’ for evaluating the lethality of snake venoms and the effectiveness of interventions. As part of a study to determine the murine LD50 of the venom of 3 species of rattlesnake, temperature data were collected in an attempt to more precisely define humane endpoints. We used an ‘up-and-down’ methodology of estimating the LD50 that involved serial intraperitoneal injection of predetermined concentrations of venom. By using a rectal thermistor probe, body temperature was taken once before administration and at various times after venom exposure. All but one mouse showed a marked, immediate, dose-dependent drop in temperature of approximately 2 to 6 °C at 15 to 45 min after administration. The lowest temperature sustained by any surviving mouse was 33.2 °C. Surviving mice generally returned to near-baseline temperatures within 2 h after venom administration, whereas mice that did not survive continued to show a gradual decline in temperature until death or euthanasia. Logistic regression modeling controlling for the effects of baseline core body temperature and venom type showed that core body temperature was a significant predictor of survival. Linear regression of the interaction of time and survival was used to estimate temperatures predictive of death at the earliest time point and demonstrated that venom type had a significant influence on temperature values. Overall, our data suggest that core body temperature is a useful adjunct to monitoring for endpoints in LD50 studies and may be a valuable predictor of survival in venom studies. PMID:25527024

  3. The acute lethal dose 50 (LD50) of caffeine in albino rats.

    PubMed

    Adamson, Richard H

    2016-10-01

    An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single dose and the animals observed for a specified time period. Although conducting routine acute toxicity testing in rodents has been criticized, it can serve useful functions and also have practical implications. Material safety data sheets (MSDS) will reflect the acute toxicity of a substance and may require workers to wear protective gear, if appropriate, based on the LD50. There is no information in the scientific published literature which calculates a mean LD50 and standard deviation for caffeine administered orally to rats, using studies performed under good laboratory practice (GLP) or equivalent. This report does that and should be useful to manufacturers, packagers, transporters and regulators of this material. Using data from studies that are reproducible and reliable, the most accurate estimate of the acute LD50 of caffeine administered orally in male albino rats is hereby reported to be 367/mg/kg. PMID:27461039

  4. Photosensitized damage inflicted on plasma membranes of live cells by an extracellular generator of singlet oxygen--a linear dependence of a lethal dose on light intensity.

    PubMed

    Zarębski, Mirosław; Kordon, Magdalena; Dobrucki, Jurek W

    2014-01-01

    We describe a study of the influence of a dose rate, i.e. light intensity or photon flux, on the efficiency of induction of a loss of integrity of plasma membranes of live cells in culture. The influence of a photon flux on the size of the light dose, which was capable of causing lethal effects, was measured in an experimental system where singlet oxygen was generated exclusively outside of live cells by ruthenium(II) phenantroline complex. Instantaneous, sensitive detection of a loss of integrity of a plasma membrane was achieved by fluorescence confocal imaging of the entry of this complex into a cell interior. We demonstrate that the size of the lethal dose of light is directly proportional to the intensity of the exciting light. Thus, the probability of a photon of the exciting light inflicting photosensitized damage on plasma membranes diminishes with increasing density of the incident photons. PMID:24279807

  5. Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice.

    PubMed

    Pietzner, J; Merscher, B M; Baer, P C; Duecker, R P; Eickmeier, O; Fußbroich, D; Bader, P; Del Turco, D; Henschler, R; Zielen, S; Schubert, R

    2016-04-01

    Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a co-conditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atm-deficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model. PMID:26752140

  6. Median lethal dose determination for percutaneous exposure to soman and VX in guinea pigs and the effectiveness of decontamination with M291 SDK or SANDIA foam.

    PubMed

    Clarkson, Edward D; Schulz, Susan M; Railer, Roy F; Smith, Kelly H

    2012-08-01

    Soman (GD) and VX are chemical warfare agents that can be absorbed through the skin. We determined the median lethal dose (MLD) for the cutaneous application of GD and VX in anesthetized haired guinea pigs and then tested the ability of a currently fielded decontamination kit, the M291 Skin Decontamination Kit (SDK), and decontaminating foam made by SANDIA Labs to decontaminate areas that have been exposed to cutaneous applications of GD and VX. The fur of guinea pigs was clipped on the left flank 24h prior to exposure. Animals were anesthetized and 5 min later neat GD or neat VX was applied. The MLD for percutaneous exposure to GD was 11.6 mg/kg, and to VX it was 0.10mg/kg. To test the ability of the M291 SDK, either GD or VX was applied and removed 1 min later with the pads of the M291 SDK clasped in a pair of forceps and wiped across the flank of the animal. The MLDs for GD and VX removed with the M291 SDK pads were 76.9 mg/kg and 0.87 mg/kg, respectively. When neat GD or neat VX was applied and removed 1 min later in the same manner with gauze soaked in SANDIA foam (MDF-100), the MLDs were 412 mg/kg and 10.4 mg/kg respectively. These data demonstrate that GD and VX are significantly less potent when applied cutaneously than previously reported for subcutaneous injections and indicate that improvement is needed on the limited protective ratio provided by the M291 SDK. PMID:22698813

  7. Aqueous foam as a less-than-lethal technology for prison applications

    NASA Astrophysics Data System (ADS)

    Goolsby, Tommy D.

    1997-01-01

    High expansion aqueous foam is an aggregation of bubbles that has the appearance of soap suds and is used to isolate individuals both visually and acoustically. It was developed in the 1920's in England to fight coal mine fires and has been widely used since for fire fighting and dust suppression. It was developed at Sandia National Laboratories (SNL) in the 1970's for nuclear safeguards and security applications. In late 1994, the National Institute of Justice (NIJ), the research arm of the Department of Justice, began a project with SNL to determine the applicability of high expansion aqueous foam for correctional applications. NIJ funded the project as part of its search for new and better less-than-lethal weapons for responding to violent and dangerous individuals, where other means of force could lead to serious injuries. The phase one objectives of the project were to select a low-to-no toxicity foam concentrate with physical characteristics suited for use in a single cell or large prison disturbances, and to determine if the selected foam concentrate could serve as a carrier for Oleoresin Capsicum (OC) irritant. The phase two objective were to conduct an extensive toxicology review of the selected foam concentrate and OC irritant, and to conduct respiration simulation experiments in the selected high expansion aqueous foam. The phase three objectives were to build a prototype individual cell aqueous foam system and to study the feasibility of aqueous foams for large prison facility disturbances. The phase four and five objectives were to use the prototype system to do large scale foam physical characteristics testing of the selected foam concentrate, and to have the prototype single cell system further evaluated by correctional representatives. Prison rather than street scenarios were evaluated as the first and most likely place for using the aqueous foam since prisons have recurrent incidents where officers and inmates might be seriously injured during

  8. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose.

    PubMed

    Chahal, Jasdave S; Khan, Omar F; Cooper, Christopher L; McPartlan, Justine S; Tsosie, Jonathan K; Tilley, Lucas D; Sidik, Saima M; Lourido, Sebastian; Langer, Robert; Bavari, Sina; Ploegh, Hidde L; Anderson, Daniel G

    2016-07-19

    Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8(+) T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases. PMID:27382155

  9. A study of the shape of dose-response curves for acute lethality at low response: a megadaphnia study'

    SciTech Connect

    Sebaugh, J.L.; Wilson, J.D.; Tucker, M.W.; Adams, W.J. )

    1991-12-01

    Dose-response curves were developed for the immobilization response in Daphnia magna to four toxicants. The purpose of this work was to study the effect of the form of the model and the number of concentration levels used on the estimates of typical low-dose effective concentrations (1%, 5%, 10%). The generalized four-parameter logistic model was used as the reference. When using 12 concentration levels, one of the logistic family two- or three-parameter models was shown reliably to represent each of these various sets of dose-response data, and to provide adequate estimates of EC01 and EC05, as well as EC10 and EC50. For two of the toxicants, an asymmetric model was required. When reducing the number of concentrations to five, the EC10 and EC50 were well estimated by the probit model, with acceptable results at the EC05 level.

  10. Single-Dose Replication-Defective VSV-based Nipah Virus Vaccines Provide Protection from Lethal Challenge in Syrian Hamsters

    PubMed Central

    Lo, Michael K.; Bird, Brian H.; Chattopadhyay, Anasuya; Drew, Clifton P.; Martin, Brock E.; Coleman, Joann D.; Rose, John K.; Nichol, Stuart T.; Spiropoulou, Christina F.

    2013-01-01

    Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD50 NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans. PMID:24184127

  11. The Novel Application of Non-Lethal Citizen Science Tissue Sampling in Recreational Fisheries.

    PubMed

    Williams, Samuel M; Holmes, Bonnie J; Pepperell, Julian G

    2015-01-01

    Increasing fishing pressure and uncertainty surrounding recreational fishing catch and effort data promoted the development of alternative methods for conducting fisheries research. A pilot investigation was undertaken to engage the Australian game fishing community and promote the non-lethal collection of tissue samples from the black marlin Istiompax indica, a valuable recreational-only species in Australian waters, for the purpose of future genetic research. Recruitment of recreational anglers was achieved by publicizing the project in magazines, local newspapers, social media, blogs, websites and direct communication workshops at game fishing tournaments. The Game Fishing Association of Australia and the Queensland Game Fishing Association were also engaged to advertise the project and recruit participants with a focus on those anglers already involved in the tag-and-release of marlin. Participants of the program took small tissue samples using non-lethal methods which were stored for future genetic analysis. The program resulted in 165 samples from 49 participants across the known distribution of I. indica within Australian waters which was a sufficient number to facilitate a downstream population genetic analysis. The project demonstrated the potential for the development of citizen science sampling programs to collect tissue samples using non-lethal methods in order to achieve targeted research objects in recreationally caught species. PMID:26376487

  12. The Novel Application of Non-Lethal Citizen Science Tissue Sampling in Recreational Fisheries

    PubMed Central

    Williams, Samuel M.; Holmes, Bonnie J.; Pepperell, Julian G.

    2015-01-01

    Increasing fishing pressure and uncertainty surrounding recreational fishing catch and effort data promoted the development of alternative methods for conducting fisheries research. A pilot investigation was undertaken to engage the Australian game fishing community and promote the non-lethal collection of tissue samples from the black marlin Istiompax indica, a valuable recreational-only species in Australian waters, for the purpose of future genetic research. Recruitment of recreational anglers was achieved by publicizing the project in magazines, local newspapers, social media, blogs, websites and direct communication workshops at game fishing tournaments. The Game Fishing Association of Australia and the Queensland Game Fishing Association were also engaged to advertise the project and recruit participants with a focus on those anglers already involved in the tag-and-release of marlin. Participants of the program took small tissue samples using non-lethal methods which were stored for future genetic analysis. The program resulted in 165 samples from 49 participants across the known distribution of I. indica within Australian waters which was a sufficient number to facilitate a downstream population genetic analysis. The project demonstrated the potential for the development of citizen science sampling programs to collect tissue samples using non-lethal methods in order to achieve targeted research objects in recreationally caught species. PMID:26376487

  13. Modification of the brain proteome of Africanized honeybees (Apis mellifera) exposed to a sub-lethal doses of the insecticide fipronil.

    PubMed

    Roat, T C; dos Santos-Pinto, J R A; Dos Santos, L D; Santos, K S; Malaspina, O; Palma, M S

    2014-11-01

    Fipronil is a phenylpyrazole insecticide that is widely used in Brazilian agriculture for pest control. Although honeybees are not targets of fipronil, studies indicate that this pesticide can be harmful to honeybees. To assess the effects of fipronil in the brain of Africanized Apis mellifera workers, this study focused on the toxico-proteome profiling of the brain of newly emerged and aged honeybee workers that were exposed to a sub-lethal dose (10 pg fipronil per day. i.e. (1)/100 of LD50/bee/day during 5 days) of the insecticide. Proteomic analysis identified 25 proteins that were differentially up-regulated or down-regulated when the fipronil-exposed and non-exposed groups were compared. These proteins are potentially related to pathogen susceptibility, neuronal chemical stress, neuronal protein misfolding, and occurrence of apoptosis, ischemia, visual impairment, damaged synapse formation, brain degeneration, memory and learning impairment. The exposure of honeybees to a very low dose of fipronil, even for a short period of time (5 days), was sufficient to cause a series of important neuroproteomic changes in the brains of honeybees. PMID:25139030

  14. Bacterial Ghosts as an Oral Vaccine: a Single Dose of Escherichia coli O157:H7 Bacterial Ghosts Protects Mice against Lethal Challenge

    PubMed Central

    Mayr, Ulrike Beate; Haller, Christoph; Haidinger, Wolfgang; Atrasheuskaya, Alena; Bukin, Eugenij; Lubitz, Werner; Ignatyev, Georgy

    2005-01-01

    Enterohemorrhagic Escherichia coli (EHEC) is a bacterial pathogen that is associated with several life-threatening diseases for humans. The combination of protein E-mediated cell lysis to produce EHEC ghosts and staphylococcal nuclease A to degrade DNA was used for the development of an oral EHEC vaccine. The lack of genetic material in the oral EHEC bacterial-ghost vaccine abolished any hazard of horizontal gene transfer of resistance genes or pathogenic islands to resident gut flora. Intragastric immunization of mice with EHEC ghosts without the addition of any adjuvant induced cellular and humoral immunity. Immunized mice challenged at day 55 showed 86% protection against lethal challenge with a heterologous EHEC strain after single-dose oral immunization and 93.3% protection after one booster at day 28, whereas the controls showed 26.7% and 30% survival, respectively. These results indicate that it is possible to develop an efficacious single-dose oral EHEC bacterial-ghost vaccine. PMID:16040994

  15. Evaluation of the performance of three elastomers for non-lethal projectile applications

    NASA Astrophysics Data System (ADS)

    Thota, N.; Epaarachchi, J.; Lau, K. T.

    2015-09-01

    Less lethal kinetic ammunitions with soft noses such as eXact iMpact 1006, National Sports Spartan and B&T have been commonly used by military and law enforcement officers in the situations where lethal force is not warranted. In order to explore new materials to be used as nose in such ammunitions, a scholastic study using finite element simulations has been carried out to evaluate the effectiveness of two rubber like elastomers and a polyolefinic foam (low density, highly compressible, stiff and closed cell type of thermos plastic elastomer). State-of-the art thorax surrogate MTHOTA has been employed for the evaluation of blunt thoracic trauma. Force-rigid wall method was employed for the evaluation of head damage curves for each material. XM 1006 has been used as the benchmark projectile for the purpose of comparison. Both blunt thoracic trauma and head damage criterion point of view, both rubbers (R1 and R2) have yielded high values of VCmax and peak impact force. Polyolefinic foam (F1) considered in the study has yielded very promising VCmax values and very less peak impact force when compared with those of bench mark projectile XM 1006.

  16. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation

    PubMed Central

    2014-01-01

    Background The hematopoietic syndrome of the acute radiation syndrome (HSARS) is a life-threatening condition in humans exposed to total body irradiation (TBI); no drugs are approved for treating this condition. Recombinant human interleukin-12 (rHuIL-12) is being developed for HSARS mitigation under the FDA Animal Rule, where efficacy is proven in an appropriate animal model and safety is demonstrated in humans. Methods In this blinded study, rhesus monkeys (9 animals/sex/dose group) were randomized to receive a single subcutaneous injection of placebo (group 1) or rHuIL-12 at doses of 50, 100, 250, or 500 ng/kg (groups 2–5, respectively), without antibiotics, fluids or blood transfusions, 24–25 hours after TBI (700 cGy). Results Survival rates at Day 60 were 11%, 33%, 39%, 39%, and 50% for groups 1–5, respectively (log rank p < 0.05 for each dose vs. control). rHuIL-12 also significantly reduced the incidences of severe neutropenia, severe thrombocytopenia, and sepsis (positive hemoculture). Additionally, bone marrow regeneration following TBI was significantly greater in monkeys treated with rHuIL-12 than in controls. Conclusions Data from this study demonstrate that a single injection of rHuIL-12 delivered one day after TBI can significantly increase survival and reduce radiation-induced hematopoietic toxicity and infections. These data significantly advance development of rHuIL-12 toward approval under the Animal Rule as an effective stand-alone medical countermeasure against the lethal effects of radiation exposure. PMID:24708888

  17. Practical applications of internal dose calculations

    SciTech Connect

    Carbaugh, E.H.

    1994-06-01

    Accurate estimates of intake magnitude and internal dose are the goal for any assessment of an actual intake of radioactivity. When only one datum is available on which to base estimates, the choices for internal dose assessment become straight-forward: apply the appropriate retention or excretion function, calculate the intake, and calculate the dose. The difficulty comes when multiple data and different types of data become available. Then practical decisions must be made on how to interpret conflicting data, or how to adjust the assumptions and techniques underlying internal dose assessments to give results consistent with the data. This article describes nine types of adjustments which can be incorporated into calculations of intake and internal dose, and then offers several practical insights to dealing with some real-world internal dose puzzles.

  18. Toll-Like Receptor 2- and 6-Mediated Stimulation by Macrophage-Activating Lipopeptide 2 Induces Lipopolysaccharide (LPS) Cross Tolerance in Mice, Which Results in Protection from Tumor Necrosis Factor Alpha but in Only Partial Protection from Lethal LPS Doses

    PubMed Central

    Deiters, Ursula; Gumenscheimer, Marina; Galanos, Chris; Mühlradt, Peter F.

    2003-01-01

    Patients or experimental animals previously exposed to lipopolysaccharide (LPS) become tolerant to further LPS challenge. We investigated the potential of the macrophage-activating lipopeptide 2 (MALP-2) to induce in vivo cross tolerance to tumor necrosis factor alpha (TNF-α) and LPS. MALP-2-induced tolerance could be of practical interest, as MALP-2 proved much less pyrogenic in rabbits than LPS. Whereas LPS signals via Toll-like receptor 4 (TLR4), MALP-2 uses TLR2 and TLR6. LPS-mediated cytokine release was studied in mice pretreated with intraperitoneal injections of MALP-2. No biologically active TNF-α could be detected in the serum of MALP-2-treated animals when challenged with LPS 24 or 72 h later, whereas suppression of LPS-dependent interleukin (IL)-6 lasted for only 24 h. Protection from lethal TNF-α shock was studied in galactosamine-treated mice. Dose dependently, MALP-2 prevented death from lethal TNF-α doses in TLR4−/− but not in TLR2−/− mice, with protection lasting from 5 to 24 h. To assay protection from LPS, mice were pretreated with MALP-2 doses of up to 10 μg. Five and 24 h later, the animals were simultaneously sensitized and challenged by intravenous coinjection of galactosamine and a lethal dose of 50 ng of LPS. There was only limited protection (four of seven mice survived) when mice were challenged 5 h after MALP-2 pretreatment, and no protection when mice were challenged at later times. The high effectiveness of MALP-2 in suppressing TNF-α, the known ways of biological inactivation, and low pyrogenicity make MALP-2 a potential candidate for clinical use. PMID:12874325

  19. Application of non-lethal stable isotope analysis to assess feeding patterns of juvenile pallid sturgeon Scaphirhynchus albus: A comparison of tissue types and sample preservation methods

    USGS Publications Warehouse

    Andvik, R.T.; VanDeHey, J.A.; Fincel, M.J.; French, William E.; Bertrand, K.N.; Chipps, S.R.; Klumb, R.A.; Graeb, B.D.S.

    2010-01-01

    Traditional techniques for stable isotope analysis (SIA) generally require sacrificing animals to collect tissue samples; this can be problematic when studying diets of endangered species such as the pallid sturgeon Scaphirhynchus albus. Our objectives were to (i) determine if pectoral fin tissue (non-lethal) could be a substitute for muscle tissue (lethal) in SIA of juvenile pallid sturgeon, and (ii) evaluate the influence of preservation techniques on stable isotope values. In the laboratory, individual juvenile pallid sturgeon were held for up to 186 day and fed chironomids, fish, or a commercially available pellet diet. Significant, positive relationships (r2 ??? 0.8) were observed between fin and muscle tissues for both ??15N and ??13C; in all samples isotopes were enriched in fins compared to muscle tissue. Chironomid and fish based diets of juvenile pallid sturgeon were distinguishable for fast growing fish (0.3 mm day-1) using stable ??15N and ??13C isotopes. Frozen and preserved fin tissue ??15N isotopes were strongly related (r2 = 0.89) but ??13C isotopes were weakly related (r2 = 0.16). Therefore, freezing is recommended for preservation of fin clips to avoid the confounding effect of enrichment by ethanol. This study demonstrates the utility of a non-lethal technique to assess time integrated food habits of juvenile pallid sturgeon and should be applicable to other threatened or endangered species. ?? 2010 Blackwell Verlag, Berlin.

  20. Definition of lethality thresholds for KE less-lethal projectiles

    NASA Astrophysics Data System (ADS)

    Cuadros, Jaime H.

    1997-01-01

    The interest in the definition and application of the lethality threshold for KE less-lethal projectiles has increased in the last few years, as the demand for proper use of these weapons has increased from the public at large and the law enforcement community. Experiments have been performed and reported utilizing commercially available projectiles in 12 ga., 37 mm against an anthropomorphic dummy and damage criteria developed by the automobile industry. The utility of the method is discussed and future trends are presented.

  1. Development of an Orientia tsutsugamushi Lc-1 Murine Intraperitoneal Challenge Model for Scrub Typhus: Determination of Murine Lethal Dose (MuLD50), Tissue Bacterial Loads, and Clinical Outcomes.

    PubMed

    Lurchachaiwong, Woradee; McCardle, Wesley; Chan, Teik-Chye; Schuster, Anthony L; Richards, Allen L

    2015-09-01

    Currently, no vaccine has been developed to protect humans from naturally acquired heterologous Orientia tsutsugamushi infections. To enhance the validity of vaccine candidates, we are developing a murine chigger challenge model with the O. tsutsugamushi Lc-1-infected Leptotrombidium chiangraiensis Line-1. To this end, an intraperitoneal (i.p.) murine challenge model using an O. tsutsugamushi Lc-1 isolate was developed for eventual validation of the chigger challenge model. We have determined that the murine lethal dose that kills 50% of the challenged mice (MuLD50) of a liver/spleen homogenate developed from O. tsutsugamushi Lc-1-infected ICR Swiss mice to be 10(-6.9). Employing different inoculum doses of this homogenate, the bacterial load using quantitative real-time PCR (qPCR) was determined to range from 60 to 1.6 × 10(5) genome equivalent copies (GEC)/μL of liver and 33.4 to 2.2 × 10(5) GEC/μL of spleen tissue. The clinical outcomes relative to homogenate dose levels followed a dose-dependent pattern. The successful development and characterization of the O. tsutsugamushi Lc-1 i.p. challenge model will assist in the development and validation of a mouse chigger challenge scrub typhus model. PMID:26378973

  2. Improvements in extremity dose assessment for ionising radiation medical applications.

    PubMed

    Ginjaume, M; Pérez, S; Ortega, X

    2007-01-01

    This study aims at testing the INTE ring dosemeter based on MCP-Ns and TLD-100 detectors on users from the field of medical applications, namely radiopharmacists, personnel at a cyclotron facility with corresponding FDG synthesis cells, interventional radiology technologists and radiologists. These users were chosen due to the fact that they have a significantly high risk of exposure to their hands. Following previous results, MCP-Ns TL thin material was used for radiology measurements, whereas TLD-100 was preferred for other applications. The dosemeters were tested to make sure that they were waterproof and that they could be sterilised properly prior to use. Results confirm the need to implement finger dosimetry, mainly for interventional radiologists as finger dose can be >50 times higher than whole-body dose and 3 times higher than wrist dose. PMID:17277325

  3. Application of non-lethal stable isotope analysis to assess feeding patterns of juvenile pallid sturgeon Scaphirhynchus albus: a comparison of tissue types and sample preservation methods

    USGS Publications Warehouse

    Andvik, R.T.; VanDeHey, J.A.; Fincel, M.J.; French, William E.; Bertrand, K.N.; Chipps, Steven R.; Klumb, R.A.; Graeb, B.D.S.

    2010-01-01

    Traditional techniques for stable isotope analysis (SIA) generally require sacrificing animals to collect tissue samples; this can be problematic when studying diets of endangered species such as the pallid sturgeon Scaphirhynchus albus. Our objectives were to (i) determine if pectoral fin tissue (non-lethal) could be a substitute for muscle tissue (lethal) in SIA of juvenile pallid sturgeon, and (ii) evaluate the influence of preservation techniques on stable isotope values. In the laboratory, individual juvenile pallid sturgeon were held for up to 186 day and fed chironomids, fish, or a commercially available pellet diet. Significant, positive relationships (r² ≥ 0.8) were observed between fin and muscle tissues for both δ15N and δ13C; in all samples isotopes were enriched in fins compared to muscle tissue. Chironomid and fish based diets of juvenile pallid sturgeon were distinguishable for fast growing fish (0.3 mm day−1) using stable δ15N and δ13C isotopes. Frozen and preserved fin tissue δ15N isotopes were strongly related (r2 = 0.89) but δ13C isotopes were weakly related (r2 = 0.16). Therefore, freezing is recommended for preservation of fin clips to avoid the confounding effect of enrichment by ethanol. This study demonstrates the utility of a non-lethal technique to assess time integrated food habits of juvenile pallid sturgeon and should be applicable to other threatened or endangered species.

  4. Calculating Hematopoietic-Mode-Lethality Risk Avoidance Associated with Radionuclide Decorporation Countermeasures Related to a Radiological Terrorism Incident

    PubMed Central

    Scott, Bobby R.

    2009-01-01

    This paper provides theoretical health-risk-assessment tools that are designed to facilitate planning for and managing radiological terrorism incidents that involve ingestion exposure to bone-seeking radionuclides (e.g., radiostrontium nuclides). The focus is on evaluating lethality risk avoidance (RAV; i.e., the decrease in risk) that is associated with radionuclide decorporation countermeasures employed to remove ingested bone-seeking beta and/or gamma-emitting radionuclides from the body. To illustrate the application of tools presented, hypothetical radiostrontium decorporation scenarios were considered that involved evaluating the hematopoietic-mode-lethality RAV. For evaluating the efficacy of specific decorporation countermeasures, the lethality risk avoidance proportion (RAP; which is the RAV divided by the total lethality risk in the absence of protective countermeasures) is introduced. The lethality RAP is expected to be a useful tool for designing optimal radionuclide decorporation schemes and for identifying green, yellow and red dose-rate zones. For the green zone, essentially all of the lethality risk is expected to be avoided (RAP = 1) as a consequence of the radionuclide decorporation scheme used. For the yellow zone, some but not all of the lethality risk is expected to be avoided. For the red zone, none of the lethality risk (which equals 1) is expected to be avoided. PMID:20011652

  5. Prediction of protein-peptide interactions: application of the XPairIt API to anthrax lethal factor and substrates

    NASA Astrophysics Data System (ADS)

    Hurley, Margaret M.; Sellers, Michael S.

    2013-05-01

    As software and methodology develop, key aspects of molecular interactions such as detailed energetics and flexibility are continuously better represented in docking simulations. In the latest iteration of the XPairIt API and Docking Protocol, we perform a blind dock of a peptide into the cleavage site of the Anthrax lethal factor (LF) metalloprotein. Molecular structures are prepared from RCSB:1JKY and we demonstrate a reasonably accurate docked peptide through analysis of protein motion and, using NCI Plot, visualize and characterize the forces leading to binding. We compare our docked structure to the 1JKY crystal structure and the more recent 1PWV structure, and discuss both captured and overlooked interactions. Our results offer a more detailed look at secondary contact and show that both van der Waals and electrostatic interactions from peptide residues further from the enzyme's catalytic site are significant.

  6. A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection

    PubMed Central

    2014-01-01

    As the Ebola outbreak in West Africa continues and cases appear in the United States and other countries, the need for long-lasting vaccines to preserve global health is imminent. Here, we evaluate the long-term efficacy of a respiratory and sublingual (SL) adenovirus-based vaccine in non-human primates in two phases. In the first, a single respiratory dose of 1.4 × 109 infectious virus particles (ivp)/kg of Ad-CAGoptZGP induced strong Ebola glycoprotein (GP) specific CD8+ and CD4+ T cell responses and Ebola GP-specific antibodies in systemic and mucosal compartments and was partially (67%) protective from challenge 62 days after immunization. The same dose given by the SL route induced Ebola GP-specific CD8+ T cell responses similar to that of intramuscular (IM) injection, however, the Ebola GP-specific antibody response was low. All primates succumbed to infection. Three primates were then given the vaccine in a formulation that improved the immune response to Ebola in rodents. Three primates were immunized with 2.0 × 1010 ivp/kg of vaccine by the SL route. Diverse populations of polyfunctional Ebola GP-specific CD4+ and CD8+ T cells and significant anti-Ebola GP antibodies were present in samples collected 150 days after respiratory immunization. The formulated vaccine was fully protective against challenge 21 weeks after immunization. While diverse populations of Ebola GP-specific CD4+ T cells were produced after SL immunization, antibodies were not neutralizing and the vaccine was unprotective. To our knowledge, this is the first time that durable protection from a single dose respiratory adenovirus-based Ebola vaccine has been demonstrated in primates. PMID:25363619

  7. A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.

    PubMed

    Choi, Jin Huk; Jonsson-Schmunk, Kristina; Qiu, Xiangguo; Shedlock, Devon J; Strong, Jim; Xu, Jason X; Michie, Kelly L; Audet, Jonathan; Fernando, Lisa; Myers, Mark J; Weiner, David; Bajrovic, Irnela; Tran, Lilian Q; Wong, Gary; Bello, Alexander; Kobinger, Gary P; Schafer, Stephen C; Croyle, Maria A

    2015-08-01

    As the Ebola outbreak in West Africa continues and cases appear in the United States and other countries, the need for long-lasting vaccines to preserve global health is imminent. Here, we evaluate the long-term efficacy of a respiratory and sublingual (SL) adenovirus-based vaccine in non-human primates in two phases. In the first, a single respiratory dose of 1.4×10(9) infectious virus particles (ivp)/kg of Ad-CAGoptZGP induced strong Ebola glycoprotein (GP) specific CD8+ and CD4+ T cell responses and Ebola GP-specific antibodies in systemic and mucosal compartments and was partially (67%) protective from challenge 62 days after immunization. The same dose given by the SL route induced Ebola GP-specific CD8+ T cell responses similar to that of intramuscular (IM) injection, however, the Ebola GP-specific antibody response was low. All primates succumbed to infection. Three primates were then given the vaccine in a formulation that improved the immune response to Ebola in rodents. Three primates were immunized with 2.0×10(10) ivp/kg of vaccine by the SL route. Diverse populations of polyfunctional Ebola GP-specific CD4+ and CD8+ T cells and significant anti-Ebola GP antibodies were present in samples collected 150 days after respiratory immunization. The formulated vaccine was fully protective against challenge 21 weeks after immunization. While diverse populations of Ebola GP-specific CD4+ T cells were produced after SL immunization, antibodies were not neutralizing and the vaccine was unprotective. To our knowledge, this is the first time that durable protection from a single dose respiratory adenovirus-based Ebola vaccine has been demonstrated in primates. PMID:25363619

  8. AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation

    SciTech Connect

    Morita, Akinori; Ariyasu, Shinya; Wang, Bing; Asanuma, Tetsuo; Onoda, Takayoshi; Sawa, Akiko; Tanaka, Kaoru; Takahashi, Ippei; Togami, Shotaro; Nenoi, Mitsuru; Inaba, Toshiya; Aoki, Shin

    2014-08-08

    Highlights: • A bidentate HQ derivative, AS-2, suppresses p53-dependent apoptosis by DNA damage. • AS-2 does not significantly affect nuclear p53 response. • UV-excited blue emission of AS-2 clearly showed its extranuclear localization. • AS-2 prevents mitochondrial dysfunction despite the increase of mitochondrial p53. • AS-2 protects mice from a radiation dose that causes lethal hematopoietic syndrome. - Abstract: In a previous study, we reported that some tetradentate zinc(II) chelators inhibit p53 through the denaturation of its zinc-requiring structure but a chelator, Bispicen, a potent inhibitor of in vitro apoptosis, failed to show any efficient radioprotective effect against irradiated mice because the toxicity of the chelator to mice. The unsuitability of using tetradentate chelators as radioprotectors prompted us to undertake a more extensive search for p53-inhibiting agents that are weaker zinc(II) chelators and therefore less toxic. Here, we show that an 8-hydroxyquinoline (8HQ) derivative, AS-2, suppresses p53-dependent apoptosis through a transcription-independent mechanism. A mechanistic study using cells with different p53 characteristics revealed that the suppressive effect of AS-2 on apoptosis is specifically mediated through p53. In addition, AS-2 was less effective in preventing p53-mediated transcription-dependent events than pifithrin-μ (PFTμ), an inhibitor of transcription-independent apoptosis by p53. Fluorescence visualization of the extranuclear distribution of AS-2 also supports that it is ineffective on the transcription-dependent pathway. Further investigations revealed that AS-2 suppressed mitochondrial apoptotic events, such as the mitochondrial release of intermembrane proteins and the loss of mitochondrial membrane potential, although AS-2 resulted in an increase in the mitochondrial translocation of p53 as opposed to the decrease of cytosolic p53, and did not affect the apoptotic interaction of p53 with Bcl-2. AS-2 also

  9. A Single Intranasal Inoculation with a Paramyxovirus-Vectored Vaccine Protects Guinea Pigs against a Lethal-Dose Ebola Virus Challenge

    PubMed Central

    Bukreyev, Alexander; Yang, Lijuan; Zaki, Sherif R.; Shieh, Wun-Ju; Rollin, Pierre E.; Murphy, Brian R.; Collins, Peter L.; Sanchez, Anthony

    2006-01-01

    To determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against Ebola virus (EV), recombinant human parainfluenza virus type 3 (HPIV3) was modified to express either the EV structural glycoprotein (GP) by itself (HPIV3/EboGP) or together with the EV nucleoprotein (NP) (HPIV3/EboGP-NP). Expression of EV GP by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in Vero cells. HPIV3/EboGP was 100-fold more efficiently neutralized by antibodies to EV than by antibodies to HPIV3. Guinea pigs infected with a single intranasal inoculation of 105.3 PFU of HPIV3/EboGP or HPIV3/EboGP-NP showed no apparent signs of disease yet developed a strong humoral response specific to the EV proteins. When these animals were challenged with an intraperitoneal injection of 103 PFU of EV, there were no outward signs of disease, no viremia or detectable EV antigen in the blood, and no evidence of infection in the spleen, liver, and lungs. In contrast, all of the control animals died or developed severe EV disease following challenge. The highly effective immunity achieved with a single vaccine dose suggests that intranasal immunization with live vectored vaccines based on recombinant respiratory viruses may be an advantageous approach to inducing protective responses against severe systemic infections, such as those caused by hemorrhagic fever agents. PMID:16474134

  10. Analysis of cell cycle regulated and regulating proteins following exposure of lung derived cells to sub-lethal doses of a-rays

    NASA Astrophysics Data System (ADS)

    Trani, D.; Claudio, P. P.; Cassone, M.; Lucchetti, C.; D'Agostino, L.; Caputi, M.; Giordano, A.

    Introduction Since the last century mankind had to face an increased exposure to man made and natural sources of radiation Radiation represents a therapeutic instrument for radiosensitive cancers as well as a cytotoxic agent for normal human tissues The effects of prolonged exposure to low doses of high energy radiation are still not well-known at the molecular and clinical level Understanding their molecular effects will aid in developing more tailored therapeutic strategies as well as implementing radio-protective measures essential prerequisite for the long-time permanence of men in space Objective of the study The general aim of this study was to evaluate the susceptibility and the response of lung epithelial cells to DNA damage induced by ionizing radiations We decided to study a panel of epithelial bronchial cell lines because of their fast-growth rate and their prominent exposure to both environmental and medical radiations The specific objective of our study was to qualitatively and semi-quantitatively assess the involvement and behaviour of selected genes in DNA damage DNA-repair mechanisms and apoptosis which follow radiation exposure with the aim to determine the involvement of the most promising targets for the early detection of radiation-mediated lung damage before chronic disease develops Methods Four epithelial cell lines one normal and three neoplastic were selected in order to detect and compare survival cell cycle and protein expression differences related to their different genetic asset

  11. Assessment of Toxicity, Antifeedant Activity, and Biochemical Responses in Stored-Grain Insects Exposed to Lethal and Sublethal Doses of Gaultheria procumbens L. Essential Oil.

    PubMed

    Kiran, S; Prakash, Bhanu

    2015-12-01

    The present study was undertaken to investigate the insecticidal activity of chemically characterized Gaultheria procumbens essential oil (EO) and its mode of action against the Coleopteran insects Sitophilus oryzae and Rhyzopertha dominica. Gas chromatography-mass spectrometry results depicted methyl salicylate (MS) as the major compound (96.61%) of EO. EO and its major compound methyl salicylate (MS) showed 100% mortality at 150 and 5.0 μL/L air against S. oryzae and R. dominica, respectively, on 24 h of exposure. The in vivo percent inhibition of AChE activity ranged between 6.12 and 27.50%. In addition, changes in the antioxidative defense system, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and oxidized glutathione (GSSG), in test insects were estimated. A significant dose-dependent response in all test parameters was observed. The results demonstrated that G. procumbens EO could play a significant role in the formulation of EO-based insecticides for the management of stored-grain insects. PMID:26558484

  12. Dose Distribution Calculation in Skin Cancer Treatment Using Leipzig Applicator

    NASA Astrophysics Data System (ADS)

    Mowlawi, Ali Asghar; Yazdani, Majed

    The combination of 192Ir seed with the Leipzig applicators is used in a considerable number of clinical trials for skin cancer treatment. As is known, the beneficial effects of ionizing radiation for tumor treatment depends on the dosimetry accuracy. Nowadays, dosimetry calculations are supported by the characteristics provided by the manufacturer, which have been obtained from measurements with an ionization chamber in a phantom. Despite their benefit, the experimental data involves errors related to the positioning, energy, and angular dependence of the detectors. Thus, in order to get a detailed and more accurate dosimetry, the Monte Carlo code MCNP4C2 — Monte Carlo Neutron Particle, 4C2 version — has been employed to analyze the dose distribution in depth and at the surface in the skin cancer treatment using Leipzig applicators. On the other hand, some different measurements have been taken to validate the method and compare results. The results for this material of phantom (the skin with 0.5 cm thick over infinite soft tissue) can be used in treatment planning systems and also for computation of model dependent parameters like anisotropy dose function.

  13. Dose-Rate Dependence of High-Dose Health Effects in Humans from Photon Radiation with Application to Radiological Terrorism

    SciTech Connect

    Strom, Daniel J.

    2005-01-14

    In 1981, as part of a symposium entitled ''The Control of Exposure of the Public to Ionizing Radiation in the Event of Accident or Attack,'' Lushbaugh, H?bner, and Fry published a paper examining ''radiation tolerance'' of various human health endpoints as a function of dose rate. This paper may not have received the notice it warrants. The health endpoints examined by Lushbaugh et al. were the lethal dose that will kill 50% of people within 60 days of exposure without medical care (LD50/60); severe bone marrow damage in healthy men; severe bone marrow damage in leukemia patients; temporary sterility (azoospermia); reduced male fertility; and late effects such as cancer. Their analysis was grounded in extensive clinical experience and anchored to a few selected data points, and based on the 1968 dose-rate dependence theory of J.L. Bateman. The Lushbaugh et al. paper did not give predictive equations for the relationships, although they were implied in the text, and the relationships were presented in a non-intuitive way. This work derives the parameters needed in Bateman's equation for each health endpoint, tabulates the results, and plots them in a more conventional manner on logarithmic scales. The results give a quantitative indication of how the human organism can tolerate more radiation dose when it is delivered at lower dose rates. For example, the LD50/60 increases from about 3 grays (300 rads) when given at very high dose rates to over 10 grays (1,000 rads) when given at much lower dose rates over periods of several months. The latter figure is borne out by the case of an individual who survived for at least 19 years after receiving doses in the range of 9 to 17 grays (900-1700 rads) over 106 days. The Lushbaugh et al. work shows the importance of sheltering when confronted with long-term exposure to radiological contamination such as would be expected from a radiological dispersion event, reactor accident, or ground-level nuclear explosion.

  14. AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation.

    PubMed

    Morita, Akinori; Ariyasu, Shinya; Wang, Bing; Asanuma, Tetsuo; Onoda, Takayoshi; Sawa, Akiko; Tanaka, Kaoru; Takahashi, Ippei; Togami, Shotaro; Nenoi, Mitsuru; Inaba, Toshiya; Aoki, Shin

    2014-08-01

    In a previous study, we reported that some tetradentate zinc(II) chelators inhibit p53 through the denaturation of its zinc-requiring structure but a chelator, Bispicen, a potent inhibitor of in vitro apoptosis, failed to show any efficient radioprotective effect against irradiated mice because the toxicity of the chelator to mice. The unsuitability of using tetradentate chelators as radioprotectors prompted us to undertake a more extensive search for p53-inhibiting agents that are weaker zinc(II) chelators and therefore less toxic. Here, we show that an 8-hydroxyquinoline (8HQ) derivative, AS-2, suppresses p53-dependent apoptosis through a transcription-independent mechanism. A mechanistic study using cells with different p53 characteristics revealed that the suppressive effect of AS-2 on apoptosis is specifically mediated through p53. In addition, AS-2 was less effective in preventing p53-mediated transcription-dependent events than pifithrin-μ (PFTμ), an inhibitor of transcription-independent apoptosis by p53. Fluorescence visualization of the extranuclear distribution of AS-2 also supports that it is ineffective on the transcription-dependent pathway. Further investigations revealed that AS-2 suppressed mitochondrial apoptotic events, such as the mitochondrial release of intermembrane proteins and the loss of mitochondrial membrane potential, although AS-2 resulted in an increase in the mitochondrial translocation of p53 as opposed to the decrease of cytosolic p53, and did not affect the apoptotic interaction of p53 with Bcl-2. AS-2 also protected mice that had been exposed to a lethal dose of ionizing radiation. Our findings indicate that some types of bidentate 8HQ chelators could serve as radioprotectors with no substantial toxicity in vivo. PMID:25026551

  15. HDRMC, an accelerated Monte Carlo dose calculator for high dose rate brachytherapy with CT-compatible applicators

    SciTech Connect

    Chibani, Omar C-M Ma, Charlie

    2014-05-15

    Purpose: To present a new accelerated Monte Carlo code for CT-based dose calculations in high dose rate (HDR) brachytherapy. The new code (HDRMC) accounts for both tissue and nontissue heterogeneities (applicator and contrast medium). Methods: HDRMC uses a fast ray-tracing technique and detailed physics algorithms to transport photons through a 3D mesh of voxels representing the patient anatomy with applicator and contrast medium included. A precalculated phase space file for the{sup 192}Ir source is used as source term. HDRM is calibrated to calculated absolute dose for real plans. A postprocessing technique is used to include the exact density and composition of nontissue heterogeneities in the 3D phantom. Dwell positions and angular orientations of the source are reconstructed using data from the treatment planning system (TPS). Structure contours are also imported from the TPS to recalculate dose-volume histograms. Results: HDRMC was first benchmarked against the MCNP5 code for a single source in homogenous water and for a loaded gynecologic applicator in water. The accuracy of the voxel-based applicator model used in HDRMC was also verified by comparing 3D dose distributions and dose-volume parameters obtained using 1-mm{sup 3} versus 2-mm{sup 3} phantom resolutions. HDRMC can calculate the 3D dose distribution for a typical HDR cervix case with 2-mm resolution in 5 min on a single CPU. Examples of heterogeneity effects for two clinical cases (cervix and esophagus) were demonstrated using HDRMC. The neglect of tissue heterogeneity for the esophageal case leads to the overestimate of CTV D90, CTV D100, and spinal cord maximum dose by 3.2%, 3.9%, and 3.6%, respectively. Conclusions: A fast Monte Carlo code for CT-based dose calculations which does not require a prebuilt applicator model is developed for those HDR brachytherapy treatments that use CT-compatible applicators. Tissue and nontissue heterogeneities should be taken into account in modern HDR

  16. Lethal and Sub-lethal Effects of UVB on Juvenile Biomphalaria glabrata (Mollusca: Pulmonata)

    PubMed Central

    Ruelas, Debbie S.; Karentz, Deneb; Sullivan, John T.

    2007-01-01

    Although Schistosoma mansoni occurs mainly in the tropics, where intense levels of solar radiation are present, the impact of ultraviolet (UV) light on schistosome transmission is not known. The purpose of this study was to investigate potential effects of UVB (290–320 nm) on juvenile Biomphalaria glabrata, the snail intermediate host of S. mansoni. Albino and wild type snails were exposed to doses of UVB from UV-fluorescent lamps, and the following were measured: survival, photoreactivation (light-mediated DNA repair), effects on feeding behavior, and morphological tissue abnormalities. Irradiation with UVB is lethal to B. glabrata in a dose-dependent manner. Exposure to white light subsequent to UVB irradiation enhances survival, probably by photoreactivation. The shell offers some, but not complete, protection. Experiments in which UVB transmittance through the shell was blocked with black nail polish suggest that injury to both exposed (headfoot) and shell-enclosed (mantle and visceral mass) tissues contributes to mortality in lethally-irradiated snails. Wild-type (pigmented) snails are less susceptible to lethal effects of UVB than albino snails, and they may be more capable of photoreactivation. UVB exposure inhibits snail feeding behavior, and causes tentacle forks and growths on the headfoot. Thus, UVB may influence the life cycle of S. mansoni by both lethal and sub-lethal damage to the snail intermediate host. However, the ability of snails to photoreactivate may mitigate these effects. PMID:16996081

  17. In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion protein fully protected mice against lethal dose of H1, H3 and H9 influenza A isolates circulating in Iran

    SciTech Connect

    Ebrahimi, Seyyed Mahmoud; Dabaghian, Mehran; Tebianian, Majid

    2012-08-15

    Ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuvants or complex formulations. Hence, recombinant fusion protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats of the ectodomain of the conserved influenza matrix protein M2 (M2e) was expressed in Escherichia coli, purified under denaturing condition, refolding, and then confirmed by SDS-PAGE, respectively. The recombinant fusion protein, 4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A isolates from Iran compared to 0-33.34% survival rate of challenged unimmunized and immunized mice with the currently in use conventional vaccines designated as control groups. However, protection induced by immunization with 4xM2e.HSP70c failed to prevent weight loss in challenged mice; they experienced significantly lower weight loss, clinical symptoms and higher lung viral clearance in comparison with protective effects of conventional influenza vaccines in challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a superior candidate to deliver the adjuvant function in M2e-based influenza A vaccine in order to provide significant protection against multiple influenza A virus strains.

  18. Application of MCNP{trademark} to storage facility dose rate assessment

    SciTech Connect

    Urban, W.T.; Roberts, R.R.; Estes, G.P.; Taylor, W.M.

    1996-12-31

    The MCNP code is widely used in the determination of neutral particle dose rate analyses. In this paper we examine the application of MCNP to several storage facilities containing special nuclear material, SNM, wherein the neutron dose rate is the primary quantity of interest. In particular, we describe the special geometry, modeling assumptions, and physics considerations encountered in each of three applications.

  19. Dosimetric optimization of a conical breast brachytherapy applicator for improved skin dose sparing

    SciTech Connect

    Yang Yun; Rivard, Mark J.

    2010-11-15

    Purpose: Both the AccuBoost D-shaped and round applicators have been dosimetrically characterized and clinically used to treat patients with breast cancer. While the round applicators provide conformal dose coverage, under certain clinical circumstances the breast skin dose may be higher than preferred. The purpose of this study was to modify the round applicators to minimize skin dose while not substantially affecting dose uniformity within the target volume and reducing the treatment time. Methods: In order to irradiate the intended volume while sparing critical structures such as the skin, the current round applicator design has been augmented through the addition of an internal truncated cone (i.e., frustum) shield. Monte Carlo methods and clinical constraints were used to design the optimal cone applicator. With the cone applicator now defined as the entire assembly including the surrounding tungsten-alloy shell holding the HDR {sup 192}Ir source catheter, the applicator height was reduced to diminish the treatment time while minimizing skin dose. Monte Carlo simulation results were validated using both radiochromic film and ionization chamber measurements based on established techniques. Results: The optimal cone applicators diminished the maximum skin dose by 15%-32% (based on the applicator diameter and breast separation) with the tumor dose reduced by less than 3% for a constant exposure time. Furthermore, reduction in applicator height diminished the treatment time by up to 30%. Radiochromic film and ionization chamber dosimetric results in phantom agreed with Monte Carlo simulation results typically within 3%. Larger differences were outside the treatment volume in low dose regions or associated with differences between the measurement and Monte Carlo simulation environments. Conclusions: A new radiotherapy treatment device was developed and dosimetrically characterized. This set of applicators significantly reduces the skin dose and treatment time while

  20. Application of a sitting MIRD phantom for effective dose calculations.

    PubMed

    Olsher, Richard H; Van Riper, Kenneth A

    2005-01-01

    In typical realistic scenarios, dose factors due to 60Co contaminated steel, used in consumer products, cannot be approximated by standard exposure geometries. It is then necessary to calculate the effective dose using an appropriate anthropomorphic phantom. MCNP calculations were performed using a MIRD human model in two settings. In the first, a male office worker is sitting in a chair containing contaminated steel, surrounded by contaminated furniture. In the second, a male driver is seated inside an automobile, the steel of which is uniformly contaminated. To accurately calculate the dose to lower body organs, especially the gonads, it was essential to modify the MIRD model to simulate two sitting postures: chair and driving position. The phantom modifications are described, and the results of the calculations are presented. In the case of the automobile scenarios, results are compared to those obtained using an isotropic fluence-to-dose conversion function. PMID:16604666

  1. In vitro breast cancer cell lethality of Brazilian plant extracts.

    PubMed

    Suffredini, I B; Paciencia, M L B; Frana, S A; Varella, A D; Younes, R N

    2007-10-01

    In this study we screened the cytotoxicity of 1220 plant extracts obtained from 351 plants belonging to 74 families occurring in the Amazon and Atlantic rain forests against MCF-7 human breast adenocarcinoma cell lines. All extracts were tested at a dose of 100 microg/mL. Only 11 aqueous or organic extracts belonging to the Annonaceae, Apocynaceae, Araceae, Clusiaceae, Flacourtiaceae, Leguminosae, Olacaceae and Violaceae showed marked lethal activity. Vismia guianensis and Annona hypoglauca extracts showed the greatest lethal activity. PMID:18236788

  2. Accurate skin dose measurements using radiochromic film in clinical applications

    SciTech Connect

    Devic, S.; Seuntjens, J.; Abdel-Rahman, W.; Evans, M.; Olivares, M.; Podgorsak, E.B.; Vuong, Te; Soares, Christopher G.

    2006-04-15

    Megavoltage x-ray beams exhibit the well-known phenomena of dose buildup within the first few millimeters of the incident phantom surface, or the skin. Results of the surface dose measurements, however, depend vastly on the measurement technique employed. Our goal in this study was to determine a correction procedure in order to obtain an accurate skin dose estimate at the clinically relevant depth based on radiochromic film measurements. To illustrate this correction, we have used as a reference point a depth of 70 {mu}. We used the new GAFCHROMIC[reg] dosimetry films (HS, XR-T, and EBT) that have effective points of measurement at depths slightly larger than 70 {mu}. In addition to films, we also used an Attix parallel-plate chamber and a home-built extrapolation chamber to cover tissue-equivalent depths in the range from 4 {mu} to 1 mm of water-equivalent depth. Our measurements suggest that within the first millimeter of the skin region, the PDD for a 6 MV photon beam and field size of 10x10 cm{sup 2} increases from 14% to 43%. For the three GAFCHROMIC[reg] dosimetry film models, the 6 MV beam entrance skin dose measurement corrections due to their effective point of measurement are as follows: 15% for the EBT, 15% for the HS, and 16% for the XR-T model GAFCHROMIC[reg] films. The correction factors for the exit skin dose due to the build-down region are negligible. There is a small field size dependence for the entrance skin dose correction factor when using the EBT GAFCHROMIC[reg] film model. Finally, a procedure that uses EBT model GAFCHROMIC[reg] film for an accurate measurement of the skin dose in a parallel-opposed pair 6 MV photon beam arrangement is described.

  3. Dose Modification Factor Analysis of Multi-Lumen Brachytherapy Applicator with Monte Carlo Simulation

    NASA Astrophysics Data System (ADS)

    Williams, Eric Alan

    Multi-lumen applicators like the Contura (SenoRx, Inc.) are used in partial breast irradiation (PBI) brachytherapy in instances where asymmetric dose distributions are desired, for example, when the applicator surface-to-skin thickness is small (<7mm). In these instances, the air outside the patient and the lung act as a poor scattering medium, scattering less dose back into the breast tissue which affects the dose distribution. Many commercial treatment planning systems do not correct for tissue heterogeneity, which results in inaccuracies in the planned dose distribution. This deviation has been quantified as the dose modification factor (DMF), equal to the ratio of the dose rate at 1cm beyond the applicator surface, with homogenous medium, to the dose rate at 1cm with heterogeneous medium. This investigation intends to model the Contura applicator with the Monte Carlo N-Particle code (MCNP, Los Alamos National Labs), determine a DMF through simulation, and correlate to previous measurements. Taking all geometrical considerations into account, an accurate model of the Contura balloon applicator was created in MCNP. This model was used to run simulations of symmetric and asymmetric plans. The dose modification factor was found to be dependent on the simulated water phantom geometry, with cuboid geometry yielding a max DMF of 1.0664. The same measurements taken using a spherical geometry water phantom gave a DMF of 1.1221. It was also seen that the difference in DMF between symmetric and asymmetric plans using the Contura applicator is minimal.

  4. A broadly applicable function for describing luminescence dose response

    SciTech Connect

    Burbidge, C. I.

    2015-07-28

    The basic form of luminescence dose response is investigated, with the aim of developing a single function to account for the appearance of linear, superlinear, sublinear, and supralinear behaviors and variations in saturation signal level and rate. A function is assembled based on the assumption of first order behavior in different major factors contributing to measured luminescence-dosimetric signals. Different versions of the function are developed for standardized and non-dose-normalized responses. Data generated using a two trap two recombination center model and experimental data for natural quartz are analyzed to compare results obtained using different signals, measurement protocols, pretreatment conditions, and radiation qualities. The function well describes a range of dose dependent behavior, including sublinear, superlinear, supralinear, and non-monotonic responses and relative response to α and β radiation, based on change in relative recombination and trapping probability affecting signals sourced from a single electron trap.

  5. A broadly applicable function for describing luminescence dose response

    NASA Astrophysics Data System (ADS)

    Burbidge, C. I.

    2015-07-01

    The basic form of luminescence dose response is investigated, with the aim of developing a single function to account for the appearance of linear, superlinear, sublinear, and supralinear behaviors and variations in saturation signal level and rate. A function is assembled based on the assumption of first order behavior in different major factors contributing to measured luminescence-dosimetric signals. Different versions of the function are developed for standardized and non-dose-normalized responses. Data generated using a two trap two recombination center model and experimental data for natural quartz are analyzed to compare results obtained using different signals, measurement protocols, pretreatment conditions, and radiation qualities. The function well describes a range of dose dependent behavior, including sublinear, superlinear, supralinear, and non-monotonic responses and relative response to α and β radiation, based on change in relative recombination and trapping probability affecting signals sourced from a single electron trap.

  6. Lethality test system

    SciTech Connect

    Parsons, W.M.; Sims, J.R.; Parker, J.V.

    1986-01-01

    The Lethality Test System (LTS), presently under construction at Los Alamos, is an electromagnetic launcher facility designed to perform impact experiments at velocities up to 15 km/s. The launcher is a 25 mm round bore, plasma armature railgun extending 22 m in length. Preinjection is accomplished with a two-stage gas gun capable of 7 km/s. The railgun power supply utilizes traction motors, vacuum interrupters, and pulse transformers. An assembly of 28 traction motors, equipped with flywheels, stores approximately 80 MJ at 92% of full speed and energizes the primary windings of three pulse transformers at a current of 50 kA. At peak current an array of vacuum interrupters disconnects the transformer primary windings and forces the current to flow in the secondary windings. The secondary windings are connected to the railgun, and by staging the vacuum interrupter openings, a 1 MA to 1.3 MA ramped current waveform will be delivered to the railgun.

  7. The Lethality Test System

    NASA Astrophysics Data System (ADS)

    Parsons, W. M.; Sims, J. R.; Parker, J. V.

    1986-11-01

    The Lethality Test System (LTS) under construction at Los Alamos is an electromagnetic launcher facility designed to perform impact experiments at velocities up to 15 km/sec. The launcher is a 25 mm round bore, plasma armature railgun 22 m in length. Preinjection is accomplished with a two-stage light gas gun capable of 7 km/sec. The railgun power supply utilizes traction motors, vacuum interrupters, and pulse transformers. An assembly of 28 traction motors, equipped with flywheels, stores approximately 80 MJ at 92 percent of full speed and energizes the primary windings of three pulse transformers at a current of 50 kA. At peak current an array of vacuum interrupters disconnects the transformer primary windings and forces the current to flow in the secondary windings. The secondary windings are connected to the railgun, and by staging the vacuum interrupter openings, a 1-1.3 MA ramped current waveform will be delivered to the railgun.

  8. HDR Brachytherapy Dose Distribution is Influenced by the Metal Material of the Applicator

    PubMed Central

    Wu, Chin-Hui; Liao, Yi-Jen; Shiau, An-Cheng; Lin, Hsin-Yu; Hsueh Liu, Yen-Wan; Hsu, Shih-Ming

    2015-01-01

    Applicators containing metal have been widely used in recent years when applying brachytherapy to patients with cervical cancer. However, the high dose rate (HDR) treatment-planning system (TPS) that is currently used in brachytherapy still assumes that the treatment environment constitutes a homogeneous water medium and does not include a dose correction for the metal material of the applicator. The primary purpose of this study was to evaluate the HDR 192Ir dose distribution in cervical cancer patients when performing brachytherapy using a metal-containing applicator. Thermoluminescent dosimeter (TLD) measurements and Monte Carlo N-Particle eXtended (MCNPX) code were used to explore the doses to the rectum and bladder when using a Henschke applicator containing metal during brachytherapy. When the applicator was assumed to be present, the absolute dose difference between the TLD measurement and MCNPX simulation values was within approximately 5%. A comparison of the MCNPX simulation and TPS calculation values revealed that the TPS overestimated the International Commission of Radiation Units and Measurement (ICRU) rectum and bladder reference doses by 57.78% and 49.59%, respectively. We therefore suggest that the TPS should be modified to account for the shielding effects of the applicator to ensure the accuracy of the delivered doses. PMID:26658746

  9. HDR Brachytherapy Dose Distribution is Influenced by the Metal Material of the Applicator.

    PubMed

    Wu, Chin-Hui; Liao, Yi-Jen; Shiau, An-Cheng; Lin, Hsin-Yu; Hsueh Liu, Yen-Wan; Hsu, Shih-Ming

    2015-01-01

    Applicators containing metal have been widely used in recent years when applying brachytherapy to patients with cervical cancer. However, the high dose rate (HDR) treatment-planning system (TPS) that is currently used in brachytherapy still assumes that the treatment environment constitutes a homogeneous water medium and does not include a dose correction for the metal material of the applicator. The primary purpose of this study was to evaluate the HDR (192)Ir dose distribution in cervical cancer patients when performing brachytherapy using a metal-containing applicator. Thermoluminescent dosimeter (TLD) measurements and Monte Carlo N-Particle eXtended (MCNPX) code were used to explore the doses to the rectum and bladder when using a Henschke applicator containing metal during brachytherapy. When the applicator was assumed to be present, the absolute dose difference between the TLD measurement and MCNPX simulation values was within approximately 5%. A comparison of the MCNPX simulation and TPS calculation values revealed that the TPS overestimated the International Commission of Radiation Units and Measurement (ICRU) rectum and bladder reference doses by 57.78% and 49.59%, respectively. We therefore suggest that the TPS should be modified to account for the shielding effects of the applicator to ensure the accuracy of the delivered doses. PMID:26658746

  10. Application of Benchmark Dose Methodology to a Variety of Endpoints and Exposures

    EPA Science Inventory

    This latest beta version (1.1b) of the U.S. Environmental Protection Agency (EPA) Benchmark Dose Software (BMDS) is being distributed for public comment. The BMDS system is being developed as a tool to facilitate the application of benchmark dose (BMD) methods to EPA hazardous p...

  11. 28 CFR 552.25 - Use of chemical agents or non-lethal weapons.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Use of chemical agents or non-lethal... INSTITUTIONAL MANAGEMENT CUSTODY Use of Force and Application of Restraints on Inmates § 552.25 Use of chemical agents or non-lethal weapons. The Warden may authorize the use of chemical agents or non-lethal...

  12. Lethal mobilization of DDT by cowbirds

    USGS Publications Warehouse

    Van Velzen, A.C.; Stiles, W.B.; Stickel, L.F.

    1972-01-01

    This study is an experimental demonstration of lethal mobilization of DDT by brown-headed cowbirds (Molothrus ater) and the effects of food deprivation on the distribution and loss of DDT, DDD, and DDE. The principal experimental group consisted of 20 birds fed a dietary dosage of 100 ppm of DDT for 13 days. After 2 days of full rations of untreated food, they were subjected to food restriction. Food was reduced to 43 percent of normal. Seven of the 20 birds died within 4 days. No birds died in the three control groups, treated as follows: ( 1 ) 20 birds fed 100 ppm DDT for 13 days and full rations of untreated food thereafter, (2) 20 birds fed only untreated food but subjected to food restriction, and (3) 20 birds fed full rations of untreated food throughout. In a pilot study, birds were fed 100, 200, or 300 ppm of DDT and subjected to two periods of food restriction, the first of these immediately after dosage ceased and the second 4 months later. DDT-dosed birds from all dosage levels died in each period of food restriction. Before the weight loss that accompanied food restriction, the brains of DDT-dosed birds had concentrations of DDT and DDD that were far below the lethal range. Concentrations increased rapidly to lethal levels. In these birds, DDT in carcasses decreased while DDD increased. DDT-dosed birds that died during food restriction lost 16 percent of their total body burden of DDT + DDD + DDE, 21 percent of their weight, and 81 percent of their fat. The DDT-dosed birds that were subjected to food restriction but survived lost a significantly greater proportion of their body burden of residues than similarly dosed birds not subjected to weight loss. Brain levels of DDT and DDD in birds that died during food restriction soon after dosage did not differ significantly from brain levels of birds that died in a period of food restriction 4 months after dosage. Concentrations of DDE were significantly higher in the latter group, although they were lower

  13. Comparison of different dose reduction system in computed tomography for orthodontic applications

    PubMed Central

    FANUCCI, E.; FIASCHETTI, V.; OTTRIA, L.; MATALONI, M; ACAMPORA, V.; LIONE, R.; BARLATTANI, A.; SIMONETTI, G.

    2011-01-01

    SUMMARY To correlate different CT system: MSCT (multislice computed tomography) with different acquisition parameters (100KV, 80KV), different reconstruction algorithm (ASIR) and CBCT (cone beam computed tomography) examination in terms of absorbed X-ray dose and diagnostic accuracy. 80 KV protocols compared with 100 KV protocols resulted in reduced total radiation dose without relevant loss of diagnostic image information and quality. CBCT protocols compared with 80 KV MSCT protocols resulted in reduced total radiation dose but loss of diagnostic image information and quality although no so relevant. In addition the new system applies to equipment ASIR applicable on MSCT allows 50% of the dose without compromising image quality. PMID:23285397

  14. The repair of sub-lethal damage and the stimulated repair of potentially lethal damage in Saintpaulia.

    PubMed

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

    1981-10-01

    The repair of sublethal and potentially lethal damage in stationary resting epidermal cells of Saintpaulia has been investigated. Fractionation experiments reveal an efficient repair of sublethal damage with a half-life of 1.9 hours. No repair of potentially lethal damage was noted when cultivation of the leaves was delayed for 24 hours after irradiation. At delay times of 2, 3 and 4 days some repair of potentially lethal damage has been found. A small pre-dose given 24 hours before a challenging dose improved the cells' chance to regenerate and the improvement has been shown to be compatible with an improved repair of potentially lethal damage induced by X-rays and fast neutrons. It hs been shown that the stimulated repair process takes 12 to 24 hours to develop, is dependent on the size of the pre-dose, has single-hit dose kinetics, and an r.b.e. of 1 for neutrons. With delayed cultivation of 2 days the stimulated repair process leads to an alteration in the shape of the regeneration (survival)-dose relationship which increases the low dose r.b.e. for neutrons from 10 to 35. PMID:6975252

  15. Application of radiochromic gel detector (FXG) for UVA dose measurements

    NASA Astrophysics Data System (ADS)

    Abukassem, Issam; Bero, Mamdouh A.

    2010-12-01

    Tissue equivalent radiochromic gel material containing ferrous ions, xylenol-orange ion indicator and gelatin as gelling agent (FXG) is known to be sensitive to γ- and X-rays; hence it has been used for ionizing radiation dosimetry. Changes in optical absorbance properties of FXG material over a wide region in the visible spectrum were found to be proportional to the radiation absorbed dose. An earlier study demonstrated the sensitivity of FXG gel detector to ultraviolet radiation and therefore that could give quantitative measure for UV exposure. This study focuses on the detection of UVA radiation (315-400 nm), which forms an important part (˜97%) of the natural solar UV radiation reaching the earth surface. A solar UV simulator device was used to deliver UVA radiation to FXG samples. The beam was optically modified to irradiate gel samples at an exposure level about 58 W/m 2, which is comparable to the summer natural UVA radiation measured outside the laboratory building at midday (˜60 W/m 2). Experimental results were used to generate mathematical second order formulas that give the relationship between UVA dose and optical absorbance changes observed at two wavelengths in the visible region of the spectrum—430 and 560 nm.

  16. High-dose processing and application to Korean space foods

    NASA Astrophysics Data System (ADS)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-07-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods ( Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  17. The use of tetrahedral mesh geometries in Monte Carlo simulation of applicator based brachytherapy dose distributions.

    PubMed

    Fonseca, Gabriel Paiva; Landry, Guillaume; White, Shane; D'Amours, Michel; Yoriyaz, Hélio; Beaulieu, Luc; Reniers, Brigitte; Verhaegen, Frank

    2014-10-01

    Accounting for brachytherapy applicator attenuation is part of the recommendations from the recent report of AAPM Task Group 186. To do so, model based dose calculation algorithms require accurate modelling of the applicator geometry. This can be non-trivial in the case of irregularly shaped applicators such as the Fletcher Williamson gynaecological applicator or balloon applicators with possibly irregular shapes employed in accelerated partial breast irradiation (APBI) performed using electronic brachytherapy sources (EBS). While many of these applicators can be modelled using constructive solid geometry (CSG), the latter may be difficult and time-consuming. Alternatively, these complex geometries can be modelled using tessellated geometries such as tetrahedral meshes (mesh geometries (MG)). Recent versions of Monte Carlo (MC) codes Geant4 and MCNP6 allow for the use of MG. The goal of this work was to model a series of applicators relevant to brachytherapy using MG. Applicators designed for (192)Ir sources and 50 kV EBS were studied; a shielded vaginal applicator, a shielded Fletcher Williamson applicator and an APBI balloon applicator. All applicators were modelled in Geant4 and MCNP6 using MG and CSG for dose calculations. CSG derived dose distributions were considered as reference and used to validate MG models by comparing dose distribution ratios. In general agreement within 1% for the dose calculations was observed for all applicators between MG and CSG and between codes when considering volumes inside the 25% isodose surface. When compared to CSG, MG required longer computation times by a factor of at least 2 for MC simulations using the same code. MCNP6 calculation times were more than ten times shorter than Geant4 in some cases. In conclusion we presented methods allowing for high fidelity modelling with results equivalent to CSG. To the best of our knowledge MG offers the most accurate representation of an irregular APBI balloon applicator. PMID

  18. The use of tetrahedral mesh geometries in Monte Carlo simulation of applicator based brachytherapy dose distributions

    NASA Astrophysics Data System (ADS)

    Paiva Fonseca, Gabriel; Landry, Guillaume; White, Shane; D'Amours, Michel; Yoriyaz, Hélio; Beaulieu, Luc; Reniers, Brigitte; Verhaegen, Frank

    2014-10-01

    Accounting for brachytherapy applicator attenuation is part of the recommendations from the recent report of AAPM Task Group 186. To do so, model based dose calculation algorithms require accurate modelling of the applicator geometry. This can be non-trivial in the case of irregularly shaped applicators such as the Fletcher Williamson gynaecological applicator or balloon applicators with possibly irregular shapes employed in accelerated partial breast irradiation (APBI) performed using electronic brachytherapy sources (EBS). While many of these applicators can be modelled using constructive solid geometry (CSG), the latter may be difficult and time-consuming. Alternatively, these complex geometries can be modelled using tessellated geometries such as tetrahedral meshes (mesh geometries (MG)). Recent versions of Monte Carlo (MC) codes Geant4 and MCNP6 allow for the use of MG. The goal of this work was to model a series of applicators relevant to brachytherapy using MG. Applicators designed for 192Ir sources and 50 kV EBS were studied; a shielded vaginal applicator, a shielded Fletcher Williamson applicator and an APBI balloon applicator. All applicators were modelled in Geant4 and MCNP6 using MG and CSG for dose calculations. CSG derived dose distributions were considered as reference and used to validate MG models by comparing dose distribution ratios. In general agreement within 1% for the dose calculations was observed for all applicators between MG and CSG and between codes when considering volumes inside the 25% isodose surface. When compared to CSG, MG required longer computation times by a factor of at least 2 for MC simulations using the same code. MCNP6 calculation times were more than ten times shorter than Geant4 in some cases. In conclusion we presented methods allowing for high fidelity modelling with results equivalent to CSG. To the best of our knowledge MG offers the most accurate representation of an irregular APBI balloon applicator.

  19. Comparison of dose calculation algorithms for colorectal cancer brachytherapy treatment with a shielded applicator

    SciTech Connect

    Yan Xiangsheng; Poon, Emily; Reniers, Brigitte; Vuong, Te; Verhaegen, Frank

    2008-11-15

    Colorectal cancer patients are treated at our hospital with {sup 192}Ir high dose rate (HDR) brachytherapy using an applicator that allows the introduction of a lead or tungsten shielding rod to reduce the dose to healthy tissue. The clinical dose planning calculations are, however, currently performed without taking the shielding into account. To study the dose distributions in shielded cases, three techniques were employed. The first technique was to adapt a shielding algorithm which is part of the Nucletron PLATO HDR treatment planning system. The isodose pattern exhibited unexpected features but was found to be a reasonable approximation. The second technique employed a ray tracing algorithm that assigns a constant dose ratio with/without shielding behind the shielding along a radial line originating from the source. The dose calculation results were similar to the results from the first technique but with improved accuracy. The third and most accurate technique used a dose-matrix-superposition algorithm, based on Monte Carlo calculations. The results from the latter technique showed quantitatively that the dose to healthy tissue is reduced significantly in the presence of shielding. However, it was also found that the dose to the tumor may be affected by the presence of shielding; for about a quarter of the patients treated the volume covered by the 100% isodose lines was reduced by more than 5%, leading to potential tumor cold spots. Use of any of the three shielding algorithms results in improved dose estimates to healthy tissue and the tumor.

  20. Dosimetric characterizations of GZP6 60Co high dose rate brachytherapy sources: application of superimposition method

    PubMed Central

    Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Mowlavi, Ali Asghar; Meigooni, Ali Soleimani

    2012-01-01

    Background Dosimetric characteristics of a high dose rate (HDR) GZP6 Co-60 brachytherapy source have been evaluated following American Association of Physicists in MedicineTask Group 43U1 (AAPM TG-43U1) recommendations for their clinical applications. Materials and methods MCNP-4C and MCNPX Monte Carlo codes were utilized to calculate dose rate constant, two dimensional (2D) dose distribution, radial dose function and 2D anisotropy function of the source. These parameters of this source are compared with the available data for Ralstron 60Co and microSelectron192Ir sources. Besides, a superimposition method was developed to extend the obtained results for the GZP6 source No. 3 to other GZP6 sources. Results The simulated value for dose rate constant for GZP6 source was 1.104±0.03 cGyh-1U-1. The graphical and tabulated radial dose function and 2D anisotropy function of this source are presented here. The results of these investigations show that the dosimetric parameters of GZP6 source are comparable to those for the Ralstron source. While dose rate constant for the two 60Co sources are similar to that for the microSelectron192Ir source, there are differences between radial dose function and anisotropy functions. Radial dose function of the 192Ir source is less steep than both 60Co source models. In addition, the 60Co sources are showing more isotropic dose distribution than the 192Ir source. Conclusions The superimposition method is applicable to produce dose distributions for other source arrangements from the dose distribution of a single source. The calculated dosimetric quantities of this new source can be introduced as input data to the GZP6 treatment planning system (TPS) and to validate the performance of the TPS. PMID:23077455

  1. Serum amyloid A protects murine macrophages from lethal toxin-mediated death.

    PubMed

    Rose, Kira; Long, Paul; Shankar, Malini; Ballard, Jimmy D; Webb, Carol F

    2012-01-01

    Lethal toxin, a key virulence factor produced by Bacillus anthracis, induces cell death, in part by disrupting numerous signaling pathways, in mouse macrophages. However, exposure to sublethal doses of lethal toxin allows some cells to survive. Because these pro-survival signaling events occur within a few hours after exposure to sublethal doses, we hypothesized that acute phase proteins might influence macrophage survival. Our data show that serum amyloid A (SAA) is produced in response to lethal toxin treatment. Moreover, pre-treatment of macrophages with exogenous SAA protected macrophages from lethal toxin-mediated death. Exogenous SAA activated the p38 mitogen activated protein kinase (MAP) kinase pathway, while lethal toxin mutants incapable of p38 activation were incapable of causing cell death. Chemical inhibition of the p38 activation pathway abrogated the protective effects of SAA. These data show that SAA affords protection against lethal toxin in mouse macrophages and link this response to the p38 pathway. PMID:22082566

  2. Enhancement of X-ray dose absorption for medical applications

    NASA Astrophysics Data System (ADS)

    Lim, Sara; Montenegro, Maximiliano; Nahar, Sultana; Pradhan, Anil; Barth, Rolf; Nakkula, Robin; Bell, Erica; Yu, Yan

    2012-06-01

    Interaction of high-Z (HZ) elements with X-rays occurs efficiently at specific resonant energies. Cross sections for photoionization rapidly decrease after the K-edge; higher energy X-rays are mostly Compton-scattered. These features restrict the energy range for the use of HZ moities for radiosensitization in cancer therapy. Conventional X-ray sources such as linear accelerators (LINAC) used in radiotherapy emit a broad spectrum up to MeV energies. We explore the dichotomy between X-ray radiotherapy in two ranges: (i) E < 100 keV including HZ sensitization, and (ii) E > 100 keV where sensitization is inefficient. We perform Monte Carlo numerical simulations of tumor tissue embedded with platinum compounds and gold nanoparticles and compute radiation dose enhancement factors (DEF) upon irradiation with 100 kV, 170 kV and 6 MV sources. Our results demonstrate that the DEF peak below 100 keV and fall sharply above 200 keV to very small values. Therefore most of the X-ray output from LINACs up to the MeV range is utilized very inefficiently. We also describe experimental studies for implementation of option (i) using Pt and Au reagents and selected cancer cell lines. Resultant radiation exposure to patients could be greatly reduced, yet still result in increased tumoricidal ability.

  3. The application of high dose food irradiation in South Africa

    NASA Astrophysics Data System (ADS)

    de Bruyn, Ingrid Nine

    2000-03-01

    During the 1950s to the end of the 1970s the United States Army developed the basic methodology to produce shelf-stable irradiated meat, seafood and poultry products. These products are normally packed without gravy, sauce or brine, as liquid is not required to sterilize the product as in the canning process. This leads to the distinctive "dried cooked" taste normally associated with roasts opposed to the casserole taste usually associated with tinned meats. The Biogam group at the Atomic Energy Corporation of South Africa is currently producing shelf-stable irradiated meats on a commercial basis. The meats are cooked, chilled, portioned, vacuum packed and irradiated to the required minimum dose of 45 kGy at a temperature of between -20 and -40°C to ensure absolute sterility even under tropical conditions. The product is packaged in a high quality four layer laminate pouch and will therefore not rust or burst even under adverse weather conditions and can be guaranteed for more than two years as long as the integrity of the packaging is maintained. Safari operators in remote parts of Africa, mountaineers, yachtsmen, canoeists and geological survey teams currently use shelf-stable irradiated meat products produced in South Africa.

  4. Application of the ELDO approach to assess cumulative eye lens doses for interventional cardiologists.

    PubMed

    Farah, J; Struelens, L; Auvinen, A; Jacob, S; Koukorava, C; Schnelzer, M; Vanhavere, F; Clairand, I

    2015-04-01

    In preparation of a large European epidemiological study on the relation between eye lens dose and the occurrence of lens opacities, the European ELDO project focused on the development of practical methods to estimate retrospectively cumulative eye lens dose for interventional medical professionals exposed to radiation. The present paper applies one of the ELDO approaches, correlating eye lens dose to whole-body doses, to assess cumulative eye lens dose for 14 different Finnish interventional cardiologists for whom annual whole-body dose records were available for their entire working period. The estimated cumulative left and right eye lens dose ranged from 8 to 264 mSv and 6 to 225 mSv, respectively. In addition, calculations showed annual eye lens doses sometimes exceeding the new ICRP annual limit of 20 mSv. The work also highlights the large uncertainties associated with the application of such an approach proving the need for dedicated dosimetry systems in the routine monitoring of the eye lens dose. PMID:25316910

  5. The peripheral dose outside the applicator in electron beams of Oncor linear accelerator.

    PubMed

    Iktueren, Basak; Bilge, Hatice; Karacam, Songul; Atkovar, Gulyuz

    2012-06-01

    In this study, the peripheral dose outside the applicator was measured using electron beams produced by an Oncor linear accelerator and compared with the data of the treatment planning system (TPS). The dose profiles have been measured, by using a water-equivalent slab phantom and a parallel plate ionisation chamber, at 6, 9 and 15 MeV energy levels in 5×5, 10×10, 15×15, 20×20 and 25×25 cm(2) applicators and at 0, 10 and 20° gantry angles; and at the surface, 0.2, 0.5, 1 cm and d(max) depth for each electron energy level. The peripheral dose has been determined with these profiles by normalisation at the field central beam axis (CAX). It has been noticed that, using a 10×10 cm(2) applicator, there is a 1.4 % dose peak on the surface 6 cm away from the field edge where the field CAX is at 100 %, at a gantry angle of 0° with 6 and 9 MeV electron beams; also for the 15 MeV electron beam there is a 2.3 % dose peak. It has been discovered that the peak dose approaches a minimum depending on the increase in depth and reaches 2.5-4 % depending on the growth of the field dimension. At gantry angles of 10 and 20°, 6 and 9 MeV electron beams created small peaks and a maximum dose could be reached at 0.2 and 1 cm depth. Electron beam of 15 MeV did not peak at depths of 0.2 and 1 cm at gantry angles of 10 and 20°. The measured peripheral dose outside the applicators has been compared with the data from a TPS's computer using the Pencil Beam algorithm; it has been stated that dose calculations can be made as far as 3 cm outside the field. In conclusion, the TPS is not sufficient to measure the peripheral dose outside the applicators, and this dose can only be determined by direct measurement. PMID:22025738

  6. Influence of Metal of the Applicator on the Dose Distribution during Brachytherapy

    PubMed Central

    Wu, Chin-Hui; Shiau, An-Cheng; Liao, Yi-Jen; Lin, Hsin-Yu

    2014-01-01

    This study explores how the metal materials of the applicator influence the dose distribution when performing brachytherapy for cervical cancer. A pinpoint ionization chamber, Monte Carlo code MCNPX, and treatment planning system are used to evaluate the dose distribution for a single Ir-192 source positioned in the tandem and ovoid. For dose distribution in water with the presence of the tandem, differences among measurement, MCNPX calculation and treatment planning system results are <5%. For dose distribution in water with the presence of the ovoid, the MCNPX result agrees with the measurement. But the doses calculated from treatment planning system are overestimated by up to a factor of 4. This is due to the shielding effect of the metal materials in the applicator not being considered in the treatment planning system. This result suggests that the treatment planning system should take into account corrections for the metal materials of the applicator in order to improve the accuracy of the radiation dose delivered. PMID:25133789

  7. Dosimetric characteristics of the Leipzig surface applicators used in the high dose rate brachy radiotherapy

    SciTech Connect

    Niu Hongquan; Hsi, Wen C.; Chu, James C.H.; Kirk, Michael C.; Kouwenhoven, Erik

    2004-12-01

    The nucletron Leipzig applicator is designed for (HDR) {sup 192}Ir brachy radiotherapy of surface lesions. The dosimetric characteristics of this applicator were investigated using simulation method based on Monte Carlo N-particle (MCNP) code and phantom measurements. The simulation method was validated by comparing calculated dose rate distributions of nucletron microSelectron HDR {sup 192}Ir source against published data. Radiochromic films and metal-oxide-semiconductor field-effect transistor (MOSFET) detectors were used for phantom measurements. The double exposure technique, correcting the nonuniform film sensitivity, was applied in the film dosimetry. The linear fit of multiple readings with different irradiation times performed for each MOSFET detector measurement was used to obtain the dose rate of each measurement and to correct the source transit-time error. The film and MOSFET measurements have uncertainties of 3%-7% and 3%-5%, respectively. The dose rate distributions of the Leipzig applicator with 30 mm opening calculated by the validated MC method were verified by measurements of film and MOSFET detectors. Calculated two-dimensional planar dose rate distributions show similar patterns as the film measurement. MC calculated dose rate at a reference point defined at depth 5 mm on the applicator's central axis is 7% lower than the film and 3% higher than the MOSFET measurements. The dose rate of a Leipzig applicator with 30 mm opening at reference point is 0.241{+-}3% cGy h{sup -1} U{sup -1}. The MC calculated depth dose rates and profiles were tabulated for clinic use.

  8. Application of optical methods for dose evaluation in normoxic polyacrylamide gels irradiated at two different geometries

    NASA Astrophysics Data System (ADS)

    Adliene, D.; Jakstas, K.; Vaiciunaite, N.

    2014-03-01

    Normoxic gels are frequently used in clinical praxis for dose assessment or 3-D dose imaging in radiotherapy due to their relative simple manufacturing process under normal atmospheric conditions, spatial stability and well expressed modification feature of physical properties which is related to radiation induced polymerization of gels. In this work we have investigated radiation induced modification of the optical properties of home prepared normoxic polyacrylamide gels (nPAG) in relation to polymerization processes that occur in irradiated gels. Two irradiation geometries were used for irradiation of gel samples: broad beam irradiation geometry of teletherapy unit ROKUS-M with a 60Co source and point source irradiation geometry using 192Ir source of high dose rate afterloading brachytherapy unit MicroSelectron v2 which was inserted into gel via 6 Fr (2 mm thick) catheter. Verification of optical methods: UV-VIS spectrometry, spectrophotometry, Raman spectroscopy for dose assessment in irradiated gels has been performed. Aspects of their application for dose evaluation in gels irradiated using different geometries are discussed. Simple pixel-dose based photometry method also has been proposed and evaluated as a potential method for dose evaluation in catheter based interstitial high dose rate brachytherapy.

  9. Sub-lethal toxicity of the antiparasitic abamectin on earthworms and the application of neutral red retention time as a biomarker.

    PubMed

    Jensen, John; Diao, Xiaoping; Scott-fordsmand, Janeck J

    2007-06-01

    The antiparasitic abamectin has been proven effective against both endo- and ectoparasites of farm animals and hence used widely in animal husbandry. It may enter the soil environment with the excreta of treated animals. Very little information is available with regard to the sub-lethal effects of abamectin on soil invertebrates, such as earthworms. The objective of this study was to evaluate the toxic effect of abamectin on earthworms, using Eisenia fetida, by analyzing changes in the survival, growth, reproduction and cocoon hatchability of exposed earthworms. Furthermore, a biomarker of the lysosomal membrane stability, measured by neutral red retention time (NRR-time), was also applied. Abamectin showed significant toxicity on the growth of earthworms with increasing concentrations up to 5mg/kg. The most sensitive parameter was reproduction (cocoons production and hatchability) and NRR-time. The number of cocoons was reduced at concentrations above 0.25mg/kg and no cocoons were present at the highest concentration of 5mg/kg. Cocoons exposed to abamectin exhibited a reduced hatching success at concentrations above 1.5mg/kg. The NRR-time was reduced significantly at exposure concentrations of abamectin above 0.25mg/kg. The change in lysosomal membrane stability showed a good correlation with reproduction and may hence be a potential predicator of the effects on earthworm populations. PMID:17292446

  10. Brachytherapy Application with in situ Dose-painting Administered via Gold-nanoparticle Eluters

    PubMed Central

    Sinha, Neeharika; Cifter, Gizem; Sajo, Erno; Kumar, Rajiv; Sridhar, Srinivas; Nguyen, Paul; Cormack, Robert A; Makrigiorgos, G. Mike; Ngwa, Wilfred

    2014-01-01

    Purpose Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A proposed new strategy for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in-situ release after implantation. This in silico study investigates the intra-tumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials An experimentally determined intra-tumoral diffusion coefficient (D) for 10 nm nanoparticles was employed to estimate D for other sizes using the Stoke-Einstein equation. GNP concentration profiles, obtained using D, were then employed to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel using dose-painting by numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation is carried out as a function of GNP size for clinically applicable low dose rate brachytherapy sources: I-125, Pd-103, Cs-131. Results Results showed that dose enhancement to tumor voxels/sub-volumes during brachytherapy can be customized by varying the sizes of GNP released or eluted from the GBS. For example, using 7 mg/g GNP concentration, significant DEF (> 20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNPs sizes of 2 nm, 5 nm, 10 nm, 20 nm, 30 nm 50 nm, and 80 nm when treating with I-125. Conclusions Analyses show that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. The findings provide a useful reference for further work towards potential development of a new brachytherapy application with in-situ dose-painting administered via gold

  11. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    PubMed

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts. PMID:11695884

  12. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

    SciTech Connect

    Shwetha, Bondel; Ravikumar, Manickam; Supe, Sanjay S.; Sathiyan, Saminathan; Lokesh, Vishwanath; Keshava, Subbarao L.

    2012-04-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  13. CYTOKINE PROFILING FOR CHEMICAL SENSITIZERS: APPLICATION OF THE RIBONUCLEASE PROTECTION ASSAY AND EFFECT OF DOSE

    EPA Science Inventory

    Cytokine Profiling for Chemical Sensitizers: Application of the Ribonuclease Protection Assay and Effect of Dose. L.M. Plitnick1, S.E. Loveless3, G.S. Ladics3, M.P. Holsapple4, M.J. Selgrade2, D.M. Sailstad2 and R.J. Smialowicz2. 1UNC, Curriculum in Toxicology, Chapel Hill, NC a...

  14. APPLICATION AND USE OF DOSE ESTIMATING EXPOSURE MODEL (DEEM) FOR ROUTE TO ROUTE DOSE COMPARISONS AFTER EXPOSURE TO TRICHLOROETHYLENE (TCE)

    EPA Science Inventory

    Route-to-route extrapolations are a crucial step in many risk assessments. Often the doses which result In toxicological end points in one route must be compared with doses resulting from typical environmental exposures by another route. In this case we used EPA's Dose Estimati...

  15. APPLICATION AND USE OF DOSE ESTIMATING EXPOSURE MODEL (DEEM) FOR DOSE COMPARISONS AFTER EXPOSURE TO TRICHLOROETHYLENE (TCE)

    EPA Science Inventory

    Route-to-route extrapolations are a crucial step in many risk assessments. Often the doses which result In toxicological end points in one route must be compared with doses resulting from typical environmental exposures by another route. In this case we used EPA's Dose Estimati...

  16. Chronic exposure of corals to fine sediments: lethal and sub-lethal impacts.

    PubMed

    Flores, Florita; Hoogenboom, Mia O; Smith, Luke D; Cooper, Timothy F; Abrego, David; Negri, Andrew P

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l(-1) TSS (25 mg cm(-2) day(-1)) for M. aequituberculata and 100 mg l(-1) TSS (83 mg cm(-2) day(-1)) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  17. Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts

    PubMed Central

    Flores, Florita; Hoogenboom, Mia O.; Smith, Luke D.; Cooper, Timothy F.; Abrego, David; Negri, Andrew P.

    2012-01-01

    Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l−1 TSS (25 mg cm−2 day−1) for M. aequituberculata and 100 mg l−1 TSS (83 mg cm−2 day−1) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue. PMID:22662225

  18. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

    PubMed

    McCue, Marshall D; Guzman, R Marena; Passement, Celeste A; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation. PMID:26465334

  19. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing

    PubMed Central

    McCue, Marshall D.; Guzman, R. Marena; Passement, Celeste A.; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation. PMID:26465334

  20. Lethal infection by Bordetella pertussis mutants in the infant mouse model.

    PubMed Central

    Weiss, A A; Goodwin, M S

    1989-01-01

    Different aspects of lethal infection of infant mice with Bordetella pertussis were examined. Mutants deficient in vir-regulated genes were tested for the ability to cause a lethal infection in the infant mouse model. Adenylate cyclase toxin-hemolysin and pertussis toxin were required to cause a lethal infection at low doses. Mixed infection caused by challenging the mice with an equal number of pertussis toxin and adenylate cyclase toxin-hemolysin mutants at a dose at which neither alone was lethal was also unable to cause a lethal infection. Production of the filamentous hemagglutinin and the dermonecrotic toxin was not required to cause a lethal infection. Nine other mutants in vir-regulated genes whose phenotypes have yet to be determined were also tested. Only two of these mutants were impaired in the ability to cause a lethal infection. Expression of fimbriae does not appear to affect the dose required to cause a lethal infection; however, fimbrial expression was correlated with the later stages of a nonlethal, persistent infection. Growth of the bacteria in MgSO4, a condition which reversibly suppresses expression of the genes required for virulence, did not alter the ability of the bacteria to cause a lethal infection. Auxotrophic mutants deficient in leucine biosynthesis were as virulent as the parental strain; however, mutants deficient in methionine biosynthesis were less virulent. A B. parapertussis strain was much less effective in promoting a lethal infection than any of the wild-type B. pertussis strains examined. A persistent infection in the lungs was observed for weeks after challenge for mice given a sublethal dose of B. pertussis, and transmission from infected infants to the mother was never observed. PMID:2572561

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

    PubMed

    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. PMID:22892545

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Lethal photosensitization of biofilm-grown bacteria

    NASA Astrophysics Data System (ADS)

    Wilson, Michael

    1997-12-01

    Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

  4. Subcutaneous wounding postirradiation reduces radiation lethality in mice.

    PubMed

    Garrett, Joy; Orschell, Christie M; Mendonca, Marc S; Bigsby, Robert M; Dynlacht, Joseph R

    2014-06-01

    The detonation of an improvised nuclear device during a radiological terrorist attack could result in the exposure of thousands of civilians and first responders to lethal or potentially lethal doses of ionizing radiation (IR). There is a major effort in the United States to develop phamacological mitigators of radiation lethality that would be effective particularly if administered after irradiation. We show here that giving female C57BL/6 mice a subcutaneous surgical incision after whole body exposure to an LD50/30 X-ray dose protects against radiation lethality and increases survival from 50% to over 90% (P = 0.0001). The increase in survival, at least in part, appears to be due to enhanced recovery of hematopoiesis, notably red blood cells, neutrophils and platelets. While a definitive mechanism has yet to be elucidated, we propose that this approach may be used to identify potentially novel mechanisms and pathways that could aid in the development of novel pharmacological radiation countermeasures. PMID:24811864

  5. Comparison of doses to the rectum derived from treatment planning system with in-vivo dose values in vaginal vault brachytherapy using cylinder applicators

    PubMed Central

    Obed, Rachel Ibhade; Akinlade, Bidemi Idayat; Ntekim, Atara

    2015-01-01

    Purpose In-vivo measurements to determine doses to organs-at-risk can be an essential part of brachytherapy quality assurance (QA). This study compares calculated doses to the rectum with measured dose values as a means of QA in vaginal vault brachytherapy using cylinder applicators. Material and methods At the Department of Radiotherapy, University College Hospital (UCH), Ibadan, Nigeria, intracavitary brachytherapy (ICBT) was delivered by a GyneSource high-dose-rate (HDR) unit with 60Co. Standard 2D treatment plans were created with HDR basic 2.6 software for prescription doses 5-7 Gy at points 5 mm away from the posterior surface of vaginal cylinder applicators (20, 25, and 30 mm diameters). The LiF:Mg, Ti thermoluminescent dosimeter rods (1 x 6 mm) were irradiated to a dose of 7 Gy on Theratron 60Co machine for calibration purpose prior to clinical use. Measurements in each of 34 insertions involving fourteen patients were performed with 5 TLD-100 rods placed along a re-usable rectal marker positioned in the rectum. The dosimeters were read in Harshaw 3500 TLD reader and compared with doses derived from the treatment planning system (TPS) at 1 cm away from the dose prescription points. Results The mean calculated and measured doses ranged from 2.1-3.8 Gy and 1.2-5.6 Gy with averages of 3.0 ± 0.5 Gy and 3.1 ± 1.1 Gy, respectively, for treatment lengths 2-8 cm along the cylinder-applicators. The mean values correspond to 48.9% and 50.8% of the prescribed doses, respectively. The deviations of the mean in-vivo doses from the TPS values ranged from –1.9 to 2.1 Gy with a p-value of 0.427. Conclusions This study was part of efforts to verify rectal dose obtained from the TPS during vaginal vault brachytherapy. There was no significant difference in the dose to the rectum from the two methods of measurements. PMID:26816506

  6. Benchmarking of Monte Carlo based shutdown dose rate calculations for applications to JET.

    PubMed

    Petrizzi, L; Batistoni, P; Fischer, U; Loughlin, M; Pereslavtsev, P; Villari, R

    2005-01-01

    The calculation of dose rates after shutdown is an important issue for operating nuclear reactors. A validated computational tool is needed for reliable dose rate calculations. In fusion reactors neutrons induce high levels of radioactivity and presumably high doses. The complex geometries of the devices require the use of sophisticated geometry modelling and computational tools for transport calculations. Simple rule of thumb laws do not always apply well. Two computational procedures have been developed recently and applied to fusion machines. Comparisons between the two methods showed some inherent discrepancies when applied to calculation for the ITER while good agreement was found for a 14 MeV point source neutron benchmark experiment. Further benchmarks were considered necessary to investigate in more detail the reasons for the different results in different cases. In this frame the application to the Joint European Torus JET machine has been considered as a useful benchmark exercise. In a first calculational benchmark with a representative D-T irradiation history of JET the two methods differed by no more than 25%. In another, more realistic benchmark exercise, which is the subject of this paper, the real irradiation history of D-T and D-D campaigns conducted at JET in 1997-98 were used to calculate the shut-down doses at different locations, irradiation and decay times. Experimental dose data recorded at JET for the same conditions offer the possibility to check the prediction capability of the calculations and thus show the applicability (and the constraints) of the procedures and data to the rather complex shutdown dose rate analysis of real fusion devices. Calculation results obtained by the two methods are reported below, comparison with experimental results give discrepancies ranging between 2 and 10. The reasons of that can be ascribed to the high uncertainty on the experimental data and the unsatisfactory JET model used in the calculation. A new

  7. Antagonistic antibody prevents toll-like receptor 2–driven lethal shock-like syndromes

    PubMed Central

    Meng, Guangxun; Rutz, Mark; Schiemann, Matthias; Metzger, Jochen; Grabiec, Alina; Schwandner, Ralf; Luppa, Peter B.; Ebel, Frank; Busch, Dirk H.; Bauer, Stefan; Wagner, Hermann; Kirschning, Carsten J.

    2004-01-01

    Hyperactivation of immune cells by bacterial products through toll-like receptors (TLRs) is thought of as a causative mechanism of septic shock pathology. Infections with Gram-negative or Gram-positive bacteria provide TLR2-specific agonists and are the major cause of severe sepsis. In order to intervene in TLR2-driven toxemia, we raised mAb’s against the extracellular domain of TLR2. Surface plasmon resonance analysis showed direct and specific interaction of TLR2 and immunostimulatory lipopeptide, which was blocked by T2.5 in a dose-dependent manner. Application of mAb T2.5 inhibited cell activation in experimental murine models of infection. T2.5 also antagonized TLR2-specific activation of primary human macrophages. TLR2 surface expression by murine macrophages was surprisingly weak, while both intra- and extracellular expression increased upon systemic microbial challenge. Systemic application of T2.5 upon lipopeptide challenge inhibited release of inflammatory mediators such as TNF-α and prevented lethal shock-like syndrome in mice. Twenty milligrams per kilogram of T2.5 was sufficient to protect mice, and administration of 40 mg/kg of T2.5 was protective even 3 hours after the start of otherwise lethal challenge with Bacillus subtilis. These results indicate that epitope-specific binding of exogenous ligands precedes specific TLR signaling and suggest therapeutic application of a neutralizing anti-TLR2 antibody in acute infection. PMID:15146245

  8. Numerical model for computation of effective and ambient dose equivalent at flight altitudes. Application for dose assessment during GLEs

    NASA Astrophysics Data System (ADS)

    Mishev, Alexander; Usoskin, Ilya

    2015-05-01

    A numerical model for assessment of the effective dose and ambient dose equivalent produced by secondary cosmic ray particles of galactic and solar origin at commercial aircraft altitudes is presented. The model represents a full chain analysis based on ground-based measurements of cosmic rays, from particle spectral and angular characteristics to dose estimation. The model is based on newly numerically computed yield functions and realistic propagation of cosmic ray in the Earth magnetosphere. The yield functions are computed using a straightforward full Monte Carlo simulation of the atmospheric cascade induced by primary protons and α-particles and subsequent conversion of secondary particle fluence (neutrons, protons, gammas, electrons, positrons, muons and charged pions) to effective dose or the ambient dose equivalent. The ambient dose equivalent is compared with reference data at various conditions such as rigidity cut-off and level of solar activity. The method is applied for computation of the effective dose rate at flight altitude during the ground level enhancement of 13 December 2006. The solar proton spectra are derived using neutron monitor data. The computation of the effective dose rate during the event explicitly considers the derived anisotropy i.e. the pitch angle distribution as well as the propagation of the solar protons in the magnetosphere of the Earth.

  9. Application of laser TLD 2-dimensional dose mapping in medical physics

    SciTech Connect

    Braunlich, P.F.; Jones, S.C.

    1995-12-31

    IST, Inc. has developed a laser-based system for rapid evaluation of two-dimensional monolithic thermoluminescence dosimetry (TLD) films. For most applications, the authors use arrays of 1.5- mm diameter, 38-{mu}m-thick TLDs, deposited on 0.125-mm-thick polymer in a 3x3-mm grid of up to 30x30-cm size. Continuous films are available for applications requiring higher spatial resolution (300 {mu}m.) The films are re-usable and water-immersible. Results from radiation therapy (photon and charged particle beam) dose measurements, quality assurance in mammography (dose distribution and kVp), interventional radiotherapy and personnel dosimetry (detection of intentional fraudulent exposures) are given.

  10. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    SciTech Connect

    Sinha, Neeharika; Cifter, Gizem; Sajo, Erno; Kumar, Rajiv; Sridhar, Srinivas; Nguyen, Paul L.; Cormack, Robert A.; Makrigiorgos, G. Mike; Ngwa, Wilfred

    2015-02-01

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application with

  11. Application of the new MultiTrans SP3 radiation transport code in BNCT dose planning.

    PubMed

    Kotiluoto, P; Hiisamäki, P; Savolainen, S

    2001-09-01

    Dose planning in boron neutron capture therapy (BNCT) is a complex problem and requires sophisticated numerical methods. In the framework of the Finnish BNCT project, new deterministic three-dimensional radiation transport code MultiTrans SP3 has been developed at VTT Chemical Technology, based on a novel application of the tree multigrid technique. To test the applicability of this new code in a realistic BNCT dose planning problem, cylindrical PMMA (polymethyl-methacrylate) phantom was chosen as a benchmark case. It is a convenient benchmark, as it has been modeled by several different codes, including well-known DORT and MCNP. Extensive measured data also exist. In this paper, a comparison of the new MultiTrans SP3 code with other methods is presented for the PMMA phantom case. Results show that the total neutron dose rate to ICRU adult brain calculated by the MultiTrans SP3 code differs less than 4% in 2 cm depth in phantom (in thermal maximum) from the DORT calculation. Results also show that the calculated 197Au(n,gamma) and 55Mn(n,gamma) reaction rates in 2 cm depth in phantom differ less than 4% and 1% from the measured values, respectively. However, the photon dose calculated by the MultiTrans SP3 code seems to be incorrect in this PMMA phantom case, which requires further studying. As expected, the deterministic MultiTrans SP3 code is over an order of magnitude faster than stochastic Monte Carlo codes (with similar resolution), thus providing a very efficient tool for BNCT dose planning. PMID:11585221

  12. Syn-Lethality: An Integrative Knowledge Base of Synthetic Lethality towards Discovery of Selective Anticancer Therapies

    PubMed Central

    Li, Xue-juan; Mishra, Shital K.; Wu, Min; Zhang, Fan

    2014-01-01

    Synthetic lethality (SL) is a novel strategy for anticancer therapies, whereby mutations of two genes will kill a cell but mutation of a single gene will not. Therefore, a cancer-specific mutation combined with a drug-induced mutation, if they have SL interactions, will selectively kill cancer cells. While numerous SL interactions have been identified in yeast, only a few have been known in human. There is a pressing need to systematically discover and understand SL interactions specific to human cancer. In this paper, we present Syn-Lethality, the first integrative knowledge base of SL that is dedicated to human cancer. It integrates experimentally discovered and verified human SL gene pairs into a network, associated with annotations of gene function, pathway, and molecular mechanisms. It also includes yeast SL genes from high-throughput screenings which are mapped to orthologous human genes. Such an integrative knowledge base, organized as a relational database with user interface for searching and network visualization, will greatly expedite the discovery of novel anticancer drug targets based on synthetic lethality interactions. The database can be downloaded as a stand-alone Java application. PMID:24864230

  13. Dosimetric impact of applicator displacement during high dose rate (HDR) Cobalt-60 brachytherapy for cervical cancer: A planning study

    NASA Astrophysics Data System (ADS)

    Yong, J. S.; Ung, N. M.; Jamalludin, Z.; Malik, R. A.; Wong, J. H. D.; Liew, Y. M.; Ng, K. H.

    2016-02-01

    We investigated the dosimetric impact of applicator displacement on dose specification during high dose rate (HDR) Cobalt-60 (Co-60) brachytherapy for cervical cancer through a planning study. Eighteen randomly selected HDR full insertion plans were restrospectively studied. The tandem and ovoids were virtually shifted translationally and rotationally in the x-, y- and z-axis directions on the treatment planning system. Doses to reference points and volumes of interest in the plans with shifted applicators were compared with the original plans. The impact of dose displacement on 2D (point-based) and 3D (volume-based) treatment planning techniques was also assessed. A ±2 mm translational y-axis applicator shift and ±4° rotational x-axis applicator shift resulted in dosimetric changes of more than 5% to organs at risk (OAR) reference points. Changes to the maximum doses to 2 cc of the organ (D2cc) in 3D planning were statistically significant and higher than the reference points in 2D planning for both the rectum and bladder (p<0.05). Rectal D2cc was observed to be the most sensitive to applicator displacement among all dose metrics. Applicator displacement that is greater than ±2 mm translational y-axis and ±4° rotational x-axis resulted in significant dose changes to the OAR. Thus, steps must be taken to minimize the possibility of applicator displacement during brachytherapy.

  14. Dosimetric characterization of surface applicators for use with high dose rate Iridium-192 and electronic brachytherapy sources

    NASA Astrophysics Data System (ADS)

    Fulkerson, Regina Kennedy

    Historically, treatment of malignant surface lesions has been achieved with linear accelerator based electron beams or superficial x-ray beams. Recent developments in the field of brachytherapy now allow for the treatment of surface lesions with specialized conical applicators placed directly on the lesion. Applicators are available for use with high dose rate 192Ir sources, as well as electronic brachytherapy sources. Although use of these applicators has gained in popularity, the dosimetric characteristics including depth dose and surface dose distributions have not been independently verified. Additionally, there is no recognized method of output verification for quality assurance procedures with applicators like these. Existing dosimetry protocols available from the American Association of Physicists in Medicine (AAPM) bookend the cross-over characteristics of a traditional brachytherapy source (as described by Task Group 43) being implemented as a low-energy superficial x-ray beam (as described by Task Group 61) as observed with the surface applicators of interest. This thesis work aims to create a cohesive method of output verification that can be used to determine the dose at the treatment surface as part of a quality assurance/commissioning process for surface applicators used with high dose rate 192Ir and electronic brachytherapy sources. Air-kerma rate measurements were completed with an Attix Free-Air Chamber, as well as several models of small-volume ionization chambers to obtain an air-kerma rate at the treatment surface for each applicator. Correction factors were calculated using MCNP5 and EGSnrc Monte Carlo codes in order to determine an applicator-specific absorbed dose to water at the treatment surface from the measured air-kerma rate. Additionally, relative dose measurements of the surface dose distributions and characteristic depth dose curves were completed in-phantom and in-water. Theoretical dose distributions and depth dose curves were

  15. Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators

    SciTech Connect

    Eichmann, Marion; Fluehs, Dirk; Spaan, Bernhard

    2009-10-15

    Purpose: The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. Methods: In order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. Results: The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. Conclusions: The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate

  16. Evaluation of low energy electron beam dose application by means of a portable optical device

    NASA Astrophysics Data System (ADS)

    Reitzig, Manuela; Winkler, Martin; Härtling, Thomas; Röder, Olaf; Opitz, Jörg

    2014-11-01

    We present our recent development concerning the evaluation of a low energy dose application to electron beam responding materials with a simple portable optical device. Electron beam irradiation is a promising option to sterilize sensitive and high performance products or surfaces at a low temperature and without moisture. Especially in the fields of the food industry and medicine, regulations regarding sterility are increasingly tightened. Because of this, a secure proof for electron-beam-assisted sterilization is required. However, no nondestructive and in situ method exists up until now. Our approach to provide a secure proof of sterilization is to place a suitable marker material based on rare-earth-doped phosphors inside or on the top of the packaging material of the respective product. Upon electron irradiation the marker material changes its luminescence properties as a function of the applied energy dose. We verified the energy dependence by means of time-resolved measurements of the luminescence decay of an upconversion phosphor with a portable optical device. In our experimental realization, short laser pulses in the near-infrared range are triggered by a microcontrol unit (MCU) and excite the marker material. The light emitted by the marker is collected in the range between 400 and 1100 nm via a silicon photodiode, processed by the MCU, and analyzed in a Labview program via a single-exponential fit. As a main result, we observe an increasing reduction of the luminescence lifetime with higher dose applications.

  17. Dose properties of a laser accelerated electron beam and prospects for clinical application.

    PubMed

    Kainz, K K; Hogstrom, K R; Antolak, J A; Almond, P R; Bloch, C D; Chiu, C; Fomytskyi, M; Raischel, F; Downer, M; Tajima, T

    2004-07-01

    Laser wakefield acceleration (LWFA) technology has evolved to where it should be evaluated for its potential as a future competitor to existing technology that produces electron and x-ray beams. The purpose of the present work is to investigate the dosimetric properties of an electron beam that should be achievable using existing LWFA technology, and to document the necessary improvements to make radiotherapy application for LWFA viable. This paper first qualitatively reviews the fundamental principles of LWFA and describes a potential design for a 30 cm accelerator chamber containing a gas target. Electron beam energy spectra, upon which our dose calculations are based, were obtained from a uniform energy distribution and from two-dimensional particle-in-cell (2D PIC) simulations. The 2D PIC simulation parameters are consistent with those reported by a previous LWFA experiment. According to the 2D PIC simulations, only approximately 0.3% of the LWFA electrons are emitted with an energy greater than 1 MeV. We studied only the high-energy electrons to determine their potential for clinical electron beams of central energy from 9 to 21 MeV. Each electron beam was broadened and flattened by designing a dual scattering foil system to produce a uniform beam (103%>off-axis ratio>95%) over a 25 x 25 cm2 field. An energy window (deltaE) ranging from 0.5 to 6.5 MeV was selected to study central-axis depth dose, beam flatness, and dose rate. Dose was calculated in water at a 100 cm source-to-surface distance using the EGS/BEAM Monte Carlo algorithm. Calculations showed that the beam flatness was fairly insensitive to deltaE. However, since the falloff of the depth-dose curve (R10-R90) and the dose rate both increase with deltaE, a tradeoff between minimizing (R10-R90) and maximizing dose rate is implied. If deltaE is constrained so that R10-R90 is within 0.5 cm of its value for a monoenergetic beam, the maximum practical dose rate based on 2D PIC is approximately 0.1 Gy min

  18. Comparison between beta radiation dose distribution due to LDR and HDR ocular brachytherapy applicators using GATE Monte Carlo platform.

    PubMed

    Mostafa, Laoues; Rachid, Khelifi; Ahmed, Sidi Moussa

    2016-08-01

    Eye applicators with 90Sr/90Y and 106Ru/106Rh beta-ray sources are generally used in brachytherapy for the treatment of eye diseases as uveal melanoma. Whenever, radiation is used in treatment, dosimetry is essential. However, knowledge of the exact dose distribution is a critical decision-making to the outcome of the treatment. The Monte Carlo technique provides a powerful tool for calculation of the dose and dose distributions which helps to predict and determine the doses from different shapes of various types of eye applicators more accurately. The aim of this work consisted in using the Monte Carlo GATE platform to calculate the 3D dose distribution on a mathematical model of the human eye according to international recommendations. Mathematical models were developed for four ophthalmic applicators, two HDR 90Sr applicators SIA.20 and SIA.6, and two LDR 106Ru applicators, a concave CCB model and a flat CCB model. In present work, considering a heterogeneous eye phantom and the chosen tumor, obtained results with the use of GATE for mean doses distributions in a phantom and according to international recommendations show a discrepancy with respect to those specified by the manufacturers. The QC of dosimetric parameters shows that contrarily to the other applicators, the SIA.20 applicator is consistent with recommendations. The GATE platform show that the SIA.20 applicator present better results, namely the dose delivered to critical structures were lower compared to those obtained for the other applicators, and the SIA.6 applicator, simulated with MCNPX generates higher lens doses than those generated by GATE. PMID:27499370

  19. Tasers--less than lethal!

    PubMed

    Sharma, Abiram; Theivacumar, Nada S; Souka, Hesham M

    2009-05-01

    We report a case of potentially lethal injury associated with the use of Taser. A 42-year-old man was stopped by police for potential detention. He held a large carving knife over his epigasrium threatening to stab himself. With a view to achieving immobilisation, a Taser gun was used. On activation of the Taser, the subject suffered a 7-cm wide and 10-cm deep stab injury to the upper abdomen. In this case, activation of the Taser resulted in the contraction of skeletal muscles, flexors more intensely than extensors, resulting in the stab injury. PMID:19416583

  20. Tasers – Less than Lethal!

    PubMed Central

    Sharma, Abiram; Theivacumar, Nada S; Souka, Hesham M

    2009-01-01

    We report a case of potentially lethal injury associated with the use of Taser. A 42-year-old man was stopped by police for potential detention. He held a large carving knife over his epigasrium threatening to stab himself.With a view to achieving immobilisation, a Taser gun was used. On activation of the Taser, the subject suffered a 7-cm wide and 10-cm deep stab injury to the upper abdomen. In this case, activation of the Taser resulted in the contraction of skeletal muscles, flexors more intensely than extensors, resulting in the stab injury. PMID:19416583

  1. Considerations in the application of the electronic dosimeter to dose of record

    SciTech Connect

    Swinth, K.L.

    1997-12-01

    This report describes considerations for application of the electronic dosimeter (ED) as a measurement device for the dose of record (primary dosimetry). EDs are widely used for secondary dosimetry and advances in their reliability and capabilities have resulted in interest in their use to meet the needs of both primary and secondary dosimetry. However, the ED is an active device and more complex than the thermoluminescent and film dosimeters now in use for primary dosimetry. The user must evaluate the ED in terms of reliability, serviceability and radiations detected its intended application(s). If an ED is selected for primary dosimetry, the user must establish methods both for controlling the performance of the ED to ensure long term reliability of the measurements and for their proper use as a primary dosimeter. Regulatory groups may also want to develop methods to ensure adequate performance of the ED for dose of record. The purpose of the report is to provide an overview of considerations in the use of the ED for primary dosimetry. Considerations include recognizing current limitations, type testing of EDs, testing by the user, approval performance testing, calibration, and procedures to integrate the dosimeter into the users program.

  2. IMPROVEMENT OF EXPOSURE-DOSE MODELS: APPLICATION OF CONTINUOUS BREATH SAMPLING TO DETERMINE VOC DOSE AND BODY BURDEN

    EPA Science Inventory

    This is a continuation of an Internal Grant research project with the focus on completing the research due to initial funding delays and then analyzing and reporting the research results. This project will employ a new continuous breath sampling methodology to investigate dose a...

  3. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    PubMed

    Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

    2010-07-01

    Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia. PMID:20558844

  4. Electroshock weapons can be lethal!

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2008-03-01

    Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

  5. Lethal domestic violence in eastern North Carolina.

    PubMed

    Gilliland, M G; Spence, P R; Spence, R L

    2000-01-01

    Strategies for preventing domestic violence can be tailored to a particular geographic or socioeconomic area if the patterns of domestic violence in the area are known. National statistics, although widely available, may not be applicable to a specific region. We reviewed homicide deaths in Eastern North Carolina between 1978 and 1999 to identify patterns in this rural area. Approximately 20% of the homicide deaths in eastern North Carolina are caused by intimate partners. Women accounted for 53% of the victims in 1976, similar to national figures but not rising to 72% as seen nationally in 1998. Latinos are an increasing presence in the area, but had only one recorded episode of lethal violence against an intimate partner. Gunshots accounted for most of the deaths (59% in men, 72% in women). Knowledge of such patterns can assist in selecting prevention strategies for this particular area. Over the last 25 years increasing attention has been devoted to domestic violence (DV), initially defined as abuse committed against a spouse, former spouse, fiancée, boy- or girlfriend, or cohabitant. As time has passed, the definition has been broadened to include other family members--elders, children, and siblings. The Centers for Disease Control and Prevention (CDC) now uses the term "intimate partner violence" for intentional emotional or physical abuse inflicted by a spouse, ex-spouse, a present or former boy- or girlfriend, or date. For the purposes of this paper, we consider DV interchangeable with intimate partner violence. There has been a national concern that abusive events are under-reported. The National Crime Victimization Survey, an anonymous household survey, indicated nearly 1 million incidents of non-lethal intimate partner violence per year between 1992 and 1996. The number decreased from 1.1 million in 1993 to 840,000 in 1996. Attempts to validate such data for a given geographic area often require subjects to violate anonymity--this may account for lower

  6. Uncertainties in Assesment of the Vaginal Dose for Intracavitary Brachytherapy of Cervical Cancer using a Tandem-ring Applicator

    SciTech Connect

    Berger, Daniel . E-mail: daniel.berger@akhwien.at; Dimopoulos, Johannes; Georg, Petra; Georg, Dietmar; Poetter, Richard; Kirisits, Christian

    2007-04-01

    Purpose: The vagina has not been widely recognized as organ at risk in brachytherapy for cervical cancer. No widely accepted dose parameters are available. This study analyzes the uncertainties in dose reporting for the vaginal wall using tandem-ring applicators. Methods and Materials: Organ wall contours were delineated on axial magnetic resonance (MR) slices to perform dose-volume histogram (DVH) analysis. Different DVH parameters were used in a feasibility study based on 40 magnetic resonance imaging (MRI)-based treatment plans of different cervical cancer patients. Dose to the most irradiated, 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, and at defined points on the ring surface and at 5-mm tissue depth were reported. Treatment-planning systems allow different methods of dose point definition. Film dosimetry was used to verify the maximum dose at the surface of the ring applicator in an experimental setup. Results: Dose reporting for the vagina is extremely sensitive to geometrical uncertainties with variations of 25% for 1 mm shifts. Accurate delineation of the vaginal wall is limited by the finite pixel size of MRI and available treatment-planning systems. No significant correlation was found between dose-point and dose-volume parameters. The DVH parameters were often related to noncontiguous volumes and were not able to detect very different situations of spatial dose distributions inside the vaginal wall. Deviations between measured and calculated doses were up to 21%. Conclusions: Reporting either point dose values or DVH parameters for the vaginal wall is based on high inaccuracies because of contouring and geometric positioning. Therefore, the use of prospective dose constraints for individual treatment plans is not to be recommended at present. However, for large patient groups treated within one protocol correlation with vaginal morbidity can be evaluated.

  7. Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

    PubMed

    Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

    2016-04-01

    Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. PMID:26493272

  8. Effect of syngeneic marrow injection upon recovery in sub- and near-lethally irradiated mice

    SciTech Connect

    Boggs, S.S.; Boggs, D.R.; Patrene, K.D.

    1989-06-01

    Mice were given sub-lethal (200-600 cGy) or near-lethal (800 cGy) whole body irradiation and the effect of injecting syngeneic marrow on subsequent hematopoietic recovery was studied. Marrow cell injection enhanced erythropoietic recovery after sub-lethal irradiation as reflected in hematocrit values and rate of appearance of /sup 59/Fe-labeled red cells in blood. However, this enhanced erythropoiesis was only seen in the spleen, and /sup 59/Fe uptake in marrow was reduced. When the irradiation dose was kept constant and the marrow dose increased from 10(5) to 10(6) to 10(7) cells, there was a somewhat erratic increase in spleen /sup 59/Fe and a decrease in marrow /sup 59/Fe uptake. When marrow cell number was kept constant and the dose of irradiation was increased from 200 to 400 to 600 to 800 cGy, there was an exponential increase in spleen /sup 59/Fe uptake but the marrow /sup 59/Fe uptake changed from depressed after lower doses to increased after 800 cGy. Cell injection after sub-lethal irradiation did not increase or decrease granulocytopoiesis. Injection of irradiated marrow cells also reduced marrow erythropoiesis and this was evident after both sub- and near-lethal irradiation. However, injection of irradiated cells did not increase splenic erythropoiesis. Following splenectomy, the depressed marrow erythropoiesis attending injection of viable cells was virtually eliminated but no increase was seen. These data suggest that the injection of autologous or syngeneic marrow may not be effective as a means of accelerating hematopoietic recovery after irradiation unless near-lethal or lethal dose have been received.

  9. Personnel neutron dose assessment upgrade: Volume 2, Field neutron spectrometer for health physics applications

    SciTech Connect

    Brackenbush, L.W.; Reece, W.D.; Miller, S.D.; Endres, G.W.R.; Durham, J.S.; Scherpelz, R.I.; Tomeraasen, P.L.; Stroud, C.M.; Faust, L.G.; Vallario, E.J.

    1988-07-01

    Both the (ICRP) and the (NCPR) have recommended an increase in neutron quality factors and the adoption of effective dose equivalent methods. The series of reports entitled Personnel Neutron Dose Assessment Upgrade (PNL-6620) addresses these changes. Volume 1 in this series of reports (Personnel Neutron Dosimetry Assessment) provided guidance on the characteristics, use, and calibration of personnel neutron dosimeters in order to meet the new recommendations. This report, Volume 2: Field Neutron Spectrometer for Health Physics Applications describes the development of a portable field spectrometer which can be set up for use in a few minutes by a single person. The field spectrometer described herein represents a significant advance in improving the accuracy of neutron dose assessment. It permits an immediate analysis of the energy spectral distribution associated with the radiation from which neutron quality factor can be determined. It is now possible to depart from the use of maximum Q by determining and realistically applying a lower Q based on spectral data. The field spectrometer is made up of two modules: a detector module with built-in electronics and an analysis module with a IBM PC/reg sign/-compatible computer to control the data acquisition and analysis of data in the field. The unit is simple enough to allow the operator to perform spectral measurements with minimal training. The instrument is intended for use in steady-state radiation fields with neutrons energies covering the fission spectrum range. The prototype field spectrometer has been field tested in plutonium processing facilities, and has been proven to operate satisfactorily. The prototype field spectrometer uses a /sup 3/He proportional counter to measure the neutron energy spectrum between 50 keV and 5 MeV and a tissue equivalent proportional counter (TEPC) to measure absorbed neutron dose.

  10. Measurement of radiation dose with BeO dosimeters using optically stimulated luminescence technique in radiotherapy applications.

    PubMed

    Şahin, Serdar; Güneş Tanır, A; Meriç, Niyazi; Aydınkarahaliloğlu, Ercan

    2015-09-01

    The radiation dose delivered to the target by using different radiotherapy applications has been measured with the help of beryllium oxide (BeO) dosimeters to be placed inside the rando phantom. Three-Dimensional Conformal Radiotherapy (3DCRT), Intensity-Modulated Radiotherapy (IMRT) and Intensity-Modulated Arc Therapy (IMAT) have been used as radiotherapy application. Individual treatment plans have been made for the three radiotherapy applications of rando phantom. The section 4 on the phantom was selected as target and 200 cGy doses were delivered. After the dosimeters placed on section 4 (target) and the sections 2 and 6 (non-target) were irradiated, the result was read through the OSL technique on the Risø TL/OSL system. This procedure was repeated three times for each radiotherapy application. The doses delivered to the target and the non-target sections as a result of the 3DCRT, IMRT and IMAT plans were analyzed. The doses received by the target were measured as 204.71 cGy, 204.76 cGy and 205.65 cGy, respectively. The dose values obtained from treatment planning system (TPS) were compared to the dose values obtained using the OSL technique. It has been concluded that, the radiation dose can be measured with the OSL technique by using BeO dosimeters in medical practices. PMID:26046521

  11. Dosimetric characterization and output verification for conical brachytherapy surface applicators. Part II. High dose rate {sup 192}Ir sources

    SciTech Connect

    Fulkerson, Regina K. Micka, John A.; DeWerd, Larry A.

    2014-02-15

    Purpose: Historically, treatment of malignant surface lesions has been achieved with linear accelerator based electron beams or superficial x-ray beams. Recent developments in the field of brachytherapy now allow for the treatment of surface lesions with specialized conical applicators placed directly on the lesion. Applicators are available for use with high dose rate (HDR){sup 192}Ir sources, as well as electronic brachytherapy sources. Part I of this paper discussed the applicators used with electronic brachytherapy sources. Part II will discuss those used with HDR {sup 192}Ir sources. Although the use of these applicators has gained in popularity, the dosimetric characteristics have not been independently verified. Additionally, there is no recognized method of output verification for quality assurance procedures with applicators like these. Methods: This work aims to create a cohesive method of output verification that can be used to determine the dose at the treatment surface as part of a quality assurance/commissioning process for surface applicators used with HDR electronic brachytherapy sources (Part I) and{sup 192}Ir sources (Part II). Air-kerma rate measurements for the {sup 192}Ir sources were completed with several models of small-volume ionization chambers to obtain an air-kerma rate at the treatment surface for each applicator. Correction factors were calculated using MCNP5 and EGSnrc Monte Carlo codes in order to determine an applicator-specific absorbed dose to water at the treatment surface from the measured air-kerma rate. Additionally, relative dose measurements of the surface dose distributions and characteristic depth dose curves were completed in-phantom. Results: Theoretical dose distributions and depth dose curves were generated for each applicator and agreed well with the measured values. A method of output verification was created that allows users to determine the applicator-specific dose to water at the treatment surface based on a

  12. Mechanical Performance of Ferritic Martensitic Steels for High Dose Applications in Advanced Nuclear Reactors

    NASA Astrophysics Data System (ADS)

    Anderoglu, Osman; Byun, Thak Sang; Toloczko, Mychailo; Maloy, Stuart A.

    2013-01-01

    Ferritic/martensitic (F/M) steels are considered for core applications and pressure vessels in Generation IV reactors as well as first walls and blankets for fusion reactors. There are significant scientific data on testing and industrial experience in making this class of alloys worldwide. This experience makes F/M steels an attractive candidate. In this article, tensile behavior, fracture toughness and impact property, and creep behavior of the F/M steels under neutron irradiations to high doses with a focus on high Cr content (8 to 12) are reviewed. Tensile properties are very sensitive to irradiation temperature. Increase in yield and tensile strength (hardening) is accompanied with a loss of ductility and starts at very low doses under irradiation. The degradation of mechanical properties is most pronounced at <0.3 T M ( T M is melting temperature) and up to 10 dpa (displacement per atom). Ferritic/martensitic steels exhibit a high fracture toughness after irradiation at all temperatures even below 673 K (400 °C), except when tested at room temperature after irradiations below 673 K (400 °C), which shows a significant reduction in fracture toughness. Creep studies showed that for the range of expected stresses in a reactor environment, the stress exponent is expected to be approximately one and the steady state creep rate in the absence of swelling is usually better than austenitic stainless steels both in terms of the creep rate and the temperature sensitivity of creep. In short, F/M steels show excellent promise for high dose applications in nuclear reactors.

  13. Computed radiography as a gamma ray detector--dose response and applications.

    PubMed

    O'Keeffe, D S; McLeod, R W

    2004-08-21

    Computed radiography (CR) can be used for imaging the spatial distribution of photon emissions from radionuclides. Its wide dynamic range and good response to medium energy gamma rays reduces the need for long exposure times. Measurements of small doses can be performed without having to pre-sensitize the computed radiography plates via an x-ray exposure, as required with screen-film systems. Cassette-based Agfa MD30 and Kodak GP25 CR plates were used in applications involving the detection of gamma ray emissions from technetium-99m and iodine-131. Cassette entrance doses as small as 1 microGy (140 keV gamma rays) produce noisy images, but the images are suitable for applications such as the detection of breaks in radiation protection barriers. A consequence of the gamma ray sensitivity of CR plates is the possibility that some nuclear medicine patients may fog their x-rays if the x-ray is taken soon after their radiopharmaceutical injection. The investigation showed that such fogging is likely to be diffuse. PMID:15446787

  14. Application of dose kernel calculation using a simplified Monte Carlo method to treatment plan for scanned proton beams.

    PubMed

    Mizutani, Shohei; Takada, Yoshihisa; Kohno, Ryosuke; Hotta, Kenji; Tansho, Ryohei; Akimoto, Tetsuo

    2016-01-01

    Full Monte Carlo (FMC) calculation of dose distribution has been recognized to have superior accuracy, compared with the pencil beam algorithm (PBA). However, since the FMC methods require long calculation time, it is difficult to apply them to routine treatment planning at present. In order to improve the situation, a simplified Monte Carlo (SMC) method has been introduced to the dose kernel calculation applicable to dose optimization procedure for the proton pencil beam scanning. We have evaluated accuracy of the SMC calculation by comparing a result of the dose kernel calculation using the SMC method with that using the FMC method in an inhomogeneous phantom. The dose distribution obtained by the SMC method was in good agreement with that obtained by the FMC method. To assess the usefulness of SMC calculation in clinical situations, we have compared results of the dose calculation using the SMC with those using the PBA method for three clinical cases of tumor treatment. The dose distributions calculated with the PBA dose kernels appear to be homogeneous in the planning target volumes (PTVs). In practice, the dose distributions calculated with the SMC dose kernels with the spot weights optimized with the PBA method show largely inhomogeneous dose distributions in the PTVs, while those with the spot weights optimized with the SMC method have moderately homogeneous distributions in the PTVs. Calculation using the SMC method is faster than that using the GEANT4 by three orders of magnitude. In addition, the graphic processing unit (GPU) boosts the calculation speed by 13times for the treatment planning using the SMC method. Thence, the SMC method will be applicable to routine clinical treatment planning for reproduc-tion of the complex dose distribution more accurately than the PBA method in a reasonably short time by use of the GPU-based calculation engine. PMID:27074456

  15. Dosimetric characterization of a novel intracavitary mold applicator for 192Ir high dose rate endorectal brachytherapy treatment.

    PubMed

    Poon, Emily; Reniers, Brigitte; Devic, Slobodan; Vuong, Té; Verhaegen, Frank

    2006-12-01

    The dosimetric properties of a novel intracavitary mold applicator for 192Ir high dose rate (HDR) endorectal cancer treatment have been investigated using Monte Carlo (MC) simulations and experimental methods. The 28 cm long applicator has a flexible structure made of silicone rubber for easy passage into cavities with deep-seated tumors. It consists of eight source catheters arranged around a central cavity for shielding insertion, and is compatible for use with an endocavitary balloon. A phase space model of the HDR source has been validated for dose calculations using the GEANT4 MC code. GAFCHROMIC EBT model film was used to measure dose distributions in water around shielded and unshielded applicators with two loading configurations, and to quantify the shielding effect of a balloon injected with an iodine solution (300 mg I/mL). The film calibration procedure was performed in water using an 192Ir HDR source. Ionization chamber measurements in a Lucite phantom show that placing a tungsten rod in the applicator attenuates the dose in the shielded region by up to 85%. Inserting the shielded applicator into a water-filled balloon pushes the neighboring tissues away from the radiation source, and the resulting geometric displacement reduces the dose by up to 53%; another 8% dose reduction can be achieved when the balloon is injected with an iodine solution. All experimental results agree with the GEANT4 calculations within measurement uncertainties. PMID:17278803

  16. Dosimetric characterization of a novel intracavitary mold applicator for {sup 192}Ir high dose rate endorectal brachytherapy treatment

    SciTech Connect

    Poon, Emily; Reniers, Brigitte; Devic, Slobodan; Vuong, Te; Verhaegen, Frank

    2006-12-15

    The dosimetric properties of a novel intracavitary mold applicator for {sup 192}Ir high dose rate (HDR) endorectal cancer treatment have been investigated using Monte Carlo (MC) simulations and experimental methods. The 28 cm long applicator has a flexible structure made of silicone rubber for easy passage into cavities with deep-seated tumors. It consists of eight source catheters arranged around a central cavity for shielding insertion, and is compatible for use with an endocavitary balloon. A phase space model of the HDR source has been validated for dose calculations using the GEANT4 MC code. GAFCHROMIC trade mark sign EBT model film was used to measure dose distributions in water around shielded and unshielded applicators with two loading configurations, and to quantify the shielding effect of a balloon injected with an iodine solution (300 mg I/mL). The film calibration procedure was performed in water using an {sup 192}Ir HDR source. Ionization chamber measurements in a Lucite phantom show that placing a tungsten rod in the applicator attenuates the dose in the shielded region by up to 85%. Inserting the shielded applicator into a water-filled balloon pushes the neighboring tissues away from the radiation source, and the resulting geometric displacement reduces the dose by up to 53%; another 8% dose reduction can be achieved when the balloon is injected with an iodine solution. All experimental results agree with the GEANT4 calculations within measurement uncertainties.

  17. SU-E-T-118: Dose Verification for Accuboost Applicators Using TLD, Ion Chamber and Gafchromic Film Measurements

    SciTech Connect

    Chisela, W; Yao, R; Dorbu, G

    2014-06-01

    Purpose: To verify dose delivered with HDR Accuboost applicators using TLD, ion chamber and Gafchromic film measurements and to examine applicator leakage. Methods: A microSelectron HDR unit was used to deliver a dose of 50cGy to the mid-plane of a 62mm thick solid water phantom using dwell times from Monte Carlo pre-calculated nomograms for a 60mm, 70mm Round and 60mm Skin-Dose Optimized (SDO) applicators respectively. GafChromic EBT3+ film was embedded in the phantom midplane horizontally to measure dose distribution. Absolute dose was also measured with TLDs and an ADCL calibrated parallel-plate ion chamber placed in the film plane at field center for each applicator. The film was calibrated using 6MV x-ray beam. TLDs were calibrated in a Cs-137 source at UW-Madison calibration laboratory. Radiation leakage through the tungsten alloy shell was measured with a film wrapped around outside surface of a 60mm Round applicator. Results: Measured maximum doses at field center are consistently lower than predicated by 5.8% for TLD, 8.8% for ion chamber, and 2.6% for EBT3+ film on average, with measurement uncertainties of 2.2%, 0.3%, and 2.9% for TLD, chamber, film respectively. The total standard uncertainties for ion chamber and Gafchromic film measurement are 4.9% and 4.6% respectively[1]. The area defined by the applicator aperture was covered by 80% of maximum dose for 62mm compression thickness. When 100cGy is delivered to mid-plane with a 60mm Round applicator, surface dose ranges from 60cGy to a maximum of 145cGy, which occurs at source entrance to the applicator. Conclusion: Measured doses by all three techniques are consistently lower than predicted in our measurements. For a compression thickness of 62 mm, the field size defined by the applicator is only covered by 80% of prescribed dose. Radiation leakage of up to 145cGy was found at the source entrance of applicators.

  18. Development and application of a random lung model for dose calculations in radiotherapy

    NASA Astrophysics Data System (ADS)

    Liang, Liang

    that occur in approximate clinical dose calculation methods. Finally, we address potential improvements for our random lung model and some possible future applications.

  19. Deformable 3D-2D registration for CT and its application to low dose tomographic fluoroscopy

    NASA Astrophysics Data System (ADS)

    Flach, Barbara; Brehm, Marcus; Sawall, Stefan; Kachelrieß, Marc

    2014-12-01

    Many applications in medical imaging include image registration for matching of images from the same or different modalities. In the case of full data sampling, the respective reconstructed images are usually of such a good image quality that standard deformable volume-to-volume (3D-3D) registration approaches can be applied. But research in temporal-correlated image reconstruction and dose reductions increases the number of cases where rawdata are available from only few projection angles. Here, deteriorated image quality leads to non-acceptable deformable volume-to-volume registration results. Therefore a registration approach is required that is robust against a decreasing number of projections defining the target position. We propose a deformable volume-to-rawdata (3D-2D) registration method that aims at finding a displacement vector field maximizing the alignment of a CT volume and the acquired rawdata based on the sum of squared differences in rawdata domain. The registration is constrained by a regularization term in accordance with a fluid-based diffusion. Both cost function components, the rawdata fidelity and the regularization term, are optimized in an alternating manner. The matching criterion is optimized by a conjugate gradient descent for nonlinear functions, while the regularization is realized by convolution of the vector fields with Gaussian kernels. We validate the proposed method and compare it to the demons algorithm, a well-known 3D-3D registration method. The comparison is done for a range of 4-60 target projections using datasets from low dose tomographic fluoroscopy as an application example. The results show a high correlation to the ground truth target position without introducing artifacts even in the case of very few projections. In particular the matching in the rawdata domain is improved compared to the 3D-3D registration for the investigated range. The proposed volume-to-rawdata registration increases the robustness regarding sparse

  20. Deformable 3D-2D registration for CT and its application to low dose tomographic fluoroscopy.

    PubMed

    Flach, Barbara; Brehm, Marcus; Sawall, Stefan; Kachelrieß, Marc

    2014-12-21

    Many applications in medical imaging include image registration for matching of images from the same or different modalities. In the case of full data sampling, the respective reconstructed images are usually of such a good image quality that standard deformable volume-to-volume (3D-3D) registration approaches can be applied. But research in temporal-correlated image reconstruction and dose reductions increases the number of cases where rawdata are available from only few projection angles. Here, deteriorated image quality leads to non-acceptable deformable volume-to-volume registration results. Therefore a registration approach is required that is robust against a decreasing number of projections defining the target position. We propose a deformable volume-to-rawdata (3D-2D) registration method that aims at finding a displacement vector field maximizing the alignment of a CT volume and the acquired rawdata based on the sum of squared differences in rawdata domain. The registration is constrained by a regularization term in accordance with a fluid-based diffusion. Both cost function components, the rawdata fidelity and the regularization term, are optimized in an alternating manner. The matching criterion is optimized by a conjugate gradient descent for nonlinear functions, while the regularization is realized by convolution of the vector fields with Gaussian kernels. We validate the proposed method and compare it to the demons algorithm, a well-known 3D-3D registration method. The comparison is done for a range of 4-60 target projections using datasets from low dose tomographic fluoroscopy as an application example. The results show a high correlation to the ground truth target position without introducing artifacts even in the case of very few projections. In particular the matching in the rawdata domain is improved compared to the 3D-3D registration for the investigated range. The proposed volume-to-rawdata registration increases the robustness regarding sparse

  1. Dose and cycle of insecticide applications in the control of malaria

    PubMed Central

    Macdonald, G.; Davidson, G.

    1953-01-01

    The authors first review the doses and cycles of application normally recommended in different parts of the world for DDT, BHC, and dieldrin in controlling malaria, and then discuss the experimental evidence concerning their actual efficacy in the field. The irritant effect of the various insecticides is compared, DDT being found the most irritant and dieldrin the least. BHC appears to be highly irritant when solid, but not when vaporized. The problem of the application of residual insecticides to absorbent surfaces, such as mud, is considered; the wettable powders are generally accepted as the most efficient formulation for such surfaces, but even with these a marked loss in toxicity may occur, requiring higher initial doses and more frequent application than on non-absorbent surfaces. With volatile insecticides, such as BHC, some degree of absorption slows down the loss by volatilization, but at the usual field dosages of 0.1 g and 0.2 g of gamma-BHC per m2 the decline in toxicity is still rapid. Experiments have also shown that mixtures of DDT and BHC may, in some circumstances, combine the initial high kill of the latter with the persistent moderate kill of the former. Considering the insecticidal efficiency needed for the control of malaria, the authors find that most natural circumstances would be met by attaining a mortality-rate of about 65% of mosquitos entering treated shelters; 85% mortality would be suitable for the most severe conditions and 65% mortality for controlling moderate transmission by endophilic mosquitos. PMID:13141131

  2. Lethality of Suicide Attempt Rating Scale.

    ERIC Educational Resources Information Center

    Smith, K.; And Others

    1984-01-01

    Presents an 11-point scale for measuring the degree of lethality of suicide attempts. The scale has nine example "anchors" and uses the relative lethality of an extensive table of drugs. The scale can be used reliably by nonmedical personnel with no prior training. (Author/BL)

  3. Alcohol Consumption and Nearly Lethal Suicide Attempts.

    ERIC Educational Resources Information Center

    Powell, Kenneth E.; Kresnow, Marcie-jo; Mercy, James A.; Potter, Lloyd B.; Swann, Alan C.; Frankowski, Ralph F.; Lee, Roberta K.; Bayer, Timothy L.

    2002-01-01

    Presents a case-control study of the association between nearly lethal suicide attempts and facets of alcohol consumption; namely, drinking frequency, drinking quantity, binge drinking, alcoholism, drinking within 3 hours of suicide attempt, and age began drinking. In bivariate analyses, all measures were associated with nearly lethal suicide…

  4. Potentiation by caffeine of potentially lethal fast-neutron damage in cultured human cells

    SciTech Connect

    Schroy, C.B.; Furcinitti, P.S.; Todd, P.; Kukulinsky, N.E.

    1980-11-01

    Caffeine was found to potentiate single-dose fast-neutron-induced killing of human T-1 cells when present at 2 mM for 60 hr or more after (and 10 hr before) irradiation. Analyses of survival curves of cells treated with neutrons or X rays with and without caffeine indicate that only the linear, low-dose portion of survival curves is modified. Potentiation of lethality by caffeine is attributed mainly to its effects on single-hit potentially lethal lesions, possibly certain DNA double-strand breaks.

  5. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction.

    PubMed

    Ahmad, Ijaz; Huang, Lingli; Hao, Haihong; Sanders, Pascal; Yuan, Zonghui

    2016-01-01

    Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model. PMID:26989688

  6. Analysis and comparison of sigmoidal curves: application to dose-response data.

    PubMed

    Meddings, J B; Scott, R B; Fick, G H

    1989-12-01

    A number of physiological or pharmacological studies generate sigmoidal dose-response curves. Ideally, data analysis should provide numerical solutions for curve parameters. In addition, for curves obtained under different experimental conditions, testing for significant differences should be easily performed. We have reviewed the literature over the past 3 years in six journals publishing papers in the field of gastrointestinal physiology and established the curve analysis technique used in each. Using simulated experimental data of known error structure, we have compared these techniques with nonlinear regression analysis. In terms of their ability to provide accurate estimates of ED50 and maximal response, none approached the accuracy and precision of nonlinear regression. This technique is as easily performed as the classic methods and additionally provides an opportunity for rigorous statistical analysis of data. We present a method of determining the significance of differences found in the ED50 and maximal response under different experimental conditions. The method is versatile and applicable to a variety of different physiological and pharmacological dose-response curves. PMID:2610264

  7. Practical experience of the application of ICRP models in internal dose assessment.

    PubMed

    Peace, M S

    2003-01-01

    The introduction of the Ionising Radiations Regulations 1999 in the UK, which came into force on 1 January 2000, led to significant changes in internal dose assessment. Before this date, assessments were based on the methodology from ICRP Publication 26 and, in general, made use of simple models such as those detailed in ICRP Publication 30. However, the introduction of the new Regulations required the use of ICRP Publication 60 methodology, and, at the same time, the latest ICRP biokinetic models were introduced. Many of these newer models were considerably more complex than the ones they replaced. In particular, the use of 'recycling', where activity is constantly recirculated between different organs, meant that the models could not simply be implemented by use of the Skrable formula, as detailed in ICRP Publication 30. This paper outlines two aspects of the application of these latest ICRP models. First, the problems encountered during implementation of these models are detailed, and secondly, it covers the practical experience of using the resulting computer programs for internal dose assessment. PMID:14526923

  8. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    PubMed Central

    Ahmad, Ijaz; Huang, Lingli; Hao, Haihong; Sanders, Pascal; Yuan, Zonghui

    2016-01-01

    Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model. PMID:26989688

  9. Application of RADTRAN to estimation of doses to persons in enclosed spaces

    SciTech Connect

    Neuhauser, K. S.

    1992-01-01

    The RADTRAN computer code for transportation risk analysis can be used to estimate doses to persons in enclosed volumes. This application was developed in response to a need to examine consequences of a hypothetical container leak during accident-free transportation by cargo air. The original problem addressed tritium containers, but the method can be applied to any gaseous or suspended particulate material potentially released in an airplane or other enclosed area (e.g., warehouse) under accident-free conditions. Such leakage can occur during shipment of any radioactive gas or material with a gaseous phase. Atmospheric dispersion is normally modeled in RADTRAN as a series of downwind isopleths each of which is assigned a dilution factor (also known as time-integrated concentration or X/Q value). These values are located in look-up tables in RADTRAN and are normally taken from externally performed Gaussian dispersion calculations. The dilution factors are used to estimate inhalation dose to persons in the specified downwind areas.

  10. Application of GEANT4 radiation transport toolkit to dose calculations in anthropomorphic phantoms.

    PubMed

    Rodrigues, P; Trindade, A; Peralta, L; Alves, C; Chaves, A; Lopes, M C

    2004-12-01

    In this paper, we present a novel implementation of a dose calculation application, based on the GEANT4 Monte Carlo toolkit. Validation studies were performed with an homogeneous water phantom and an Alderson-Rando anthropomorphic phantom both irradiated with high-energy photon beams produced by a clinical linear accelerator. As input, this tool requires computer tomography images for automatic codification of voxel-based geometries and phase-space distributions to characterize the incident radiation field. Simulation results were compared with ionization chamber, thermoluminescent dosimetry data and commercial treatment planning system calculations. In homogeneous water phantom, overall agreement with measurements were within 1-2%. For anthropomorphic simulated setups (thorax and head irradiation) mean differences between GEANT4 and TLD measurements were less than 2%. Significant differences between GEANT4 and a semi-analytical algorithm implemented in the treatment planning system, were found in low-density regions, such as air cavities with strong electronic disequilibrium. PMID:15388147

  11. Dose Tracker Application for Monitoring Crew Medication Usage, Symptoms, and Adverse Effects During Missions

    NASA Technical Reports Server (NTRS)

    Wotring, Virginia; Smith, LaRona

    2015-01-01

    Medication usage records can be used as a relatively nonintrusive means of monitoring health. This has been attempted previously through crew medical records, but these records are incomplete from the perspective of a research pharmacologist. During the shuttle era, NASA operations did not include routine questioning of crewmembers about their medication use until after missions were complete. The (long!) questionnaire was on paper. Asking crewmembers to recall medication use from weeks before questioning made getting complete and accurate information virtually impossible. This study will document medication usage of crewmembers before and during their missions. It will capture previously unrecorded data regarding medication use during spaceflight, including side effect qualities, frequencies and severities. The research-oriented data will be collected for research purposes, separate from medical records. Dose Tracker employs an iOS application (app) for fast & easy collection of medication usage data from crewmember participants during their missions.

  12. Low dose daily rhGM-CSF application activates monocytes and dendritic cells in vivo.

    PubMed

    Demir, Gokhan; Klein, Hans Otto; Tuzuner, Nukhet

    2003-12-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is a powerful cytokine with multiple actions. We investigated the effects of low dose daily rhGM-CSF application on monocytes and peripheral circulating dendritic cells (DC) in malignant melanoma patients in vivo. Twenty patients were included; rhGM-CSF was given as daily subcutaneous injections for 14 days. A significant increase was noted in monocytes and granulocytes, starting on the 5th day. Expression of CD95 (Apo-1/Fas) and CD45RO on monocytes increased significantly on the 5th day, and CD4 expression on monocytes increased significantly on the 14th day. Peripheral circulating dendritic cells which were 0.94% in the beginning, increased to 1.35% (P<0.04) and to 1.96% (P<0.001) on days 5 and 14, respectively. PMID:12921948

  13. Lethal photosensitization of Helicobacter species

    NASA Astrophysics Data System (ADS)

    Millson, Charles E.; Wilson, Michael; MacRobert, Alexander J.; Thurrell, Wendy; Mlkvy, Peter; Davies, Claire; Bown, Stephen G.

    1995-01-01

    Helicobacter pylori (H. pylori) is associated with a large number of gastroduodenal disorders. Clearance of the bacteria has been shown to benefit patients with duodenal ulcers, gastric ulcers, and certain rare types of gastric tumors. Broad-spectrum antibiotics are the mainstay of current treatment strategies but side-effects, poor compliance, and drug resistance limit their usefulness. We sensitized H. pylori with toluidine blue, haematoporphyrin derivative, aluminum disulphonated phthalocyanine, methylene blue or protoporphyrin IX prior to exposure to low-power laser light from either a gallium aluminum arsenide laser or a helium neon gas laser. All 5 sensitizers caused reductions of greater than 1000-fold in the number of viable bacteria. Light alone had no effect and only HpD caused a significant decrease in bacterial numbers without laser light. Next, we sensitized H. mustelae on explanted ferret gastric mucosa (ex vivo) with the same sensitizers and exposed them to light from a copper vapor pumped dye laser tuned appropriately. MB caused significant reductions in bacterial counts. Successful lethal photosensitization of Helicobacter pylori both in vitro and ex vivo raises the possibility of a local method for eradicating the bacteria, especially as the bacteria are only found in those parts of the upper gastrointestinal tract that are accessible to the endoscope.

  14. Lethal outcome in xanthogranulomatous endometritis.

    PubMed

    Noack, Frank; Briese, Juliane; Stellmacher, Florian; Hornung, Daniela; Horny, Hans-Peter

    2006-05-01

    Xanthogranulomatous inflammation is rare, mainly involving the kidneys, while primary xanthogranulomatous endometritis (XE) is a very unusual finding, histologically characterized by partial or complete replacement of the mucosa by granulation tissue with an abundance of foamy histiocytes, siderophages and multinucleated giant cells. We present the case of a 69-year-old woman with a short history of abdominal pain and a palpable mass in the pouch of Douglas. Dilatation of the cervix drained a pyometra. Histological examination of the curettage rendered the diagnosis of XE. Microbiological studies revealed enterococcus spp. and Peptostreptococcus magnus. Despite antibiotic treatment the patient died of heart failure due to systemic inflammation. Autopsy confirmed the diagnosis of XE with transmural extension into the peritoneal cavity. Such a lethal course of XE is extraordinary. Proposed causes of XE include obstruction, infection and hemorrhage. Demonstration of enterococcus spp. and P. magnus supports the probable significance of bacteria in the development of XE. Because this condition may mimic malignant disease macroscopically and histologically, knowledge of XE is of major importance for both pathologists and gynecologists. PMID:16725016

  15. Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

    PubMed Central

    Vogel, Alexander J.; Harris, Seth; Marsteller, Nathan; Condon, Shirley A.

    2014-01-01

    Abstract Infection with influenza A virus (IAV) leads to acute lung injury and possibly fatal complications, especially in immunocompromised, elderly, or chronically infected individuals. Therefore, it is important to study the factors that lead to pathology and mortality in infected hosts. In this report, we analyze immune responses to infection at a sublethal (0.1 LD50) and lethal (1 LD50) dose of the highly pathogenic IAV A/Puerto Rico/8/34 (PR8). Our experiments revealed that infection with a 1 LD50 dose induced peak viral titers at day 2 compared to day 4 in the 0.1 LD50 dose. Moreover, early cytokine dysregulation was observed in the lethal dose with significantly elevated levels of IFN-α, TNF-α, CXCL9, IL-6, and MCP-1 produced at day 2. Early inflammatory responses following infection with 1 LD50 correlated with a greater influx of neutrophils into the lung. However, depletion of neutrophils enhanced morbidity following IAV infection. Though no differences in CD8+ cell function were observed, CD4+ effector responses were impaired in the lungs 8 days after infection with 1 LD50. Histological analysis revealed significant pathology in lethally infected mice at day 2 and day 6 postinfection, when viral titers remained high. Treating lethally infected mice with oseltamivir inhibited viral titers to sublethal levels, and abrogated the pathology associated with the lethal dose. Together, these results suggest that early cytokine dysregulation and viral replication play a role in pulmonary damage and high mortality in lethally infected mice. PMID:24787235

  16. Dosimetry in radiotherapy using a-Si EPIDs: Systems, methods, and applications focusing on 3D patient dose estimation

    NASA Astrophysics Data System (ADS)

    McCurdy, B. M. C.

    2013-06-01

    An overview is provided of the use of amorphous silicon electronic portal imaging devices (EPIDs) for dosimetric purposes in radiation therapy, focusing on 3D patient dose estimation. EPIDs were originally developed to provide on-treatment radiological imaging to assist with patient setup, but there has also been a natural interest in using them as dosimeters since they use the megavoltage therapy beam to form images. The current generation of clinically available EPID technology, amorphous-silicon (a-Si) flat panel imagers, possess many characteristics that make them much better suited to dosimetric applications than earlier EPID technologies. Features such as linearity with dose/dose rate, high spatial resolution, realtime capability, minimal optical glare, and digital operation combine with the convenience of a compact, retractable detector system directly mounted on the linear accelerator to provide a system that is well-suited to dosimetric applications. This review will discuss clinically available a-Si EPID systems, highlighting dosimetric characteristics and remaining limitations. Methods for using EPIDs in dosimetry applications will be discussed. Dosimetric applications using a-Si EPIDs to estimate three-dimensional dose in the patient during treatment will be overviewed. Clinics throughout the world are implementing increasingly complex treatments such as dynamic intensity modulated radiation therapy and volumetric modulated arc therapy, as well as specialized treatment techniques using large doses per fraction and short treatment courses (ie. hypofractionation and stereotactic radiosurgery). These factors drive the continued strong interest in using EPIDs as dosimeters for patient treatment verification.

  17. Three-dimensional dose verification of the clinical application of gamma knife stereotactic radiosurgery using polymer gel and MRI

    NASA Astrophysics Data System (ADS)

    Papagiannis, P.; Karaiskos, P.; Kozicki, M.; Rosiak, J. M.; Sakelliou, L.; Sandilos, P.; Seimenis, I.; Torrens, M.

    2005-05-01

    This work seeks to verify multi-shot clinical applications of stereotactic radiosurgery with a Leksell Gamma Knife model C unit employing a polymer gel-MRI based experimental procedure, which has already been shown to be capable of verifying the precision and accuracy of dose delivery in single-shot gamma knife applications. The treatment plan studied in the present work resembles a clinical treatment case of pituitary adenoma using four 8 mm and one 14 mm collimator helmet shots to deliver a prescription dose of 15 Gy to the 50% isodose line (30 Gy maximum dose). For the experimental dose verification of the treatment plan, the same criteria as those used in the clinical treatment planning evaluation were employed. These included comparison of measured and GammaPlan calculated data, in terms of percentage isodose contours on axial, coronal and sagittal planes, as well as 3D plan evaluation criteria such as dose-volume histograms for the target volume, target coverage and conformity indices. Measured percentage isodose contours compared favourably with calculated ones despite individual point fluctuations at low dose contours (e.g., 20%) mainly due to the effect of T2 measurement uncertainty on dose resolution. Dose-volume histogram data were also found in a good agreement while the experimental results for the percentage target coverage and conformity index were 94% and 1.17 relative to corresponding GammaPlan calculations of 96% and 1.12, respectively. Overall, polymer gel results verified the planned dose distribution within experimental uncertainties and uncertainty related to the digitization process of selected GammaPlan output data.

  18. Preclinical dose number and its application in understanding drug absorption risk and formulation design for preclinical species.

    PubMed

    Wuelfing, W Peter; Daublain, Pierre; Kesisoglou, Filippos; Templeton, Allen; McGregor, Caroline

    2015-04-01

    In the drug discovery setting, the ability to rapidly identify drug absorption risk in preclinical species at high doses from easily measured physical properties is desired. This is due to the large number of molecules being evaluated and their high attrition rate, which make resource-intensive in vitro and in silico evaluation unattractive. High-dose in vivo data from rat, dog, and monkey are analyzed here, using a preclinical dose number (PDo) concept based on the dose number described by Amidon and other authors (Pharm. Res., 1993, 10, 264-270). PDo, as described in this article, is simply calculated as dose (mg/kg) divided by compound solubility in FaSSIF (mg/mL) and approximates the volume of biorelevant media per kilogram of animal that would be needed to fully dissolve the dose. High PDo values were found to be predictive of difficulty in achieving drug exposure (AUC)-dose proportionality in in vivo studies, as could be expected; however, this work analyzes a large data set (>900 data points) and provides quantitative guidance to identify drug absorption risk in preclinical species based on a single solubility measurement commonly carried out in drug discovery. Above the PDo values defined, >50% of all in vivo studies exhibited poor AUC-dose proportionality in rat, dog, and monkey, and these values can be utilized as general guidelines in discovery and early development to rapidly assess risk of solubility-limited absorption for a given compound. A preclinical dose number generated by biorelevant dilutions of formulated compounds (formulated PDo) was also evaluated and defines solubility targets predictive of suitable AUC-dose proportionality in formulation development efforts. Application of these guidelines can serve to efficiently identify compounds in discovery that are likely to present extreme challenges with respect to solubility-limited absorption in preclinical species as well as reduce the testing of poor formulations in vivo, which is a key

  19. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    PubMed

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX. PMID:26621540

  20. A dose computation model for sup 241 Am vaginal applicators including the source-to-source shielding effects

    SciTech Connect

    Nath, R.; Park, C.H.; King, C.R.; Muench, P. )

    1990-09-01

    A dose computation model has been developed for the determination of dose distributions around vaginal plaque applicators containing encapsulated {sup 241}Am sources. Encapsulated sources of {sup 241}Am emit primarily 60-keV photons which have a half-value layer thickness of 1/8 mm of lead. This makes possible highly effective {ital in} {ital vivo} shielding of normal tissues at risk, by placing thin lead shields at appropriate places on the applicator. However, self-absorption of photons in the source material itself is intense, requiring bulky sources of about 1 cm diameter. These sources also produce considerable source-to-source shielding which must be taken into account in dose calculations. Our dose computation model for a single source employs three-dimensional integration of dose contributions from volume elements of the source including the effects of absorption and scattering of photons in the source material, titanium encapsulation, and water. An empirical correction to Berger's data on buildup factors of point, isotropic sources is made to account for the effects of anisotropic photon emission by cylindrical {sup 241}Am sources. The second part of our dose computation model takes into account source-to-source shielding effects on both primary and scattered photons for the vaginal plaque geometry. The results of the model have been verified for accuracy by comparisons with extensive dosimetry measurements using lithium fluoride thermoluminescent dosimeters.

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

    PubMed

    Harrison, J D; Streffer, C

    2007-01-01

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

  2. Methods of space radiation dose analysis with applications to manned space systems

    NASA Technical Reports Server (NTRS)

    Langley, R. W.; Billings, M. P.

    1972-01-01

    The full potential of state-of-the-art space radiation dose analysis for manned missions has not been exploited. Point doses have been overemphasized, and the critical dose to the bone marrow has been only crudely approximated, despite the existence of detailed man models and computer codes for dose integration in complex geometries. The method presented makes it practical to account for the geometrical detail of the astronaut as well as the vehicle. Discussed are the major assumptions involved and the concept of applying the results of detailed proton dose analysis to the real-time interpretation of on-board dosimetric measurements.

  3. Inhalation reference dose (RfDi): an application of interspecies dosimetry modeling for risk assessment of insoluble particles.

    PubMed

    Jarabek, A M; Menache, M G; Overton, J H; Dourson, M L; Miller, F J

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses [the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity] for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. Predictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated (Overton and Miller 1988). Models that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. This paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The ratio of these two values serves as a scaling factor that can be applied in the R f D methodology to account for the dosimetric differences in the inhaled deposited dose. This application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation. PMID:2606680

  4. Inhalation reference dose (RfDi): An application of interspecies dosimetry modeling for risk assessment of insoluble particles

    SciTech Connect

    Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.; Dourson, M.L.; Miller, F.J. )

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses (the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity) for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. Predictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated. Models that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. This paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The ratio of these two values serves as a scaling factor that can be applied in the R f D methodology to account for the dosimetric differences in the inhaled deposited dose. This application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

  5. Enhanced inactivation of Escherichia coli and Listeria monocytogenes by exposure to 405 nm light under sub-lethal temperature, salt and acid stress conditions.

    PubMed

    McKenzie, Karen; Maclean, Michelle; Timoshkin, Igor V; MacGregor, Scott J; Anderson, John G

    2014-01-17

    The antimicrobial effects of 405 nm light have generated interest in its use as an emerging disinfection technology with potential food-related applications. The aim of this study was to assess the bactericidal efficacy of 405 nm light for inactivation of Escherichia coli and Listeria monocytogenes under sub-lethally stressed environmental conditions. Bacteria were exposed to 405 nm light from a light emitting diode (LED) array under various temperature, salt (NaCl) and acid conditions to determine if bacterial susceptibility to 405 nm light inactivation is affected when exposed under these conditions. Non-stressed bacterial populations (10(5) CFU/mL) were exposed to increasing doses of 405 nm light (~70 mW/cm(2)) and the inactivation results were compared with those generated under stress conditions. Bacteria were held at various temperatures (4°C, 22°C and 45°C), acid concentrations (pH3, 3.5 and 7) and salt concentrations (0%, 0.8%, 10% and 15% NaCl), and simultaneously exposed to 405 nm light. Enhanced inactivation of both E. coli and L. monocytogenes was achieved when light exposure was combined with each of the sub-lethal stresses, with significantly increased inactivation rates compared to non-stressed populations (P≤0.05). One exception was with L. monocytogenes when light-exposed in the presence of 15% salt, as this combination reduced bacterial inactivation. The greatest enhancement of 405 nm light inactivation for both bacterial species was achieved when light exposure was combined with sub-lethal acid stress conditions at pH3. This was demonstrated by a 5-log10 reduction of E. coli following a 405 nm light dose of 84 J/cm(2) compared to 378 J/cm(2) for non-stressed populations (77% reduction in dose) and by a 5-log10 reduction of L. monocytogenes achieved with a dose of 42 J/cm(2) which corresponded to 50% of the dose required for the equivalent reduction of non-stressed populations. This acid-enhanced 405 nm light inactivation effect was

  6. Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with 131I-mIBG

    NASA Astrophysics Data System (ADS)

    Mínguez, Pablo; Gustafsson, Johan; Flux, Glenn; Sjögreen Gleisner, Katarina

    2016-03-01

    In this work, the biologically effective dose (BED) is investigated for fractionated molecular radiotherapy (MRT). A formula for the Lea-Catcheside G-factor is derived which takes the possibility of combinations of sub-lethal damage due to radiation from different administrations of activity into account. In contrast to the previous formula, the new G-factor has an explicit dependence on the time interval between administrations. The BED of tumour and liver is analysed in MRT of neuroblastoma with 131I-mIBG, following a common two-administration protocol with a mass-based activity prescription. A BED analysis is also made for modified schedules, when due to local regulations there is a maximum permitted activity for each administration. Modifications include both the simplistic approach of delivering this maximum permitted activity in each of the two administrations, and also the introduction of additional administrations while maintaining the protocol-prescribed total activity. For the cases studied with additional (i.e. more than two) administrations, BED of tumour and liver decreases at most 12% and 29%, respectively. The decrease in BED of the tumour is however modest compared to the two-administration schedule using the maximum permitted activity, where the decrease compared to the original schedule is 47%.

  7. Using rule-based shot dose assignment in model-based MPC applications

    NASA Astrophysics Data System (ADS)

    Bork, Ingo; Buck, Peter; Wang, Lin; Müller, Uwe

    2014-10-01

    Shrinking feature sizes and the need for tighter CD (Critical Dimension) control require the introduction of new technologies in mask making processes. One of those methods is the dose assignment of individual shots on VSB (Variable Shaped Beam) mask writers to compensate CD non-linearity effects and improve dose edge slope. Using increased dose levels only for most critical features, generally only for the smallest CDs on a mask, the change in mask write time is minimal while the increase in image quality can be significant. This paper describes a method combining rule-based shot dose assignment with model-based shot size correction. This combination proves to be very efficient in correcting mask linearity errors while also improving dose edge slope of small features. Shot dose assignment is based on tables assigning certain dose levels to a range of feature sizes. The dose to feature size assignment is derived from mask measurements in such a way that shape corrections are kept to a minimum. For example, if a 50nm drawn line on mask results in a 45nm chrome line using nominal dose, a dose level is chosen which is closest to getting the line back on target. Since CD non-linearity is different for lines, line-ends and contacts, different tables are generated for the different shape categories. The actual dose assignment is done via DRC rules in a pre-processing step before executing the shape correction in the MPC engine. Dose assignment to line ends can be restricted to critical line/space dimensions since it might not be required for all line ends. In addition, adding dose assignment to a wide range of line ends might increase shot count which is undesirable. The dose assignment algorithm is very flexible and can be adjusted based on the type of layer and the best balance between accuracy and shot count. These methods can be optimized for the number of dose levels available for specific mask writers. The MPC engine now needs to be able to handle different dose

  8. Spot scanning proton therapy plan assessment: design and development of a dose verification application for use in routine clinical practice

    NASA Astrophysics Data System (ADS)

    Augustine, Kurt E.; Walsh, Timothy J.; Beltran, Chris J.; Stoker, Joshua B.; Mundy, Daniel W.; Parry, Mark D.; Bues, Martin; Fatyga, Mirek

    2016-04-01

    The use of radiation therapy for the treatment of cancer has been carried out clinically since the late 1800's. Early on however, it was discovered that a radiation dose sufficient to destroy cancer cells can also cause severe injury to surrounding healthy tissue. Radiation oncologists continually strive to find the perfect balance between a dose high enough to destroy the cancer and one that avoids damage to healthy organs. Spot scanning or "pencil beam" proton radiotherapy offers another option to improve on this. Unlike traditional photon therapy, proton beams stop in the target tissue, thus better sparing all organs beyond the targeted tumor. In addition, the beams are far narrower and thus can be more precisely "painted" onto the tumor, avoiding exposure to surrounding healthy tissue. To safely treat patients with proton beam radiotherapy, dose verification should be carried out for each plan prior to treatment. Proton dose verification systems are not currently commercially available so the Department of Radiation Oncology at the Mayo Clinic developed its own, called DOSeCHECK, which offers two distinct dose simulation methods: GPU-based Monte Carlo and CPU-based analytical. The three major components of the system include the web-based user interface, the Linux-based dose verification simulation engines, and the supporting services and components. The architecture integrates multiple applications, libraries, platforms, programming languages, and communication protocols and was successfully deployed in time for Mayo Clinic's first proton beam therapy patient. Having a simple, efficient application for dose verification greatly reduces staff workload and provides additional quality assurance, ultimately improving patient safety.

  9. 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality

    PubMed Central

    Hohmann, Miriam S. N.; Cardoso, Renato D. R.; Pinho-Ribeiro, Felipe A.; Crespigio, Jefferson; Cunha, Thiago M.; Alves-Filho, José C.; da Silva, Rosiane V.; Pinge-Filho, Phileno; Ferreira, Sergio H.; Cunha, Fernando Q.; Casagrande, Rubia; Verri, Waldiceu A.

    2013-01-01

    5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO−/−) mice and background wild type mice were challenged with APAP (0.3–6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO−/− mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO−/− mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage. PMID:24288682

  10. Development of Synthetic Lethality Anticancer Therapeutics

    PubMed Central

    2015-01-01

    The concept of synthetic lethality (the creation of a lethal phenotype from the combined effects of mutations in two or more genes) has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics. These efforts include screening for novel anticancer agents, identifying novel therapeutic targets, characterizing mechanisms of resistance to targeted therapy, and improving efficacies through the rational design of combination therapy. This review discusses recent developments in synthetic lethality anticancer therapeutics, including poly ADP-ribose polymerase inhibitors for BRCA1- and BRCA2-mutant cancers, checkpoint inhibitors for p53 mutant cancers, and small molecule agents targeting RAS gene mutant cancers. Because cancers are caused by mutations in multiple genes and abnormalities in multiple signaling pathways, synthetic lethality for a specific tumor suppressor gene or oncogene is likely cell context-dependent. Delineation of the mechanisms underlying synthetic lethality and identification of treatment response biomarkers will be critical for the success of synthetic lethality anticancer therapy. PMID:24893124

  11. Application of Physiologically Based Pharmacokinetic (PBPK) Modeling to Support Dose Selection: Report of an FDA Public Workshop on PBPK

    PubMed Central

    Wagner, C; Zhao, P; Pan, Y; Hsu, V; Grillo, J; Huang, SM; Sinha, V

    2015-01-01

    The US Food and Drug Administration (FDA) public workshop, entitled “Application of Physiologically-based Pharmacokinetic (PBPK) Modeling to Support Dose Selection focused on the role of PBPK in drug development and regulation. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary and panel discussions. This report summarizes the discussions and provides current perspectives on the application of PBPK in different areas, including its utility, predictive performance, and reporting for regulatory submissions. PMID:26225246

  12. Application of urea dosing for alkalinity supply during anaerobic digestion of vinasse.

    PubMed

    Boncz, M A; Formagini, E L; Santos, L da S; Marques, R D; Paulo, P L

    2012-01-01

    Pushed by demand for renewable energy, the ethanol industry in Brazil is expanding. However, production of 1 m(3) of ethanol generates around 13 m(3) of liquid residues (vinasse), so this expansion results in an increasing need for a more adequate destination of these residues. Nowadays the vinasse is dispersed on the sugar cane fields in the practice of fertirrigation, but anaerobic digestion of this residue may be a better solution, additionally offering an alternative source of energy, able to complement hydroelectric power supply in the dry season. However, when trying to digest vinasse at reduced hydraulic retention times, complications arise from its strong tendency toward acidification, upsetting the fragile balance of transformations normally occurring under anaerobic conditions. For successful operation of an anaerobic treatment process with acceptable hydraulic residence times, increasing alkalinity levels inside the reactor is neces-sary. In the present work we show that pH regulation by means of urea dosing, in spite of the risk posed by ammonia toxicity towards methanogenic biomass, can be a viable alternative to avoid vinasse acidification. The ammonia formed in urea conversion remains in solution, rather than escaping to the biogas, and so its use as fertiliser can offset its cost of application in the process. PMID:23032778

  13. Accidental gamma dose measurement using commercial glasses.

    PubMed

    Narayan, Pradeep; Vaijapurkar, S G; Senwar, K R; Kumar, D; Bhatnagar, P K

    2008-01-01

    Commercial glasses have been investigated for their application in accidental gamma dose measurement using Thermoluminescent (TL) techniques. Some of the glasses have been found to be sensitive enough that they can be used as TL dating material in radiological accident situation for gamma dosimetry with lower detection limit 1 Gy (the dose significant for the onset of deterministic biological effects). The glasses behave linearly in the dose range 1-25 Gy with measurement uncertainty +/- 10%. The errors in accidental dose measurements using TL technique are estimated to be within +/- 25%. These glasses have shown TL fading in the range of 10-20% in 24 h after irradiation under room conditions; thereafter the fading becomes slower and reaches upto 50% in 15 d. TL fading of gamma-irradiated glasses follows exponential decay pattern, therefore dosimetry even after years is possible. These types of glasses can also be used as lethal dose indicator (3-4 Gy) using TL techniques, which can give valuable inputs to the medical professional for better management of radiation victims. The glasses are easy to use and do not require lengthy sample preparation before reading as in case of other building materials. TL measurement on glasses may give immediate estimation of the doses, which can help in medical triage of the radiation-exposed public. PMID:18285317

  14. Lethal and sub-lethal effects of faecal deltamethrin residues on dung-feeding insects.

    PubMed

    Mann, C M; Barnes, S; Offer, B; Wall, R

    2015-06-01

    Endectocides administered to livestock to facilitate pest and parasite control may be excreted in the faeces at concentrations that are toxic to coprophagous insects, including species of ecological importance. Although much research has focused on the effects of macrocyclic lactones, relatively less attention has been given to any similar impacts of the widely used pyrethroid insecticides. Here, the effects of faecal residues of the pyrethroid deltamethrin after application to Holstein-Friesian cattle in a proprietary pour-on formulation are examined. Freshly dropped dung was collected 1, 3, 5 and 7 days after treatment and from an untreated control group. In laboratory bioasssays, female Lucilia sericata (Diptera: Calliphoridae) blow flies matured significantly smaller egg batches and had a lower percentage of eggs hatch after feeding on dung collected for up to 5 days after treatment, compared with flies feeding on dung from untreated cattle. In the field, artificial dung pats were constructed from the collected dung and left on pastureland for 7 days before being retrieved and searched for insects. Significantly more adult Diptera emerged from the faeces of untreated cattle than from the dung of treated cattle collected on days 1 and 3 after treatment. Adult Coleoptera were found in lower numbers in the dung of treated animals compared with control dung, suggesting a repellent effect. The results indicate that deltamethrin residues in cattle faeces have a range of lethal and sub-lethal effects on dung-feeding insects for up to a week after treatment, but that the precise duration and nature of toxicity varies depending on the sensitivity of the insect in question. PMID:25594879

  15. Inhalation reference dose (RfDi): An application of interspecies dosimetry modeling for risk assessment of insoluble particles

    SciTech Connect

    Jarabek, A.M.; Menache, M.G.; Overton, H.; Dourson, M.L.; Miller, F.J.

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses (the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity) for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of the methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. The paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

  16. PCBS: CANCER DOSE-RESPONSE ASSESSMENT AND APPLICATION TO ENVIRONMENTAL MIXTURES (EXTERNAL REVIEW DRAFT)

    EPA Science Inventory

    A cancer dose-response assessment is developed for PCBS, considering toxicity, disposition, and environmental processes to evaluate human cancer risk. ow-dose linear models are applied to animal cancer studies of commercial mixtures to develop a range of potency estimates, then i...

  17. No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

    SciTech Connect

    Sheehan, Daniel M. . E-mail: dansheeh@swbell.net

    2006-01-15

    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 {approx}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.

  18. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  19. Dosimetric Comparison of 3-Dimensional Planning Techniques Using an Intravaginal Multichannel Balloon Applicator for High-Dose-Rate Gynecologic Brachytherapy

    SciTech Connect

    Park, Sang-June Chung, Melody; Demanes, D. Jeffrey; Banerjee, Robyn; Steinberg, Michael; Kamrava, Mitchell

    2013-11-15

    Purpose: To study the dosimetric differences of various channel combinations of the Capri vaginal applicator. Methods and Materials: The Capri consists of a single central channel (R1), an inner array of 6 channels (R2), and an outer array of 6 channels (R3). Three-dimensional plans were simulated for 6 channel arrangements (R1, R2, R12, R13, R23, and R123). Treatment plans were optimized to the applicator surface or 5-mm depth while minimizing dose to organs at risk (OARs: bladder, rectum, sigmoid, and urethra). The clinical target volume (CTV) was defined as a 5-mm circumferential shell extending 4 cm in length around the applicator. Clinical target volume coverage (D{sub mean}, D{sub 90}, V{sub 100}, and V{sub 150}) and OAR doses (D{sub 0.1} {sub cm{sup 3}}, D{sub 1} {sub cm{sup 3}}, D{sub 2} {sub cm{sup 3}}, and D{sub mean}) were compared. A comparison between the Capri (R123) and a conventional single-channel applicator was also done. Statistical significance (P value <.05) was evaluated with a 2-tailed t test. Results: When prescribing to 5-mm depth, CTV coverage using all 13 channels (R123) versus a single channel (R1) was similar; however, when prescribing to the surface there were differences (P<.0001) in all CTV metrics except for the V{sub 150}. The R1 plans had higher doses to all OARs compared with R123 plans (P<.007). Doses to OARs were not significantly different between R23 and R123 plans (P=.05-.95), and CTV coverage differences were on the order of 1%. Capri R123 plans provided slightly lower CTV D{sub 90} and D{sub mean} but equivalent OAR doses with smaller standard deviations compared with conventional cylinder plans for both prescriptions. Conclusions: The Capri multichannel applicator provides equivalent target coverage at 5-mm depth, with significantly reduced dose to OARs relative to using a single channel. Optimal plans can be achieved using R12 (lowest V{sub 150}) or R123 or R23 (lowest OAR doses)

  20. Sub-lethal glyphosate exposure alters flowering phenology and causes transient male-sterility in Brassica spp

    PubMed Central

    2014-01-01

    Background Herbicide resistance in weedy plant populations can develop through different mechanisms such as gene flow of herbicide resistance transgenes from crop species into compatible weedy species or by natural evolution of herbicide resistance or tolerance following selection pressure. Results from our previous studies suggest that sub-lethal levels of the herbicide glyphosate can alter the pattern of gene flow between glyphosate resistant Canola®, Brassica napus, and glyphosate sensitive varieties of B. napus and B. rapa. The objectives of this study were to examine the phenological and developmental changes that occur in Brassica crop and weed species following sub-lethal doses of the herbicides glyphosate and glufosinate. We examined several vegetative and reproductive traits of potted plants under greenhouse conditions, treated with sub-lethal herbicide sprays. Results Our results indicate that exposure of Brassica spp. to a sub-lethal dose of glyphosate results in altering flowering phenology and reproductive function. Flowering of all sensitive species was significantly delayed and reproductive function, specifically male fertility, was suppressed. Higher dosage levels typically contributed to an increase in the magnitude of phenotypic changes. Conclusions These results demonstrate that Brassica spp. plants that are exposed to sub-lethal doses of glyphosate could be subject to very different pollination patterns and an altered pattern of gene flow that would result from changes in the overlap of flowering phenology between species. Implications include the potential for increased glyphosate resistance evolution and spread in weedy communities exposed to sub-lethal glyphosate. PMID:24655547

  1. Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

    SciTech Connect

    Li Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Toncheva, Greta; Yoshizumi, Terry T.; Frush, Donald P.

    2011-01-15

    Purpose: Current methods for estimating and reporting radiation dose from CT examinations are largely patient-generic; the body size and hence dose variation from patient to patient is not reflected. Furthermore, the current protocol designs rely on dose as a surrogate for the risk of cancer incidence, neglecting the strong dependence of risk on age and gender. The purpose of this study was to develop a method for estimating patient-specific radiation dose and cancer risk from CT examinations. Methods: The study included two patients (a 5-week-old female patient and a 12-year-old male patient), who underwent 64-slice CT examinations (LightSpeed VCT, GE Healthcare) of the chest, abdomen, and pelvis at our institution in 2006. For each patient, a nonuniform rational B-spine (NURBS) based full-body computer model was created based on the patient's clinical CT data. Large organs and structures inside the image volume were individually segmented and modeled. Other organs were created by transforming an existing adult male or female full-body computer model (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. A Monte Carlo program previously developed and validated for dose simulation on the LightSpeed VCT scanner was used to estimate patient-specific organ dose, from which effective dose and risks of cancer incidence were derived. Patient-specific organ dose and effective dose were compared with patient-generic CT dose quantities in current clinical use: the volume-weighted CT dose index (CTDI{sub vol}) and the effective dose derived from the dose-length product (DLP). Results: The effective dose for the CT examination of the newborn patient (5.7 mSv) was higher but comparable to that for the CT examination of the teenager patient (4.9 mSv) due to the size-based clinical CT protocols at our institution, which employ lower scan techniques for smaller

  2. CD4+ T cells provide protection against acute lethal encephalitis caused by Venezuelan equine encephalitis virus

    PubMed Central

    Yun, Nadezhda E.; Peng, Bi-Hung; Bertke, Andrea S.; Borisevich, Viktoriya; Smith, Jennifer K.; Smith, Jeanon N.; Poussard, Allison L.; Salazar, Milagros; Judy, Barbara M.; Zacks, Michele A.; Estes, D. Mark; Paessler, Slobodan

    2009-01-01

    Studying the mechanisms of host survival resulting from viral encephalitis is critical to the development of vaccines. Here we have shown in several independent studies that high-dose treatment with neutralizing antibody prior to intranasal infection with Venezuelan equine encephalitis virus had an antiviral effect in the visceral organs and prolonged survival time of infected mice, even in the absence of alpha beta T cells. Nevertheless, the antibody treatment did not prevent the development of lethal encephalitis. In contrary, the adoptive transfer of primed CD4+ T cells is necessary to prevent lethal encephalitis in mice lacking alpha beta T cell receptor. PMID:19446933

  3. Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma

    PubMed Central

    Werthmann, Paul Georg; Helling, Dieter; Heusser, Peter; Kienle, Gunver Sophia

    2014-01-01

    Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically originates in the salivary glands. Surgical removal can lead to functional loss and psychological distress. Viscum album extract (VAE) is a herbal remedy with dose-dependent cytotoxic, apoptogenic and immunological effects. In some case reports, tumour regression has been observed following high-dose local applications of VAE. An active 88-year-old man with fast-growing ACC of the hard palate refused surgical removal and received high-dose intratumoural injections of VAE (alone) over a 10-month period. The tumour decreased in size, softened and loosened from its surroundings. A biopsy during the course showed inflammation. The patient remained well and without functional limitations during the therapy and follow-up period (5 months). VAE produced no reported side effects. This aged patient exemplifies a satisfying course of ACC under VAE resulting in good quality of life and partial tumour regression. PMID:25082867

  4. Application of a Pelletron accelerator to study total dose radiation effects on 50 GHz SiGe HBTs

    NASA Astrophysics Data System (ADS)

    Praveen, K. C.; Pushpa, N.; Naik, P. S.; Cressler, John D.; Tripathi, Ambuj; Gnana Prakash, A. P.

    2012-02-01

    We have investigated the effects of 50 MeV lithium ion irradiation on the DC electrical characteristics of first-generation silicon-germanium heterojunction bipolar transistors (50 GHz SiGe HBTs) in the dose range of 600 krad to 100 Mrad. The results of 50 MeV Li 3+ ion irradiation on the SiGe HBTs are compared with 63 MeV proton and Co-60 gamma irradiation results in the same dose range in order to understand the damage induced by different LET species. The radiation response of emitter-base (EB) spacer oxide and shallow trench isolation (STI) oxide to different irradiation types are discussed in this paper. We have also focused on the efficacy in the application of a Pelletron accelerator to study total dose irradiation studies in SiGe HBTs.

  5. Fast dose kernel interpolation using Fourier transform with application to permanent prostate brachytherapy dosimetry

    SciTech Connect

    Liu, Derek Sloboda, Ron S.

    2014-05-15

    Purpose: Boyer and Mok proposed a fast calculation method employing the Fourier transform (FT), for which calculation time is independent of the number of seeds but seed placement is restricted to calculation grid points. Here an interpolation method is described enabling unrestricted seed placement while preserving the computational efficiency of the original method. Methods: The Iodine-125 seed dose kernel was sampled and selected values were modified to optimize interpolation accuracy for clinically relevant doses. For each seed, the kernel was shifted to the nearest grid point via convolution with a unit impulse, implemented in the Fourier domain. The remaining fractional shift was performed using a piecewise third-order Lagrange filter. Results: Implementation of the interpolation method greatly improved FT-based dose calculation accuracy. The dose distribution was accurate to within 2% beyond 3 mm from each seed. Isodose contours were indistinguishable from explicit TG-43 calculation. Dose-volume metric errors were negligible. Computation time for the FT interpolation method was essentially the same as Boyer's method. Conclusions: A FT interpolation method for permanent prostate brachytherapy TG-43 dose calculation was developed which expands upon Boyer's original method and enables unrestricted seed placement. The proposed method substantially improves the clinically relevant dose accuracy with negligible additional computation cost, preserving the efficiency of the original method.

  6. New form of platyspondylic lethal chondrodysplasia.

    PubMed

    Akaba, K; Nishimura, G; Hashimoto, M; Wakabayashi, T; Kanasugi, H; Hayasaka, K

    1996-12-30

    We report on a sporadic case of hitherto unknown lethal skeletal dysplasia. The cardinal clinical manifestations consisted of frontal bossing, cloudy corneae, low nasal ridge, and micrognathia, hypoplastic thorax, and rhizomelic micromelia. Laryngoscopy and neck CT disclosed laryngeal stenosis, and brain CT demonstrated hypoplasia of the corpus callosum. Skeletal survey demonstrated hypoplasia of facial bones and short skull base, extremely severe platyspondyly, hypoplastic ilia, and delayed epiphyseal ossification and rhizomelic shortness of tubular bones. The long bones appeared overtubulated with exaggerated metaphyseal flaring. The humeri were particularly short and bowed. Bowing of the radii and ulnae with subluxation of radial heads presented as a Madelung-like deformity. Unlike the long bones, the short tubular bones were not short and normally modeled. The skeletal changes were superficially similar to those in a group of lethal platyspondylic chondrodysplasias, but were inconsistent with any known subtypes of this group or other lethal skeletal dysplasias. PMID:8989469

  7. Lethal Injection for Execution: Chemical Asphyxiation?

    PubMed Central

    Zimmers, Teresa A; Sheldon, Jonathan; Lubarsky, David A; López-Muñoz, Francisco; Waterman, Linda; Weisman, Richard; Koniaris, Leonidas G

    2007-01-01

    Background Lethal injection for execution was conceived as a comparatively humane alternative to electrocution or cyanide gas. The current protocols are based on one improvised by a medical examiner and an anesthesiologist in Oklahoma and are practiced on an ad hoc basis at the discretion of prison personnel. Each drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, was expected to be lethal alone, while the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. We sought to determine whether the current drug regimen results in death in the manner intended. Methods and Findings We analyzed data from two US states that release information on executions, North Carolina and California, as well as the published clinical, laboratory, and veterinary animal experience. Execution outcomes from North Carolina and California together with interspecies dosage scaling of thiopental effects suggest that in the current practice of lethal injection, thiopental might not be fatal and might be insufficient to induce surgical anesthesia for the duration of the execution. Furthermore, evidence from North Carolina, California, and Virginia indicates that potassium chloride in lethal injection does not reliably induce cardiac arrest. Conclusions We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable. PMID:17455994

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

    NASA Astrophysics Data System (ADS)

    Kalita, J. M.; Wary, G.

    2016-09-01

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

  9. Long-term sub-lethal effects of low concentration commercial herbicide (glyphosate/pelargonic acid) formulation in Bryophyllum pinnatum.

    PubMed

    Pokhrel, Lok R; Karsai, Istvan

    2015-12-15

    Potential long-term (~7months) sub-lethal impacts of soil-applied low levels of Roundup herbicide formulation were investigated in a greenhouse environment using the vegetative clones of succulent non-crop plant model, Bryophyllum pinnatum (Lam.) Oken. An eleven day LC50 (concentration that killed 50% of the plants) was found to be 6.25% (~1.25mg glyphosate/mL and 1.25mg pelargonic acid/mL combined), and complete mortality occurred at 12.5%, of the field application rate (i.e., ~20mg glyphosate/mL and 20mg pelargonic acid/mL as active ingredients). While sub-lethal Roundup (1-5%) exposures led to hormesis-characterized by a significant increase in biomass and vegetative reproduction, higher concentrations (≥6.25%) were toxic. A significant interaction between Roundup concentrations and leaf biomass was found to influence the F1 plantlets' biomass. Biomass asymmetry generally increased with increasing Roundup concentrations, indicating that plants were more stressed at higher Roundup treatments but within the low-dose regime (≤5% of the as-supplied formulation). While leaf apex region demonstrated higher reproduction with lower biomass increase, leaf basal area showed lower reproduction with greater biomass increase, in plantlets. The results suggest long-term exposures to drifted low levels of Roundup in soil may promote biomass and reproduction in B. pinnatum. PMID:26311583

  10. Application of Antibiotic Pharmacodynamics and Dosing Principles in Patients With Sepsis.

    PubMed

    Droege, Molly E; Van Fleet, Suzanne L; Mueller, Eric W

    2016-04-01

    Sepsis is associated with marked mortality, which may be reduced by prompt initiation of adequate, appropriate doses of antibiotic. Critically ill patients often have physiological changes that reduce blood and tissue concentrations of antibiotic and high rates of multidrug-resistant pathogens, which may affect patients' outcomes. All critical care professionals, including critical care nurses, should understand antibiotic pharmacokinetics and pharmacodynamics to ensure sound antibiotic dosing and administration strategies for optimal microbial killing and patients' outcomes. Effective pathogen eradication occurs when the dose of antibiotic reaches or maintains optimal concentrations relative to the minimum inhibitory concentration for the pathogen. Time-dependent antibiotics, such as β-lactams, can be given as extended or continuous infusions. Concentration-dependent antibiotics such as aminoglycosides are optimized by using high, once-daily dosing strategies with serum concentration monitoring. Vancomycin and fluoroquinolones are dependent on both time and concentration above the minimum inhibitory concentration. PMID:27037336

  11. Dosimetry in steep dose-rate gradient radiation fields: A challenge in clinical applications

    SciTech Connect

    Massillon-JL, G.

    2010-12-07

    The fundamental goal of radiotherapy is to reduce the damage to normal tissue and optimize the dose to the tumor with an associated high probability of cure. Because of this, an accurate and precise knowledge of the radiation dose distribution delivered around the tumor volume during radiotherapy treatments such as stereotactic radiosurgery, intensity modulated radiotherapy or brachytherapy with low-energy X-ray and beta particle sources is of great importance. However, in each of these radiation fields, there exists a steep dose-rate gradient which makes it very difficult to perform accurate dose measurements. In this work, the physics phenomena involved in the energy absorption for each of these situations are discussed, and a brief revision of what the Medical Physics community is doing is presented.

  12. Dosimetry in steep dose-rate gradient radiation fields: A challenge in clinical applications

    NASA Astrophysics Data System (ADS)

    Massillon-JL, G.

    2010-12-01

    The fundamental goal of radiotherapy is to reduce the damage to normal tissue and optimize the dose to the tumor with an associated high probability of cure. Because of this, an accurate and precise knowledge of the radiation dose distribution delivered around the tumor volume during radiotherapy treatments such as stereotactic radiosurgery, intensity modulated radiotherapy or brachytherapy with low-energy X-ray and beta particle sources is of great importance. However, in each of these radiation fields, there exists a steep dose-rate gradient which makes it very difficult to perform accurate dose measurements. In this work, the physics phenomena involved in the energy absorption for each of these situations are discussed, and a brief revision of what the Medical Physics community is doing is presented.

  13. MODEL DEVELOPMENT AND APPLICATION FOR ASSESSING HUMAN EXPOSURE AND DOSE TO TOXIC CHEMICALS AND POLLUTANTS

    EPA Science Inventory

    This project aims to strengthen the general scientific foundation of EPA's exposure and risk assessment processes by developing state-of-the-art exposure to dose computational models. This research will produce physiologically-based pharmacokinetic (PBPK) and pharmacodynamic (PD)...

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

    EPA Science Inventory

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

  15. Study on GEANT4 code applications to dose calculation using imaging data

    NASA Astrophysics Data System (ADS)

    Lee, Jeong Ok; Kang, Jeong Ku; Kim, Jhin Kee; Kwon, Hyeong Cheol; Kim, Jung Soo; Kim, Bu Gil; Jeong, Dong Hyeok

    2015-07-01

    The use of the GEANT4 code has increased in the medical field. Various studies have calculated the patient dose distributions by users the GEANT4 code with imaging data. In present study, Monte Carlo simulations based on DICOM data were performed to calculate the dose absorb in the patient's body. Various visualization tools are installed in the GEANT4 code to display the detector construction; however, the display of DICOM images is limited. In addition, to displaying the dose distributions on the imaging data of the patient is difficult. Recently, the gMocren code, a volume visualization tool for GEANT4 simulation, was developed and has been used in volume visualization of image files. In this study, the imaging based on the dose distributions absorbed in the patients was performed by using the gMocren code. Dosimetric evaluations with were carried out by using thermo luminescent dosimeter and film dosimetry to verify the calculated results.

  16. APPLICATION OF BENCHMARK DOSE METHODOLOGY TO DATA FROM PRENATAL DEVELOPMENTAL TOXICITY STUDIES

    EPA Science Inventory

    The benchmark dose (BMD) concept was applied to 246 conventional developmental toxicity datasets from government, industry and commercial laboratories. Five modeling approaches were used, two generic and three specific to developmental toxicity (DT models). BMDs for both quantal ...

  17. ESTIMATING CONTAMINANT DOSE FOR INTERMITTENT DERMAL CONTACT: MODEL DEVELOPMENT, TESTING, AND APPLICATION

    EPA Science Inventory

    Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure sc...

  18. Live deaths online: internet suicide and lethality.

    PubMed

    Klein, Carolina A

    2012-01-01

    The Internet provides an infinite platform for the portrayal of lethal events. Beyond mere display, however, it dispenses information, allows for participation and sharing of content, and constitutes a virtual interactive forum. The Internet may ultimately shape society's approach to perceiving and dealing with death. Thus, psychiatrists may wish to be aware of these matters so that they may be considered in assessments and clinical care. In this article, the author attempts to identify key online locations where lethality is portrayed and how it may affect the individual patient and practitioner and the population at large. PMID:23233475

  19. Applicability of dose conversion coefficients of ICRP 74 to Asian adult males: Monte Carlo simulation study.

    PubMed

    Lee, Choonsik; Lee, Choonik; Lee, Jai-Ki

    2007-05-01

    International Commission on Radiological Protection (ICRP) reported comprehensive dose conversion coefficients for adult population, which is exposed to external photon sources in the Publication 74. However, those quantities were calculated from so-called stylized (or mathematical) phantoms composed of simplified mathematical surface equations so that the discrepancy between the phantoms and real human anatomy has been investigated by several authors using Caucasian-based voxel phantoms. To address anatomical and racial limitations of the stylized phantoms, several Asian-based voxel phantoms have been developed by Korean and Japanese investigators, independently. In the current study, photon dose conversion coefficients of ICRP 74 were compared with those from a total of five Asian-based male voxel phantoms, whose body dimensions were almost identical. Those of representative radio-sensitive organs (testes, red bone marrow, colon, lungs, and stomach), and effective dose conversion coefficients were obtained for comparison. Even though organ doses for testes, colon and lungs, and effective doses from ICRP 74 agreed well with those from Asian voxel phantoms within 10%, absorbed doses for red bone marrow and stomach showed significant discrepancies up to 30% which was mainly attributed to difference of phantom description between stylized and voxel phantoms. This study showed that the ICRP 74 dosimetry data, which have been reported to be unrealistic compared to those from Caucasian-based voxel phantoms, are also not appropriate for Asian population. PMID:17337194

  20. External dose estimates for Dolon village: application of the U.S./Russian joint methodology.

    PubMed

    Simon, Steven L; Beck, Harold L; Gordeev, Konstantin; Bouville, André; Anspaugh, Lynn R; Land, Charles E; Luckyanov, Nicholas; Shinkarev, Sergey

    2006-02-01

    Methods to estimate external dose from radioactive fallout from nuclear tests have for many years depended on two types of data: measurements of exposure rate in air and an empirically derived power function to describe the change in exposure rate with time, Over the last four years, a working group with American and Russian participation has developed a bi-national joint methodology that offers an improved capability for estimating external dose. In this method, external dose is estimated using exposure rate functions derived from data from American nuclear tests similar in construction to SNTS (Semipalatinsk Nuclear Test Site) devices. For example, in this paper, we derive doses for test #1 (August 29, 1949) at the SNTS using an exposure rate function for the U.S. TRINITY test. For the case of test #1, the average external dose for a person in Dolon is estimated to have been about 0.5 Gy compared to 1 to 2 Gy estimated in other work. This prediction agrees better with reported EPR measurements in teeth from village residents and with measurements of TL signals in bricks from Dolon buildings. This report presents the basic elements of the joint methodology model for estimation of external dose received from SNTS fallout. PMID:16571929

  1. Characterization of a new photo-fluorescent film dosimeter for high-radiation dose applications

    SciTech Connect

    Murphy, Mark K. ); Miller, Steven D. ); Kovacs, Andras; Mclaughlin, William L.; Slezsak, Istvan

    2001-12-01

    Characterization studies on one of the first versions of the Sunna fluorescent dosimeter have been published by Kovacs and McLaughlin. This present study describes testing results of a newer version of the dosimeter (Model and 61543;, batch 0399-20). This dosimeter is a 1-cm by 3-cm polymeric film of 0.5 mm thickness that emits a green fluorescence component at intensities almost linear with dose. The manufacturing method (injection molding) allows potential batch sizes on the order of a million while maintaining a signal precision on the order of+/- 1%. Studies include dose response, dose rate dependence, energy dependence, post-irradiation stability, environmental effects, and variation of response within a batch. Data for both food irradiation and sterilization dose levels were obtained. The results indicate that the green signal (0.3-200 kGy) works well for food irradiation dose levels, especially in refrigerated facilities that maintain tight temperature control. The green signal also works well in sterilization facilities because its irradiation temperature coefficient above room temperature is minimal at sterilization doses. If the user requires readout results in less than 22 hours after room temperature irradiation, the user can either calibrate for a specific post-irradiation readout time(s) or simply heat the dosimeters in a small laboratory oven to quickly stabilize the signal.

  2. Developing a virtual reality application for training nuclear power plant operators: setting up a database containing dose rates in the refuelling plant.

    PubMed

    Ródenas, J; Zarza, I; Burgos, M C; Felipe, A; Sánchez-Mayoral, M L

    2004-01-01

    Operators in Nuclear Power Plants can receive high doses during refuelling operations. A training programme for simulating refuelling operations will be useful in reducing the doses received by workers as well as minimising operation time. With this goal in mind, a virtual reality application is developed within the framework of the CIPRES project. The application requires doses, both instantaneous and accumulated, to be displayed at all times during operator training. Therefore, it is necessary to set up a database containing dose rates at every point in the refuelling plant. This database is based on radiological protection surveillance data measured in the plant during refuelling operations. Some interpolation routines have been used to estimate doses through the refuelling plant. Different assumptions have been adopted in order to perform the interpolation and obtain consistent data. In this paper, the procedures developed to set up the dose database for the virtual reality application are presented and analysed. PMID:15266073

  3. Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs

    PubMed Central

    Turner, Wendy C.; Kausrud, Kyrre L.; Beyer, Wolfgang; Easterday, W. Ryan; Barandongo, Zoë R.; Blaschke, Elisabeth; Cloete, Claudine C.; Lazak, Judith; Van Ert, Matthew N.; Ganz, Holly H.; Turnbull, Peter C. B.; Stenseth, Nils Chr.; Getz, Wayne M.

    2016-01-01

    To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1–2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways. PMID:27265371

  4. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge

    PubMed Central

    Savers, Amélie; Rasid, Orhan; Parlato, Marianna; Brock, Matthias; Jouvion, Gregory; Ryffel, Bernhard; Cavaillon, Jean-Marc; Eberl, Gerard; Ibrahim-Granet, Oumaïma

    2016-01-01

    Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection. PMID:27078879

  5. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge.

    PubMed

    Savers, Amélie; Rasid, Orhan; Parlato, Marianna; Brock, Matthias; Jouvion, Gregory; Ryffel, Bernhard; Cavaillon, Jean-Marc; Eberl, Gerard; Ibrahim-Granet, Oumaïma

    2016-01-01

    Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection. PMID:27078879

  6. Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs.

    PubMed

    Turner, Wendy C; Kausrud, Kyrre L; Beyer, Wolfgang; Easterday, W Ryan; Barandongo, Zoë R; Blaschke, Elisabeth; Cloete, Claudine C; Lazak, Judith; Van Ert, Matthew N; Ganz, Holly H; Turnbull, Peter C B; Stenseth, Nils Chr; Getz, Wayne M

    2016-01-01

    To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1-2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways. PMID:27265371

  7. APPLICATION OF THE EXPOSURE DOSE ESTIMATING MODEL (ERDEM) TO ASSESSMENT OF DERMAL EXPOSURE IN THE RAT TO MALATHION

    EPA Science Inventory

    APPLICATION OF THE EXPOSURE DOSE ESTIMATING MODEL (ERDEM) TO ASSESSMENT OF DERMAL EXPOSURE IN THE RAT TO MALATHION.
    Evans, M.V1., Power, F.W2., Dary, C.C2., Tornero-Velez, R2., and Blancato, J.N2.
    1 NHEERL, US EPA, ORD, ETD, RTP, NC; 2 NERL, US EPA, ORD, EDRB, LV, NV
    Re...

  8. Lethal and sub-lethal effects on the Asian common toad Duttaphrynus melanostictus from exposure to hexavalent chromium.

    PubMed

    Fernando, Vindhya A K; Weerasena, Jagathpriya; Lakraj, G Pemantha; Perera, Inoka C; Dangalle, Chandima D; Handunnetti, Shiroma; Premawansa, Sunil; Wijesinghe, Mayuri R

    2016-08-01

    Chromium discharged in industrial effluents frequently occurs as an environmental pollutant, but the lethal and sub-lethal effects the heavy metal might cause in animals exposed to it have been insufficiently investigated. Selecting the amphibian Duttaphrynus melanostictus, we carried out laboratory tests to investigate the effects of short and long term exposure to hexavalent chromium (Cr(VI)) in both tadpoles and adult toads. The concentrations used were 0.002, 0.02, 0.2, 1.0 and 2.0mg/L, the first three corresponding to field levels. In vitro exposures were also carried out using toad erythrocytes and Cr(VI) concentrations of 0.0015, 0.003, 0.015, 0.03, 0.15mg/L. Mortality, growth retardation, developmental delays and structural aberrations were noted in the metal-treated tadpoles, with increasing incidence corresponding to increase in Cr(VI) level and duration of exposure. Many of the sub-lethal effects were evident with long term exposure to environmentally relevant levels of the toxicant. Changes in selected blood parameters and erythrocyte morphometry were also detected in Cr(VI) exposed toads, indicating anaemic and leucopenic conditions. In the genotoxicity study, DNA damage indicated by comet assay and increased micronuclei frequency, occurred at the low Cr(VI) concentrations tested. The multiple deleterious effects of exposure to chromium signal the need for monitoring and controlling the discharge of chromium to the environment. The dose-dependency and genotoxic effects observed in this widely distributed Asian toad indicates its suitability for monitoring heavy metal pollution in aquatic systems. PMID:27262939

  9. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

    PubMed

    Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. PMID:24971906

  10. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    SciTech Connect

    Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti

  11. Lethal Malaria: Marchiafava and Bignami Were Right

    PubMed Central

    White, Nicholas J.; Turner, Gareth D. H.; Day, Nicholas P. J.; Dondorp, Arjen M.

    2013-01-01

    One hundred and twenty years ago, the Italian malariologists Marchiafava and Bignami proposed that the fundamental pathological process underlying lethal falciparum malaria was microvascular obstruction. Since then, several alternative hypotheses have been proposed. These formed the basis for adjunctive interventions, which have either been ineffective or harmful. Recent evidence strongly suggests that Marchiafava and Bignami were right. PMID:23585685

  12. The evolution of lethal intergroup violence

    PubMed Central

    Kelly, Raymond C.

    2005-01-01

    Recent findings and analyses in evolutionary biology, archaeology, and ethnology provide a favorable conjuncture for examining the evolution of lethal intergroup violence among hominids during the 2.9-million-year Paleolithic time span. Here, I seek to identify and investigate the main turning points in this evolutionary trajectory and to delineate the periodization that follows from this inquiry. PMID:16129826

  13. Deadly Lessons: Understanding Lethal School Violence.

    ERIC Educational Resources Information Center

    Moore, Mark H., Ed.; Petrie, Carol V., Ed.; Braga, Anthony A., Ed.; McLaughlin, Brenda L., Ed.

    This collection of papers is the outcome of the National Academies' effort to glean information from six different case studies of student-perpetrated school shootings. Part 1, "Case Studies of Lethal School Violence," includes: "The Copycat Factor: Mental Illness, Guns, and the Shooting Incident at Heritage High School, Rockdale County, Georgia"…

  14. Clinical application of Chamomilla recutita in phlebitis: dose response curve study.

    PubMed

    Reis, Paula Elaine Diniz Dos; Carvalho, Emilia Campos de; Bueno, Paula Carolina Pires; Bastos, Jairo Kenupp

    2011-01-01

    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. PMID:21412623

  15. Application of the inverse Monte Carlo treatment planning system IKO for an inhomogeneous dose prescription in the sense of dose painting.

    PubMed

    Rickhey, Mark; Bogner, Ludwig

    2006-01-01

    Biological imaging (PET SPECTJfMRI, MRS, etc.) is able to provide tri-dimensional biological information, i.e. proliferation, cell density, hypoxia or choline/citrate ratio. The implementation of this information in a treatment plan can be utilised to escalate the dose in target subvolumes. For this purpose, a treatment planning system has to be able to realise an inhomogeneous dose prescription with sufficient spatial resolution. The present study investigated to which extent the inverse Monte Carlo treatment planning system IKO (inverse kernel optimization), developed at our department, can modulate an inhomogeneous dose prescription. As a qualifier to describe this ability, we defined in analogy to imaging a modulation transfer function for treatment planning systems. In addition two clinical cases, a prostate case and a head-and-neck case, were set up with different dose prescriptions in different subtargets. The modulation transfer function revealed that IKO is able to modulate structures larger than 1.3 cm with sharp dose gradients. Also, IKO is able to modulate several subtargets inside a prostate with different escalated doses. The dose-volume histograms of the head-and-neck case showed a good dose coverage of the target volumes, as well as a good protection of the organs at risk according to the dose constraints. As a result, IKO is able to realise a heterogeneous dose prescription in the sense of "dose painting". PMID:17216756

  16. Interspecies Allometric Scaling of Antimalarial Drugs and Potential Application to Pediatric Dosing

    PubMed Central

    Senarathna, S. M. D. K. Ganga

    2014-01-01

    Pharmacopeial recommendations for administration of antimalarial drugs are the same weight-based (mg/kg of body weight) doses for children and adults. However, linear calculations are known to underestimate pediatric doses; therefore, interspecies allometric scaling data may have a role in predicting doses in children. We investigated the allometric scaling relationships of antimalarial drugs using data from pharmacokinetic studies in mammalian species. Simple allometry (Y = a × Wb) was utilized and compared to maximum life span potential (MLP) correction. All drugs showed a strong correlation with clearance (CL) in healthy controls. Insufficient data from malaria-infected species other than humans were available for allometric scaling. The allometric exponents (b) for CL of artesunate, dihydroartemisinin (from intravenous artesunate), artemether, artemisinin, clindamycin, piperaquine, mefloquine, and quinine were 0.71, 0.85, 0.66, 0.83, 0.62, 0.96, 0.52, and 0.40, respectively. Clearance was significantly lower in malaria infection than in healthy (adult) humans for quinine (0.07 versus 0.17 liter/h/kg; P = 0.0002) and dihydroartemisinin (0.81 versus 1.11 liters/h/kg; P = 0.04; power = 0.6). Interpolation of simple allometry provided better estimates of CL for children than MLP correction, which generally underestimated CL values. Pediatric dose calculations based on simple allometric exponents were 10 to 70% higher than pharmacopeial (mg/kg) recommendations. Interpolation of interspecies allometric scaling could provide better estimates than linear scaling of adult to pediatric doses of antimalarial drugs; however, the use of a fixed exponent for CL was not supported in the present study. The variability in allometric exponents for antimalarial drugs also has implications for scaling of fixed-dose combinations. PMID:25092696

  17. Cholesterol Metabolism and Prostate Cancer Lethality.

    PubMed

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR. PMID:27325648

  18. A model of CT dose profiles in Banach space; with applications to CT dosimetry.

    PubMed

    Weir, Victor J

    2016-07-01

    In this paper the scatter component of computed tomography dose profiles is modeled using the solution to a nonlinear ordinary differential equation. This scatter function is summed with a modeled primary function of approximate trapezoidal shape. The primary dose profile is modeled to include the analytic continuation of the Heaviside step function. A mathematical theory is developed in a Banach space. The modeled function is used to accurately fit data from a 256-slice GE Revolution scanner. A 60 cm long body phantom is assembled and used for data collection with both a pencil chamber and a Farmer-type chamber. PMID:27300276

  19. A model of CT dose profiles in Banach space; with applications to CT dosimetry

    NASA Astrophysics Data System (ADS)

    Weir, Victor J.

    2016-07-01

    In this paper the scatter component of computed tomography dose profiles is modeled using the solution to a nonlinear ordinary differential equation. This scatter function is summed with a modeled primary function of approximate trapezoidal shape. The primary dose profile is modeled to include the analytic continuation of the Heaviside step function. A mathematical theory is developed in a Banach space. The modeled function is used to accurately fit data from a 256-slice GE Revolution scanner. A 60 cm long body phantom is assembled and used for data collection with both a pencil chamber and a Farmer-type chamber.

  20. Novel application of high-dose rate brachytherapy for severe, recalcitrant palmoplantar pustulosis.

    PubMed

    Timerman, D; Devlin, P M; Nambudiri, V E; Wright, N A; Vleugels, R A; Clark, R A; Kupper, T S; Merola, J F; Patel, M

    2016-07-01

    Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain, often limiting daily activities. We present the case of a 36-year-old man with severe PPP who had treatment failure with multiple medical therapies but showed marked improvement with high-dose rate brachytherapy. Brachytherapy has the advantage of providing a conformal dose distribution over complex curved surfaces, such as the foot and ankle. Our observations suggest that brachytherapy may be a well-tolerated treatment option for patients with severe, refractory PPP. PMID:26848819

  1. 4D SPECT/CT acquisition for 3D dose calculation and dose planning in (177)Lu-peptide receptor radionuclide therapy: applications for clinical routine.

    PubMed

    Kairemo, Kalevi; Kangasmäki, Aki

    2013-01-01

    Molecular radiotherapy combines the potential of a specific tracer (vector) targeting tumor cells with local radiotoxicity. Designing a specific tumor-targeting/killing combination is a tailoring process. Radionuclides with imaging capacity serve best in the selection of the targeting molecule. The potential of targeted therapy with radiolabeled peptides has been reported in many conditions; peptide receptor radionuclide therapy (PRRT) is already part of Scandinavian guidelines for treating neuroendocrine tumors. Lu-177- and Y-90-labeled somatostatin analogs, including DOTATOC, DOTANOC, and DOTATATE, are most the commonly used and have turned out to be effective. For routine use, an efficient, rapid, and reliable dose calculation tool is needed. In this chapter we describe how serial pre- and posttherapeutic scans can be used for dose calculation and for predicting therapy doses. Our software for radionuclide dose calculation is a three-dimensional, voxel-based system. The 3D dose calculation requires coregistered SPECT image sets from several time points after infusion to reconstruct time-activity curves for each voxel. Image registration is done directly by SPECT image registration using the first time point as a target. From the time-activity curves, initial activity and total half-life maps are calculated to produce a cumulated activity map. The cumulated activity map is then convoluted with a voxel-dose kernel to obtain a 3D dose map. We performed dose calculations similarly for both therapeutic and preplanning images. Preplanning dose was extrapolated to predict therapy dose using the ratio of administered activities. Our 3D dose calculation results are also compared with those of OLINDA. Our preliminary results indicate that dose planning using pretherapeutic scanning can predict critical organ and tumor doses. In some cases, the dose planning prediction resulted in slight, and slightly dose-dependent, overestimation of final therapy dose. Real tumor dose

  2. Optimal unified combination rule in application of Dempster-Shafer theory to lung cancer radiotherapy dose response outcome analysis.

    PubMed

    He, Yanyan; Hussaini, M Yousuff; Gong, Yutao U T; Xiao, Ying

    2016-01-01

     Our previous study demonstrated the application of the Dempster-Shafer theory of evidence to dose/volume/outcome data analysis. Specifically, it provided Yager's rule to fuse data from different institutions pertaining to radiotherapy pneumonitis versus mean lung dose. The present work is a follow-on study that employs the optimal unified combination rule, which optimizes data similarity among inde-pendent sources. Specifically, we construct belief and plausibility functions on the lung cancer radiotherapy dose outcome datasets, and then apply the optimal uni-fied combination rule to obtain combined belief and plausibility, which bound the probabilities of pneumonitis incidence. To estimate the incidence of pneumonitis at any value of mean lung dose, we use the Lyman-Kutcher-Burman (LKB) model to fit the combined belief and plausibility curves. The results show that the optimal unified combination rule yields a narrower uncertainty range (as represented by the belief-plausibility range) than Yager's rule, which is also theoretically proven. PMID:26894343

  3. Linear relationship between lethal mutation yield and intake of ethyl methanesulfonate in Drosophila melanogaster

    SciTech Connect

    Ayaki, T.; Oshima, K.; Yoshikawa, I.

    1985-01-01

    Males of Drosophila melanogaster were fed sucrose solutions containing various concentrations of EMS (from 0.25 to 10mM) for 24 hr. To measure the intake of an EMS solution, /sup 3/H-labeled sucrose was added to the feeding solution, and the /sup 3/H activity inside the flies was used as a measure for the intake volume of EMS solution. The relationship between the estimated absorbed dose and the exposure concentration was almost linear in a low concentration range but became concave with a downward curvature in a high concentration range. The dose-response relationship between the frequency of sex-linked recessive lethals and the estimated absorbed dose showed no deviation from linearity at all the five absorbed doses tested. It may be concluded that the absorbed doses thus estimated were very close to true absorbed doses, indicating the usefulness of the present method for dosimetry of chemicals to be given to files.

  4. Monte Carlo-based dose calculation for 32P patch source for superficial brachytherapy applications

    PubMed Central

    Sahoo, Sridhar; Palani, Selvam T.; Saxena, S. K.; Babu, D. A. R.; Dash, A.

    2015-01-01

    Skin cancer treatment involving 32P source is an easy, less expensive method of treatment limited to small and superficial lesions of approximately 1 mm deep. Bhabha Atomic Research Centre (BARC) has indigenously developed 32P nafion-based patch source (1 cm × 1 cm) for treating skin cancer. For this source, the values of dose per unit activity at different depths including dose profiles in water are calculated using the EGSnrc-based Monte Carlo code system. For an initial activity of 1 Bq distributed in 1 cm2 surface area of the source, the calculated central axis depth dose values are 3.62 × 10-10 GyBq-1 and 8.41 × 10-11 GyBq-1at 0.0125 and 1 mm depths in water, respectively. Hence, the treatment time calculated for delivering therapeutic dose of 30 Gy at 1 mm depth along the central axis of the source involving 37 MBq activity is about 2.7 hrs. PMID:26150682

  5. The Key Events Dose-Response Framework: Its Potential for Application to Foodborne Pathogenic Microorganisms

    PubMed Central

    BUCHANAN, ROBERT L.; HAVELAAR, ARIE H.; SMITH, MARY ALICE; WHITING, RICHARD C.; JULIEN, ELIZABETH

    2009-01-01

    The Key Events Dose-Response Framework (KEDRF) is an analytical approach that facilitates the use of currently available data to gain insight regarding dose-response relationships. The use of the KEDRF also helps identify critical knowledge gaps that once filled, will reduce reliance on assumptions. The present study considers how the KEDRF might be applied to pathogenic microorganisms, using fetal listeriosis resulting from maternal ingestion of food contaminated with L. monocytogenes as an initial example. Major biological events along the pathway between food ingestion and the endpoint of concern are systematically considered with regard to dose (i.e., number of organisms), pathogen factors (e.g., virulence), and protective host mechanisms (e.g., immune response or other homeostatic mechanisms). It is concluded that the KEDRF provides a useful structure for systematically evaluating the complex array of host and pathogen factors that influence the dose-response relationship. In particular, the KEDRF supports efforts to specify and quantify the sources of variability, a prerequisite to strengthening the scientific basis for food safety decision making. PMID:19690997

  6. In vivo toxic and lethal cardiovascular effects of a synthetic polymeric 1,3-dodecylpyridinium salt in rodents

    SciTech Connect

    Grandic, Marjana; Sepcic, Kristina; Turk, Tom; Juntes, Polona; Frangez, Robert

    2011-08-15

    APS12-2 is one in a series of synthetic analogs of the polymeric alkylpyridinium salts isolated from the marine sponge Reniera sarai. As it is a potential candidate for treating non small cell lung cancer (NSCLC), we have studied its possible toxic and lethal effects in vivo. The median lethal dose (LD{sub 50}) of APS12-2 in mice was determined to be 11.5 mg/kg. Electrocardiograms, arterial blood pressure and respiratory activity were recorded under general anesthesia in untreated, pharmacologically vagotomized and artificially ventilated rats injected with APS12-2. In one group, the in vivo effects of APS12-2 were studied on nerve-evoked muscle contraction. Administration of APS12-2 at a dose of 8 mg/kg caused a progressive reduction of arterial blood pressure to a mid-circulatory value, accompanied by bradycardia, myocardial ischemia, ventricular extrasystoles, and second degree atrio-ventricular block. Similar electrocardiogram and arterial blood pressure changes caused by APS12-2 (8 mg/kg) were observed in animals pretreated with atropine and in artificially ventilated animals, indicating that hypoxia and cholinergic effects do not play a crucial role in the toxicity of APS12-2. Application of APS12-2 at sublethal doses (4 and 5.5 mg/kg) caused a decrease of arterial blood pressure, followed by an increase slightly above control values. We found that APS12-2 causes lysis of rat erythrocytes in vitro, therefore it is reasonable to expect the same effect in vivo. Indeed, hyperkalemia was observed in the blood of experimental animals. Hyperkalemia probably plays an important role in APS12-2 cardiotoxicity since no evident changes in histopathology of the heart were found. However, acute lesions were observed in the pulmonary vessels of rats after application of 8 mg/kg APS12-2. Predominant effects were dilation of interalveolar blood vessels and lysis of aggregated erythrocytes within their lumina. - Highlights: > LD{sub 50} estimated in mice (11.5 mg/kg) revealed

  7. Radiologic exposure conditions and resultant skin doses in application of xeroradiography to the orthodontic diagnosis

    SciTech Connect

    Nakasima, A.; Nakata, S.; Shimizu, K.; Takahama, Y.

    1980-12-01

    Xeroradiography is the recording of radiologic image by a photoelectric process rather than the photochemical one used in conventional radiography. In order to investigate the advantages and disadvantages of xeroradiography in the orthodontic field, minimum xeroradiologic exposure conditions for skull projections, joint projections, and hand projections were established by thirteen examiners and the relationship between the image production and x-ray radiation was compared with conventional film techniques. The advantages of xeroradiograph were finer and clear images caused by the edge effect and wide latitude of xeroradiography; the main hazard was the unavoidable larger skin dose required by the projection procedures. The skin doses with xeroradiography were 2.4 to 16.2 times larger than those with conventional film techniques.

  8. 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.

    PubMed

    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 < 0.05) than the linear (L) model. The usual RCS includes the L-global model but not the quadratic (Q) nor linear-quadratic (LQ) global models. The authors extended the RCS to include L or LQ global models by putting L or LQ constraints on the 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. PMID:26011495

  9. Guidelines for application of chemical-specific adjustment factors in dose/concentration-response assessment.

    PubMed

    Meek, M E; Renwick, A; Ohanian, E; Dourson, M; Lake, B; Naumann, B D; Vu, V

    2002-12-27

    This manuscript addresses guidance in the use of kinetic and dynamic data to inform quantitatively extrapolations for interspecies differences and human variability in dose-response assessment developed in a project of the International Programme on Chemical Safety (IPCS) initiative on Harmonisation of Approaches to the Assessment of Risk from Exposure to Chemicals. The guidance has been developed and refined through a series of planning and technical meetings and larger workshops of a broad range of participants from academia, government agencies and the private sector. The guidance for adequacy of data for replacement of common defaults for interspecies differences and human variability is presented in the context of several generic categories including: determination of the active chemical species, choice of the appropriate metric (kinetic components) or endpoint (dynamic components) and nature of experimental data, the latter which includes reference to the relevance of population, route and dose and the adequacy of the number of subjects/samples. The principal objective of this guidance developed primarily as a resource for risk assessors, is to foster better understanding of the components of and criteria for adequacy of chemical-specific data to quantitate interspecies differences and human variability in kinetics and dynamics. It is anticipated that this guidance will also encourage the development of appropriate data and facilitate their incorporation in a consistent fashion in dose-response assessment for regulatory purposes (IPCS, 2001). PMID:12505295

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

    PubMed

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

    2016-06-10

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

  11. Network meta-analysis models to account for variability in treatment definitions: application to dose effects.

    PubMed

    Del Giovane, Cinzia; Vacchi, Laura; Mavridis, Dimitris; Filippini, Graziella; Salanti, Georgia

    2013-01-15

    For a network meta-analysis, an interlinked network of nodes representing competing treatments is needed. It is often challenging to define the nodes as these typically refer to similar but rarely identical interventions. The objectives of this paper are as follows: (i) to present a series of network meta-analysis models that account for variation in the definition of the nodes and (ii) to exemplify the models where variation in the treatment definitions relates to the dose. Starting from the model that assumes each node has a 'fixed' definition, we gradually introduce terms to explain variability by assuming that each node has several subnodes that relate to different doses. The effects of subnodes are considered monotonic, linked with a 'random walk', random but exchangeable, or have a linear pattern around the treatment mean effect. Each model can be combined with different assumptions for the consistency of effects and might impact on the ranking of the treatments. Goodness of fit, heterogeneity and inconsistency were assessed. The models are illustrated in a star network for the effectiveness of fluoride toothpaste and in a full network comparing agents for multiple sclerosis. The fit and parsimony measures indicate that in the fluoride network the impact of the dose subnodes is important whereas in the multiple sclerosis network the model without subnodes is the most appropriate. The proposed approach can be a useful exploratory tool to explain sources of heterogeneity and inconsistency when there is doubt whether similar interventions should be grouped under the same node. PMID:22815277

  12. Detector photon response and absorbed dose and their applications to rapid triage techniques

    NASA Astrophysics Data System (ADS)

    Voss, Shannon Prentice

    As radiation specialists, one of our primary objectives in the Navy is protecting people and the environment from the effects of ionizing and non-ionizing radiation. Focusing on radiological dispersal devices (RDD) will provide increased personnel protection as well as optimize emergency response assets for the general public. An attack involving an RDD has been of particular concern because it is intended to spread contamination over a wide area and cause massive panic within the general population. A rapid method of triage will be necessary to segregate the unexposed and slightly exposed from those needing immediate medical treatment. Because of the aerosol dispersal of the radioactive material, inhalation of the radioactive material may be the primary exposure route. The primary radionuclides likely to be used in a RDD attack are Co-60, Cs-137, Ir-192, Sr-90 and Am-241. Through the use of a MAX phantom along with a few Simulink MATLAB programs, a good anthropomorphic phantom was created for use in MCNPX simulations that would provide organ doses from internally deposited radionuclides. Ludlum model 44-9 and 44-2 detectors were used to verify the simulated dose from the MCNPX code. Based on the results, acute dose rate limits were developed for emergency response personnel that would assist in patient triage.

  13. What is desirable and feasible in dose reconstruction for application in epidemiological studies?

    SciTech Connect

    Bouville, A.; Beebe, G.W.; Anspaugh, L.

    1996-02-01

    Epidemiological studies of populations are of two general forms, monitoring or formal, and serve several possible purposes. Monitoring studies inform members of potentially affected population groups of the nature and magnitude of the risks that might have been imposed on them. Formal epidemiological studies can increase scientific knowledge about the quantitative risk that attends exposure. Risks of human health due to radiation exposure are most appropriately estimated by means of formal epidemiological studies. Dosimetric data are essential for any epidemiological study, but the detail and accuracy needed depend on the purposes to be served. If the need is for a monitoring study, then general information about doses will suffice. However, a formal study that is expected to contribute to scientific information about quantitative radiation risk requires careful individual dose estimation. This paper is devoted to the discussion of dosimetric data needed for formal epidemiological studies of populations exposed as a result of nuclear power operations. The recommendations made by the National Research Council have largely been followed. The examples used in this paper are relevant to the Chernobyl accident, which caused a large number of people to be exposed at relatively high doses and provided an opportunity for formal epidemiological studies to be initiated. The studies that are singled out are those of thyroid cancer among children who resided in Belarus and in Ukraine at the time of the accident, and those of leukemia among workers involved in the mitigation of the accident and in clean-up operations.

  14. Prevalence of lethal osteochondrodysplasias in Denmark.

    PubMed

    Andersen, P E

    1989-04-01

    The point prevalence at birth of lethal osteochondrodysplasias in a subregion of Denmark was estimated by a study of all children born January 1970 through December 1983. Two cases of thanatophoric dysplasia, one case of thanatophoric dysplasia with cloverleaf skull, two cases of micromelic bone dysplasia with cloverleaf skull, two cases of achondrogenesis type III, and three cases of achondrogenesis type IV were found. Two cases were unclassifiable due to lack of radiographs. In total, the point prevalence at birth was 15.4 per 100,000. Thus lethal osteochondrodysplasias seem to be more common than is generally assumed. The clinical and radiographic findings in micromelic bone dysplasia with cloverleaf skull are discussed in relation to thanatophoric dysplasia and achondrogenesis type IV. PMID:2789000

  15. Henipaviruses-unanswered questions of lethal zoonoses.

    PubMed

    Field, Hume; Kung, Nina

    2011-12-01

    The highly lethal Hendra and Nipah viruses have been described for little more than a decade, yet within that time have been aetiologically associated with major livestock and human health impacts, albeit on a limited scale. Do these emerging pathogens pose a broader threat, or are they inconsequential 'viral chatter'. Given their lethality, and the evident multi-generational human-to-human transmission associated with Nipah virus in Bangladesh, it seems prudent to apply the precautionary principle. While much is known of their clinical, pathogenic and epidemiologic features in livestock species and humans, a number of fundamental questions regarding the relationship between the viruses, their natural fruit-bat host and the environment remain unanswered. In this paper, we pose and probe these questions in context, and offer perspectives based primarily on our experience with Hendra virus in Australia, augmented with Nipah virus parallels. PMID:22440924

  16. Synthetic lethal approaches to breast cancer therapy.

    PubMed

    Rehman, Farah L; Lord, Christopher J; Ashworth, Alan

    2010-12-01

    The promise of personalized therapy for breast cancer is that therapeutic efficacy will be increased while toxic effects are reduced to a minimum. To achieve this goal, there is now an emphasis on the design of therapies that are based not only on the clinical manifestations of the disease, but also on the underlying molecular and cellular biology of cancer. However, identifying targets for personalized therapies in breast cancer is challenging. Here, we describe how biological concepts such as synthetic lethality and oncogene addiction can be used to identify new therapeutic targets and approaches. We discuss the current clinical developments in implementing synthetic lethality therapies, and highlight new ways in which this approach could be used to target specific subsets of breast cancer. PMID:20956981

  17. Brine shrimp lethality assay of Bacopa monnieri.

    PubMed

    D'Souza, Prashanth; Deepak, Mundkinajeddu; Rani, Padmaja; Kadamboor, Sandhya; Mathew, Anjana; Chandrashekar, Arun P; Agarwal, Amit

    2002-03-01

    Successive petroleum ether, chloroform, ethanol and water extracts, a saponin rich fraction (SRF) and bacoside A isolated from Bacopa monnieri were tested for brine shrimp lethality. Successive ethanol extracts and SRF showed potent activity. Bacoside A showed the maximum activity with a LC(50) of 38.3 microg/mL. The results confirmed the previous reports of an anticancer effect of Bacopa monnieri and suggest bacoside A as the active constituent. PMID:11933129

  18. Specific ultrasonographic features of perinatal lethal hypophosphatasia.

    PubMed

    Zankl, Andreas; Mornet, Etienne; Wong, Shell

    2008-05-01

    Prenatal diagnosis of perinatal lethal hypophosphatasia (PL-HPH) by ultrasonography is difficult as PL-HPH must be differentiated from other skeletal dysplasias with short long bones and poor mineralization of the skeleton, such as osteogenesis imperfecta type II and achondrogenesis/hypochondrogenesis. Here we present a case of molecularly confirmed PL-HPH and illustrate specific ultrasonographic findings that help to distinguish PL-HPH from similar conditions. PMID:18386808

  19. Application of a radiophotoluminescent glass dosimeter to nonreference condition dosimetry in the postal dose audit system

    SciTech Connect

    Mizuno, Hideyuki Fukumura, Akifumi; Fukahori, Mai; Sakata, Suoh; Yamashita, Wataru; Takase, Nobuhiro; Yajima, Kaori; Katayose, Tetsurou; Abe-Sakama, Kyoko; Kanai, Tatsuaki; Kusano, Yohsuke; Shimbo, Munefumi

    2014-11-01

    Purpose: The purpose of this study was to obtain a set of correction factors of the radiophotoluminescent glass dosimeter (RGD) output for field size changes and wedge insertions. Methods: Several linear accelerators were used for irradiation of the RGDs. The field sizes were changed from 5 × 5 cm to 25 × 25 cm for 4, 6, 10, and 15 MV x-ray beams. The wedge angles were 15°, 30°, 45°, and 60°. In addition to physical wedge irradiation, nonphysical (dynamic/virtual) wedge irradiations were performed. Results: The obtained data were fitted with a single line for each energy, and correction factors were determined. Compared with ionization chamber outputs, the RGD outputs gradually increased with increasing field size, because of the higher RGD response to scattered low-energy photons. The output increase was about 1% per 10 cm increase in field size, with a slight difference dependent on the beam energy. For both physical and nonphysical wedged beam irradiation, there were no systematic trends in the RGD outputs, such as monotonic increase or decrease depending on the wedge angle change if the authors consider the uncertainty, which is approximately 0.6% for each set of measured points. Therefore, no correction factor was needed for all inserted wedges. Based on this work, postal dose audits using RGDs for the nonreference condition were initiated in 2010. The postal dose audit results between 2010 and 2012 were analyzed. The mean difference between the measured and stated doses was within 0.5% for all fields with field sizes between 5 × 5 cm and 25 × 25 cm and with wedge angles from 15° to 60°. The standard deviations (SDs) of the difference distribution were within the estimated uncertainty (1SD) except for the 25 × 25 cm field size data, which were not reliable because of poor statistics (n = 16). Conclusions: A set of RGD output correction factors was determined for field size changes and wedge insertions. The results obtained from recent postal dose

  20. The population genetics of synthetic lethals.

    PubMed

    Phillips, P C; Johnson, N A

    1998-09-01

    Synthetic lethals are variants at different loci that have little or no effect on viability singly but cause lethality in combination. The importance of synthetic lethals and, more generally, of synthetic deleterious loci (SDL) has been controversial. Here, we derive the expected frequencies for SDL under a mutation-selection balance for the complete haploid model and selected cases of the diploid model. We have also obtained simple approximations that demonstrate good fit to exact solutions based on numerical iterations. In the haploid case, equilibrium frequencies of carrier haplotypes (individuals with only a single mutation) are comparable to analogous single-locus results, after allowing for the effects of linkage. Frequencies in the diploid case, however, are much higher and more comparable to the square root of the single-locus results. In particular, when selection operates only on the double-mutant homozygote and linkage is not too tight, the expected frequency of the carriers is approximately the quartic root of the ratio between the mutation rate and the selection coefficient of the synthetics. For a reasonably wide set of models, the frequencies of carriers can be on the order of a few percent. The equilibrium frequencies of these deleterious alleles can be relatively high because, with SDL, both dominance and epistasis act to shield carriers from exposure to selection. We also discuss the possible role of SDL in maintaining genetic variation and in hybrid breakdown. PMID:9725860

  1. Lethal Interpersonal Violence in the Middle Pleistocene

    PubMed Central

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M.; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin. PMID:26018668

  2. Lethal interpersonal violence in the Middle Pleistocene.

    PubMed

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald

    2015-01-01

    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin. PMID:26018668

  3. The development and application of the visible Chinese human model for Monte Carlo dose calculations.

    PubMed

    Zhang, Guozhi; Luo, Qingming; Zeng, Shaoqun; Liu, Qian

    2008-02-01

    A new whole-body computational phantom, the Visible Chinese Human (VCH), was developed using high-resolution transversal photographs of a Chinese adult male cadaver. Following the segmentation and tridimensional reconstruction, a voxel-based model that faithfully represented the average anatomical characteristics of the Chinese population was established for radiation dosimetry. The vascular system of VCH was fully preserved, and the cadaver specimen was processed in the standing posture. A total of 8,920 slices were obtained by continuous sectioning at 0.2 mm intervals, and 48 organs and tissues were segmented from the tomographic color images at 5440 x 4080 pixel resolution, corresponding to a voxel size of 0.1 x 0.1 x 0.2 mm3. The resulting VCH computational phantom, consisting of 230 x 120 x 892 voxels with a unit volume of 2 x 2 x 2 mm3, was ported into Monte Carlo code MCNPX2.5 to calculate the conversion coefficients from kerma free-in-air to absorbed dose and to effective dose for external monoenergetic photon beams from 15 keV to 10 MeV under six idealized external irradiation geometries (anterior-posterior, posterior-anterior, left lateral, right lateral, rotational, and isotropic). Organ masses of the VCH model are fairly different from other human phantoms. Differences of up to 300% are observed between doses from ICRP 74 data and those of VIP-Man. Detailed information from the VCH model is able to improve the radiological datasets, particular for the Chinese population, and provide insights into the research of various computational phantoms. PMID:18188046

  4. Pharmacokinetics of difloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications.

    PubMed

    Ding, H Z; Yang, G X; Huang, X H; Chen, Z L; Zeng, Z L

    2008-06-01

    Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t(1/2beta)) were 17.14 +/- 4.14, 25.79 +/- 8.10, 16.67 +/- 4.04 (pigs) and 6.11 +/- 1.50, 5.64 +/- 0.74, 8.20 +/- 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (C(max)) of 1.77 +/- 0.66, 2.29 +/- 0.85 (pigs) and 2.51 +/- 0.36, 1.00 +/- 0.21 microg/mL (broilers) attained at t(max) of 1.29 +/- 0.26, 1.41 +/- 0.88 (pigs) and 0.86 +/- 0.4, 4.34 +/- 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 +/- 28.9)% and (105.7 +/- 37.1)% (pigs) and (77.0 +/- 11.8)% and (54.2 +/- 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(V(d(area))) of 4.91 +/- 1.88 and 3.10 +/- 0.67 L/kg and total body clearances(Cl(B)) of 0.20 +/- 0.06 and 0.37 +/- 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t(1/2ka), t(1/2alpha)) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC(90) are <0.25 microg/mL and <0.1 microg/mL respectively. PMID:18471140

  5. Radiation dose reduction with application of non-linear adaptive filters for abdominal CT

    PubMed Central

    Singh, Sarabjeet; Kalra, Mannudeep K; Sung, Mi Kim; Back, Anni; Blake, Michael A

    2012-01-01

    AIM: To evaluate the effect of non-linear adaptive filters (NLAF) on abdominal computed tomography (CT) images acquired at different radiation dose levels. METHODS: Nineteen patients (mean age 61.6 ± 7.9 years, M:F = 8:11) gave informed consent for an Institutional Review Board approved prospective study involving acquisition of 4 additional image series (200, 150, 100, 50 mAs and 120 kVp) on a 64 slice multidetector row CT scanner over an identical 10 cm length in the abdomen. The CT images acquired at 150, 100 and 50 mAs were processed with the NLAF. Two radiologists reviewed unprocessed and processed images for image quality in a blinded randomized manner. CT dose index volume, dose length product, patient weight, transverse diameters, objective noise and CT numbers were recorded. Data were analyzed using Analysis of Variance and Wilcoxon signed rank test. RESULTS: Of the 31 lesions detected in abdominal CT images, 28 lesions were less than 1 cm in size. Subjective image noise was graded as unacceptable in unprocessed images at 50 and 100 mAs, and in NLAF processed images at 50 mAs only. In NLAF processed images, objective image noise was decreased by 21% (14.4 ± 4/18.2 ± 4.9) at 150 mAs, 28.3% (15.7 ± 5.6/21.9 ± 4) at 100 mAs and by 39.4% (18.8 ± 9/30.4 ± 9.2) at 50 mAs compared to unprocessed images acquired at respective radiation dose levels. At 100 mAs the visibility of smaller structures improved from suboptimal in unprocessed images to excellent in NLAF processed images, whereas diagnostic confidence was respectively improved from probably confident to fully confident. CONCLUSION: NLAF lowers image noise, improves the visibility of small structures and maintains lesion conspicuity at down to 100 mAs for abdominal CT. PMID:22328968

  6. Development of the voxel computational phantoms of pediatric patients and their application to organ dose assessment

    NASA Astrophysics Data System (ADS)

    Lee, Choonik

    A series of realistic voxel computational phantoms of pediatric patients were developed and then used for the radiation risk assessment for various exposure scenarios. The high-resolution computed tomographic images of live patients were utilized for the development of the five voxel phantoms of pediatric patients, 9-month male, 4-year female, 8-year female, 11-year male, and 14-year male. The phantoms were first developed as head and torso phantoms and then extended into whole body phantoms by utilizing computed tomographic images of a healthy adult volunteer. The whole body phantom series was modified to have the same anthropometrics with the most recent reference data reported by the international commission on radiological protection. The phantoms, named as the University of Florida series B, are the first complete set of the pediatric voxel phantoms having reference organ masses and total heights. As part of the dosimetry study, the investigation on skeletal tissue dosimetry methods was performed for better understanding of the radiation dose to the active bone marrow and bone endosteum. All of the currently available methodologies were inter-compared and benchmarked with the paired-image radiation transport model. The dosimetric characteristics of the phantoms were investigated by using Monte Carlo simulation of the broad parallel beams of external phantom in anterior-posterior, posterior-anterior, left lateral, right lateral, rotational, and isotropic angles. Organ dose conversion coefficients were calculated for extensive photon energies and compared with the conventional stylized pediatric phantoms of Oak Ridge National Laboratory. The multi-slice helical computed tomography exams were simulated using Monte Carlo simulation code for various exams protocols, head, chest, abdomen, pelvis, and chest-abdomen-pelvis studies. Results have found realistic estimates of the effective doses for frequently used protocols in pediatric radiology. The results were very

  7. Effect of UV irradiation on lethal infection of mice with Candida albicans.

    PubMed

    Denkins, Y M; Kripke, M L

    1993-02-01

    Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicans in the kidneys, in contrast to sensitized, unirradiated mice. PMID:8451288

  8. Less-lethal munitions as extended-range impact weapons

    NASA Astrophysics Data System (ADS)

    Hubbs, Ken

    1997-01-01

    With the proliferation of 'suicide by cop' incidents, the concept of less lethal (LL) impact munitions has definitely caught on. There is much to be said for sterile laboratory testing and wound ballistic studies, but having 'real world' operational data is invaluable. Two years ago, a data base was set up to collect this information. The data base continues to grow with incidents from a cross the country and others pursued internationally. Indications are that LL munitions deliver a similar amount of force as conventional police impact weapons i.e., police batons, PR-24's, nunchakus, etc. One advantage over conventional impact weapons, is that LL munitions can be used at much greater distances from a suspect or crown of rioters. This gave rise to the term: extended range impact weapons. Having the ability to examine numerous cases in which these LL munitions have been successfully used for the resolution of critical incidents, is beneficial in evaluating the application and defending the usage of these force options. This paper examines 187 less lethal shootings and discusses such things as: the distance the munitions were fired, the types of injuries sustained by the targeted suspect, the body area of impact, what, if any weapons the suspect was armed with, and the type of incident requiring police response.

  9. Engineered female-specific lethality for control of pest Lepidoptera.

    PubMed

    Jin, Li; Walker, Adam S; Fu, Guoliang; Harvey-Samuel, Timothy; Dafa'alla, Tarig; Miles, Andrea; Marubbi, Thea; Granville, Deborah; Humphrey-Jones, Nerys; O'Connell, Sinead; Morrison, Neil I; Alphey, Luke

    2013-03-15

    The sterile insect technique (SIT) is a pest control strategy involving the mass release of radiation-sterilized insects, which reduce the target population through nonviable matings. In Lepidoptera, SIT could be more broadly applicable if the deleterious effects of sterilization by irradiation could be avoided. Moreover, male-only release can improve the efficacy of SIT. Adequate methods of male-only production in Lepidoptera are currently lacking, in contrast to some Diptera. We describe a synthetic genetic system that allows male-only moth production for SIT and also replaces radiation sterilization with inherited female-specific lethality. We sequenced and characterized the doublesex (dsx) gene from the pink bollworm (Pectinophora gossypiella). Sex-alternate splicing from dsx was used to develop a conditional lethal genetic sexing system in two pest moths: the diamondback moth (Plutella xylostella) and pink bollworm. This system shows promise for enhancing existing pink bollworm SIT, as well as broadening SIT-type control to diamondback moth and other Lepidoptera. PMID:23802263

  10. The development of early pediatric models and their application to radiation absorbed dose calculations

    SciTech Connect

    Poston, J.W.

    1989-01-01

    This presentation will review and describe the development of pediatric phantoms for use in radiation dose calculations . The development of pediatric models for dose calculations essentially paralleled that of the adult. In fact, Snyder and Fisher at the Oak Ridge National Laboratory reported on a series of phantoms for such calculations in 1966 about two years before the first MIRD publication on the adult human phantom. These phantoms, for a newborn, one-, five-, ten-, and fifteen-year old, were derived from the adult phantom. The pediatric'' models were obtained through a series of transformations applied to the major dimensions of the adult, which were specified in a Cartesian coordinate system. These phantoms suffered from the fact that no real consideration was given to the influence of these mathematical transformations on the actual organ sizes in the other models nor to the relation of the resulting organ masses to those in humans of the particular age. Later, an extensive effort was invested in designing individual'' pediatric phantoms for each age based upon a careful review of the literature. Unfortunately, the phantoms had limited use and only a small number of calculations were made available to the user community. Examples of the phantoms, their typical dimensions, common weaknesses, etc. will be discussed.