Phylogenetic relationships of Malaysia's long-tailed macaques, Macaca fascicularis, based on cytochrome b sequences.

PubMed

Abdul-Latiff, Muhammad Abu Bakar; Ruslin, Farhani; Fui, Vun Vui; Abu, Mohd-Hashim; Rovie-Ryan, Jeffrine Japning; Abdul-Patah, Pazil; Lakim, Maklarin; Roos, Christian; Yaakop, Salmah; Md-Zain, Badrul Munir

2014-01-01

Phylogenetic relationships among Malaysia's long-tailed macaques have yet to be established, despite abundant genetic studies of the species worldwide. The aims of this study are to examine the phylogenetic relationships of Macaca fascicularis in Malaysia and to test its classification as a morphological subspecies. A total of 25 genetic samples of M. fascicularis yielding 383 bp of Cytochrome b (Cyt b) sequences were used in phylogenetic analysis along with one sample each of M. nemestrina and M. arctoides used as outgroups. Sequence character analysis reveals that Cyt b locus is a highly conserved region with only 23% parsimony informative character detected among ingroups. Further analysis indicates a clear separation between populations originating from different regions; the Malay Peninsula versus Borneo Insular, the East Coast versus West Coast of the Malay Peninsula, and the island versus mainland Malay Peninsula populations. Phylogenetic trees (NJ, MP and Bayesian) portray a consistent clustering paradigm as Borneo's population was distinguished from Peninsula's population (99% and 100% bootstrap value in NJ and MP respectively and 1.00 posterior probability in Bayesian trees). The East coast population was separated from other Peninsula populations (64% in NJ, 66% in MP and 0.53 posterior probability in Bayesian). West coast populations were divided into 2 clades: the North-South (47%/54% in NJ, 26/26% in MP and 1.00/0.80 posterior probability in Bayesian) and Island-Mainland (93% in NJ, 90% in MP and 1.00 posterior probability in Bayesian). The results confirm the previous morphological assignment of 2 subspecies, M. f. fascicularis and M. f. argentimembris, in the Malay Peninsula. These populations should be treated as separate genetic entities in order to conserve the genetic diversity of Malaysia's M. fascicularis. These findings are crucial in aiding the conservation management and translocation process of M. fascicularis populations in Malaysia.

Biosorption and desorption of Cd2+ from wastewater by dehydrated shreds of Cladophora fascicularis

NASA Astrophysics Data System (ADS)

Deng, Liping; Zhu, Xiaobin; Su, Yingying; Su, Hua; Wang, Xinting

2008-02-01

The adsorption and desorption of algae Cladophora fascicularis and their relation with initial Cd2+ concentration, initial pH, and co-existing ions were studied. Adsorption equilibrium and biosorption kinetics were established from batch experiments. The adsorption equilibrium was adequately described by the Langmuir isotherm, and biosorption kinetics was in pseudo-second order model. The experiment on co-existing ions showed that the biosorption capacity of biomass decreased with an increasing concentration of competing ions. Desorption experiments indicated that EDTA was efficient desorbent for recovery from Cd2+. With high capacities of metal biosorption and desorption, the biomass of Cladophora fascicularis is promising as a cost-effective biosorbent for the removal of Cd2+ from wastewater.

Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

2016-01-01

Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

Visible lesion laser thresholds in Cynomolgus (Macaca fascicularis) retina with a 1064 nm 12-ns pulsed laser

NASA Astrophysics Data System (ADS)

Oliver, Jeffrey W.; Stolarski, David J.; Noojin, Gary D.; Hodnett, Harvey M.; Imholte, Michelle L.; Rockwell, Benjamin A.; Kumru, Semih S.

2007-02-01

A series of experiments in a new animal model for retinal damage, cynomolgus monkeys (Macaca fascicularis), have been conducted to determine the damage threshold for 12.5-nanosecond laser exposures at 1064 nm. These results provide a direct comparison to threshold values obtained in rhesus monkey (Macaca mulatta), which is the model historically used in establishing retinal maximum permissible exposure (MPE) limits. In this study, the irradiance level of a collimated Gaussian laser beam of 2.5 mm diameter at the cornea was randomly varied to produce a rectangular grid of exposures on the retina. Exposures sites were fundoscopically evaluated at post-irradiance intervals of 1 hour and 24 hours. Probit analysis was performed on dose-response data to obtain probability of response curves. The 50% probability of damage (ED50) values for 1 and 24 hours post-exposure are 28.5(22.7-38.4) μJ and 17.0(12.9-21.8) μJ, respectively. These values compare favorably to data obtained with the rhesus model, 28.7(22.3-39.3) μJ and 19.1(13.6-24.4) μJ, suggesting that the cynomolgus monkey may be a suitable replacement for rhesus monkey in photoacoustic minimum visible lesion threshold studies.

Beneficial Use of Dredged Material Monitoring Program. 1996 Annual report (Base Year Through Fy1996).

DTIC Science & Technology

1997-01-01

Echinochloa walteri _ Panicum dichotomiflorum _ Leptochloa fascicularis Cynodon dactylon Paspalum distichum Suaeda linearis Xanthium strumarium ...fascicularis Cynodon dactylon Paspalum distichum Salicornia bigelovii Atriplex pentandra Suaeda linearis Conyza canadensis Xanthium strumarium ...marshes, low fields Xanthium strumarium L cocklebur annual; waste places, old fields, pond shores, ditches, stable dune areas, beaches 5A-6 U.S

Stimulus-Food Pairings Produce Stimulus-Directed Touch Screen Responding in Cynomolgus Monkeys ("Macaca Fascicularis") with or without a Positive Response Contingency

ERIC Educational Resources Information Center

Bullock, Christopher E.; Myers, Todd M.

2009-01-01

Acquisition and maintenance of touch-screen responding was examined in naive cynomolgus monkeys ("Macaca fascicularis") under automaintenance and classical conditioning arrangements. In the first condition of Experiment 1, we compared acquisition of screen touching to a randomly positioned stimulus (a gray square) that was either stationary or…

Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

PubMed Central

2011-01-01

Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk. PMID:21999700

Evaluation of bendectin embryotoxicity in nonhuman primates: II. Double-blind study in term cynomolgus monkeys.

PubMed

Hendrickx, A G; Cukierski, M; Prahalada, S; Janos, G; Booher, S; Nyland, T

1985-10-01

The embryotoxic and teratogenic potential of Bendectin was assessed in this double-blind study in the cynomolgus monkey (Macaca fascicularis). Bendectin was administered orally at doses approximately two, five, and 20 times the human dose equivalent from 22 +/- 2 through 50 days of gestation. Fetuses were delivered by cesarean section near term and examined for malformations. There was no maternal toxicity as evidenced by maternal weights and physical signs. There was no correlation between dosage and the number of prenatal deaths. No significant abnormalities related to treatment were observed in postdelivery physical examinations, placental evaluations, external and internal gross examinations, or from radiographs of the neonates. Under the conditions of this study the treatment of pregnant cynomolgus monkeys with Bendectin produced no evidence of teratogenicity or embryo-, or fetal-, or maternal toxicity.

RNA-Seq Reveals Extensive Transcriptional Response to Heat Stress in the Stony Coral Galaxea fascicularis

PubMed Central

Hou, Jing; Xu, Tao; Su, Dingjia; Wu, Ying; Cheng, Li; Wang, Jun; Zhou, Zhi; Wang, Yan

2018-01-01

Galaxea fascicularis, a stony coral belonging to family Oculinidae, is widely distributed in Red Sea, the Gulf of Aden and large areas of the Indo-Pacific oceans. So far there is a lack of gene expression knowledge concerning this massive coral. In the present study, G. fascicularis was subjected to heat stress at 32.0 ± 0.5°C in the lab, we found that the density of symbiotic zooxanthellae decreased significantly; meanwhile apparent bleaching and tissue lysing were observed at 10 h and 18 h after heat stress. The transcriptome responses were investigated in the stony coral G. fascicularis during heat bleaching using RNA-seq. A total of 42,028 coral genes were assembled from over 439 million reads. Gene expressions were compared at 10 and 18 h after heat stress. The significantly upregulated genes found in the Control_10h vs. Heat_10h comparison, presented mainly in GO terms related with DNA integration and unfolded protein response; and for the Control_18h vs. Heat_18h comparison, the GO terms include DNA integration. In addition, comparison between groups of Control_10h vs. Heat_10h and Control_18h vs. Heat_18h revealed that 125 genes were significantly upregulated in common between the two groups, whereas 21 genes were significantly downregulated in common, all these differentially expressed genes were found to be involved in stress response, DNA integration and unfolded protein response. Taken together, our results suggest that high temperature could activate the stress response at the early stage, and subsequently induce the bleaching and lysing through DNA integration and unfolded protein response, which are able to disrupt the balance of coral-zooxanthella symbiosis in the stony coral G. fascicularis. PMID:29487614

Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis).

PubMed

Colagross-Schouten, Angela M; Canfield, Don R

2015-12-01

A 20-y-old female cynomolgus macaque (Macaca fascicularis) housed in an indoor primate facility presented for poor appetite and acute weakness after several years of no adverse health events. Physical examination revealed a firm, ovoid mass in the caudal abdomen. Further evaluation revealed the mass to be a vaginal calculus composed of calcium carbonate, apatite, and struvite. To our knowledge, this case is the first reported description of a vaginal stone in an NHP.

Allometry and Interspecific Differences in the Facial Cranium of Two Closely Related Macaque Species

PubMed Central

Ito, Tsuyoshi; Nishimura, Takeshi; Takai, Masanaru

2011-01-01

Interpreting evolutionary history of macaque monkeys from fossil evidence is difficult, because their evolutionary fluctuations in body size might have removed or formed important morphological features differently in each lineage. We employed geometric morphometrics to explore allometric trajectories of craniofacial shape in two closely related species, Macaca fascicularis and M. fuscata. These two species exhibit a single shared allometric trajectory in superoinferior deflection of the anterior face, indicating that the differences in this feature can be explained by size variation. In contrast, two parallel trajectories are demonstrated in craniofacial protrusion, indicating that even if they are comparable in size, M. fuscata has a higher and shorter face than M. fascicularis. The degree of facial protrusion is most likely a critical feature for phyletic evaluation in the fascicularis group. Such analyses in various macaques would help to resolve controversies regarding phyletic interpretations of fossil macaques. PMID:22567301

Effect of methylmercury on acetylcholinestrase and serum cholinesterase activity in monkeys, Macaca fascicularis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petruccioli, L.; Turillazzi, P.G.

1991-05-01

The consumption of fish and fish-derived products is the main pathway of human exposure to methylmercury (MeHg). Methylmercury levels vary widely in fish, depending on age, size, the position of the species in the food chain, and most of all, on pollution levels. MeHg affects the Acetylcholinesterase activity (AChE) and the serum Cholinesterase activity (BChE). Histoenzymatic studies showed that 100mg Methyoxyethylmercury chloride administered for 6 days to rats caused a reduction of AChE activity in the thalamus and an increase in different parts of the nervous central system. The present study aims at verifying whether the dose permitted by F.A.O.more » and doses 10 and 100 fold higher affect the Cholinesterase activity in primates, and whether there is a correlation between AChE and BChE.« less

Analysis of the Macaca mulatta transcriptome and the sequence divergence between Macaca and human.

PubMed

Magness, Charles L; Fellin, P Campion; Thomas, Matthew J; Korth, Marcus J; Agy, Michael B; Proll, Sean C; Fitzgibbon, Matthew; Scherer, Christina A; Miner, Douglas G; Katze, Michael G; Iadonato, Shawn P

2005-01-01

We report the initial sequencing and comparative analysis of the Macaca mulatta transcriptome. Cloned sequences from 11 tissues, nine animals, and three species (M. mulatta, M. fascicularis, and M. nemestrina) were sampled, resulting in the generation of 48,642 sequence reads. These data represent an initial sampling of the putative rhesus orthologs for 6,216 human genes. Mean nucleotide diversity within M. mulatta and sequence divergence among M. fascicularis, M. nemestrina, and M. mulatta are also reported.

Transcriptome profiling of Galaxea fascicularis and its endosymbiont Symbiodinium reveals chronic eutrophication tolerance pathways and metabolic mutualism between partners

PubMed Central

Lin, Zhenyue; Chen, Mingliang; Dong, Xu; Zheng, Xinqing; Huang, Haining; Xu, Xun; Chen, Jianming

2017-01-01

In the South China Sea, coastal eutrophication in the Beibu Gulf has seriously threatened reef habitats by subjecting corals to chronic physiological stress. To determine how coral holobionts may tolerate such conditions, we examined the transcriptomes of healthy colonies of the galaxy coral Galaxea fascicularis and its endosymbiont Symbiodinium from two reef sites experiencing pristine or eutrophied nutrient regimes. We identified 236 and 205 genes that were differentially expressed in eutrophied hosts and symbionts, respectively. Both gene sets included pathways related to stress responses and metabolic interactions. An analysis of genes originating from each partner revealed striking metabolic integration with respect to vitamins, cofactors, amino acids, fatty acids, and secondary metabolite biosynthesis. The expression levels of these genes supported the existence of a continuum of mutualism in this coral-algal symbiosis. Additionally, large sets of transcription factors, cell signal transduction molecules, biomineralization components, and galaxin-related proteins were expanded in G. fascicularis relative to other coral species. PMID:28181581

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

PubMed

Kuno, S; Mizuta, E; Nishida, J; Takechi, M

1992-10-01

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

The rhesus (Macaca mulatta) and crab-eating (Macaca fascicularis) monkeys in cardiovascular and aerospace research

NASA Technical Reports Server (NTRS)

Erickson, H. H.; Ritzman, J. R.

1977-01-01

Two nonhuman primate species were used to investigate the effects of gravitoinertial forces on pilot incapacitation and performance impairment, to define human physiologic tolerance and safe exposure limits to these environments, and to obtain data which can be used to evolve new methods to improve man's G tolerance to match the structural capability of new generation aircraft. The macaca fascicularis was used to study the effects of environmental stress and atheroscelerosis on cerebral blood flow and function agents on myocardial and cardiovascular function were studied in the macaca mulatta.

The role of anthropic, ecological, and social factors in sleeping site choice by long-tailed macaques (Macaca fascicularis).

PubMed

Brotcorne, Fany; Maslarov, Cindy; Wandia, I Nengah; Fuentes, Agustin; Beudels-Jamar, Roseline C; Huynen, Marie-Claude

2014-12-01

When choosing their sleeping sites, primates make adaptive trade-offs between various biotic and abiotic constraints. In human-modified environments, anthropic factors may play a role. We assessed the influence of ecological (predation), social (intergroup competition), and anthropic (proximity to human settlements) factors in sleeping site choice by long-tailed macaques (Macaca fascicularis) occupying a habitat at the interface of natural forests and human-modified zones in Bali Barat National Park, Indonesia. Over the course of 56 nights, we collected data relating to physical features of sleeping trees, patterns of the use of sleeping sites within the home range, pre-sleep behavior, diurnal ranging patterns and availability of natural and human food. Overall, the macaques used 17 sleeping sites with 37 sleeping trees. When the monkeys slept in forest zones, they selected sleeping trees that had larger trunks but were not significantly taller than surrounding trees. Though the macaques rarely re-used sleeping sites on consecutive nights, they frequently re-used four sites over the study period. The group favored sleeping within the core area of its home range, despite the occurrence of frequent agonistic intergroup encounters there. Macaques preferentially selected sleeping trees located within or near human-modified zones, especially when human food was abundant and natural food was scarce. These results partially support the hypothesis that long-tailed macaques choose their sleeping sites to avoid predation; proximity to human settlements appears to be the primary factor influencing sleeping site choice in this primate species. Our results reflect the strong influence that anthropic factors have on primates, which subsist in increasingly human-dominated landscapes. © 2014 Wiley Periodicals, Inc.

Polar lipid composition of mammalian hair.

PubMed

Wix, M A; Wertz, P W; Downing, D T

1987-01-01

The types and amounts of polar lipids from the hair of monkey (Macacca fascicularis), dog (Canis familiaris), pig (Sus scrofa) and porcupine (Erethizon dorsatum) have been determined by quantitative thin-layer chromatography. The polar lipid content of the hair samples ranged from 0.6 to 1.6 wt%. Lipid compositions included ceramides (57-63% of the polar lipid by weight), glycosphingolipids (7-9%) and cholesteryl sulfate (22-29%). Several minor components (4-7%) remain unidentified. The results suggest that cholesteryl sulfate may be an important determinant of the cohesiveness of hair.

Infectivity titration of a prototype strain of hepatitis E virus in cynomolgus monkeys.

PubMed

Tsarev, S A; Tsareva, T S; Emerson, S U; Yarbough, P O; Legters, L J; Moskal, T; Purcell, R H

1994-06-01

The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive. The infectivity titer of SAR-55 was 10(6) cynomolgus 50% infectious doses per gram of feces. The infectivity titer corresponded to the HEV genome titer of the inoculum as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HEV IgM was detected in only a portion of the animals that had an anti-HEV IgG response. Biochemical evidence of hepatitis was most prominent in animals that were inoculated with the higher concentrations of virus and the incubation period to seroconversion was prolonged in animals that received the lower doses.

Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis.

PubMed

Huang, Xinping; Li, Min; Xu, Bo; Zhu, Xiaobin; Deng, Zhiwei; Lin, Wenhan

2007-03-21

Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF-alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed.

Temperature shapes coral-algal symbiosis in the South China Sea

NASA Astrophysics Data System (ADS)

Tong, Haoya; Cai, Lin; Zhou, Guowei; Yuan, Tao; Zhang, Weipeng; Tian, Renmao; Huang, Hui; Qian, Pei-Yuan

2017-01-01

With the increase in sea surface temperature (SST), scleractinian corals are exposed to bleaching threats but may possess certain flexibilities in terms of their associations with symbiotic algae. Previous studies have shown a close symbiosis between coral the and Symbiodinium; however, the spatial variation of the symbiosis and the attribution underlying are not well understood. In the present study, we examined coral-algal symbiosis in Galaxea fascicularis and Montipora spp. from three biogeographic regions across ~10° of latitude in the South China Sea. Analysis of similarities (ANOSIM) indicated a highly flexible coral-algal symbiosis in both G. fascicularis and Montipora spp. and canonical correspondence analysis (CCA) showed that temperature explained 83.2% and 60.1% of the explanatory subclade variations in G. fascicularis and Montipora spp., respectively, which suggested that temperature was the main environmental factor contributing to the diversity of Symbiodinium across the three regions. The geographic specificity of the Symbiodinium phylogeny was identified, revealing possible environmental selection across the three regions. These results suggest that scleractinian corals may have the ability to regulate Symbiodinium community structures under different temperatures and thus be able to adapt to gradual climate change.

Temperature shapes coral-algal symbiosis in the South China Sea

PubMed Central

Tong, Haoya; Cai, Lin; Zhou, Guowei; Yuan, Tao; Zhang, Weipeng; Tian, Renmao; Huang, Hui; Qian, Pei-Yuan

2017-01-01

With the increase in sea surface temperature (SST), scleractinian corals are exposed to bleaching threats but may possess certain flexibilities in terms of their associations with symbiotic algae. Previous studies have shown a close symbiosis between coral the and Symbiodinium; however, the spatial variation of the symbiosis and the attribution underlying are not well understood. In the present study, we examined coral-algal symbiosis in Galaxea fascicularis and Montipora spp. from three biogeographic regions across ~10° of latitude in the South China Sea. Analysis of similarities (ANOSIM) indicated a highly flexible coral-algal symbiosis in both G. fascicularis and Montipora spp. and canonical correspondence analysis (CCA) showed that temperature explained 83.2% and 60.1% of the explanatory subclade variations in G. fascicularis and Montipora spp., respectively, which suggested that temperature was the main environmental factor contributing to the diversity of Symbiodinium across the three regions. The geographic specificity of the Symbiodinium phylogeny was identified, revealing possible environmental selection across the three regions. These results suggest that scleractinian corals may have the ability to regulate Symbiodinium community structures under different temperatures and thus be able to adapt to gradual climate change. PMID:28084322

Comparison of rectal and infrared thermometry for obtaining body temperature in cynomolgus macaques (Macaca fascicularis).

PubMed

Sikoski, P; Banks, M L; Gould, R; Young, R W; Wallace, J M; Nader, M A

2007-12-01

It would be clinically advantageous to develop a method of body temperature evaluation in cynomolgus macaques (Macaca fascicularis) that did not require sedation, restraint, surgical manipulation, or expensive equipment. Body temperatures of 51 cynomolgus macaques were taken with rectal thermometry and non-contact infrared thermometry (NIFT) on the shoulder, face, abdomen, and axillary region. Body temperature measurements from NIFT were statistically different (P < 0.0001) from rectal thermometry. In addition, there was greater between- and within-subject variability in values using NIFT. There was no correlation between any sites of the NIFT and rectal thermometry. It was concluded that NIFT was not a valid alternative to rectal thermometry in cynomolgus macaques.

Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study.

PubMed

Barro, Ana M Bada; Rivero, Arianna Iglesias; Goñi, Avelina León; Navarro, Bárbara O González; Angarica, Meilis Mesa; Ramírez, Belinda Sánchez; Bedoya, Darel Martínez; Triana, Consuelo González; Rodríguez, Axel Mancebo; Parada, Ángel Casacó

2012-12-17

Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n=12). Local reactions were observed at the administration site of four treated animals (n=6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Interactive effects of oxygen, carbon dioxide and flow on photosynthesis and respiration in the scleractinian coral Galaxea fascicularis.

PubMed

Osinga, Ronald; Derksen-Hooijberg, Marlous; Wijgerde, Tim; Verreth, Johan A J

2017-06-15

Rates of dark respiration and net photosynthesis were measured for six replicate clonal fragments of the stony coral Galaxea fascicularis (Linnaeus 1767), which were incubated under 12 different combinations of dissolved oxygen (20%, 100% and 150% saturation), dissolved carbon dioxide (9.5 and 19.1 µmol l -1 ) and water flow (1-1.6 versus 4-13 cm s -1 ) in a repeated measures design. Dark respiration was enhanced by increased flow and increased oxygen saturation in an interactive way, which relates to improved oxygen influx into the coral tissue. Oxygen saturation did not influence net photosynthesis: neither hypoxia nor hyperoxia affected net photosynthesis, irrespective of flow and pH, which suggests that hyperoxia does not induce high rates of photorespiration in this coral. Flow and pH had a synergistic effect on net photosynthesis: at high flow, a decrease in pH stimulated net photosynthesis by 14%. These results indicate that for this individual of G. fascicularis , increased uptake of carbon dioxide rather than increased efflux of oxygen explains the beneficial effect of water flow on photosynthesis. Rates of net photosynthesis measured in this study are among the highest ever recorded for scleractinian corals and confirm a strong scope for growth. © 2017. Published by The Company of Biologists Ltd.

Tracing the phylogeographic history of Southeast Asian long-tailed macaques through mitogenomes of museum specimens.

PubMed

Yao, Lu; Li, Hongjie; Martin, Robert D; Moreau, Corrie S; Malhi, Ripan S

2017-11-01

The biogeographical history of Southeast Asia is complicated due to the continuous emergences and disappearances of land bridges throughout the Pleistocene. Here, we use long-tailed macaques (Macaca fascicularis), which are widely distributed throughout the mainland and islands of Southeast Asia, asa model for better understanding the biogeographical patterns of diversification in this geographically complex region. A reliable intraspecific phylogeny including individuals from localities on oceanic islands, continental islands, and the mainland is needed to trace relatedness along with the pattern and timing of colonization in this region. We used high-throughput sequencing techniques to sequence mitochondrial genomes (mitogenomes) from 95 Southeast Asian M. fascicularis specimens housed at natural history museums around the world. To achieve a comprehensive picture, we more than tripled the mitogenome sample size for M. fascicularis from previous studies, and for the first time included documented samples from the Philippines and several small Indonesian islands. Confirming the result from a previous, recent intraspecific phylogeny for M. fascicularis, the newly reconstructed phylogeny of 135 specimens divides the samples into two major clades: Clade A includes haplotypes from the mainland and some from northern Sumatra, while Clade B includes all insular haplotypes along with lineages from southern Sumatra. This study resolves a previous disparity by revealing a disjunction in the origin of Sumatran macaques, with separate lineages originating within the two major clades, suggesting that at least two major migrations to Sumatra occurred. However, our dated phylogeny reveals that the two major clades split ∼1.88Ma, which is earlier than in previously published phylogenies. Our new data reveal that most Philippine macaque lineages diverged from the Borneo stock within the last ∼0.06-0.43Ma. Finally, our study provides insight into successful sequencing of DNA across museums and shotgun sequencing of DNA specimens asa method to sequence the mitogenome. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of ethanol on cocaine self-administration in monkeys responding under a second-order schedule of reinforcement.

PubMed

John, William S; Nader, Michael A

2017-01-01

Concurrent alcohol use among cocaine abusers is common but the behavioral variables that promote co-abuse are not well understood. The present study examined the effects of intragastric (i.g.) ethanol (EtOH) administration in monkeys responding under a schedule of cocaine reinforcement in which extensive drug seeking was maintained by conditioned stimuli. Four adult male cynomolgus monkeys (Macaca fascicularis) were trained to respond under a second-order fixed-interval (FI) 600s (fixed-ratio (FR) 30:S) schedule of cocaine (0.003-0.56mg/kg/injection) presentation. Sessions ended after 5 injections or 90min had elapsed. Different EtOH doses (0.5-2.0g/kg, i.g.) were administered 30min before the session, typically on Tuesdays and Fridays. Blood ethanol concentrations (BECs) were also assessed. Pattern of FI responding was assessed by determining quarter-life (QL) values. Cocaine self-administration was characterized as an inverted U-shaped function of dose; QL values increased monotonically with dose. EtOH pretreatments dose-dependently decreased self-administration at several cocaine doses in 3 of 4 monkeys. In one animal, EtOH increased low-dose cocaine-maintained responding. For all monkeys, QL values were increased by EtOH when low- and high-cocaine doses were self-administered, suggesting additive effects of EtOH and cocaine. Furthermore, BECs were not altered following cocaine self-administration. The reductions in cocaine self-administration and the increases in QL values following EtOH, suggest that EtOH was enhancing cocaine-related conditioned reinforcement. A better understanding of the behavioral mechanisms that mediate the co-abuse of alcohol and cocaine will lead to improved treatments for both drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Large-scale transcriptome sequencing and gene analyses in the crab-eating macaque (Macaca fascicularis) for biomedical research

PubMed Central

2012-01-01

Background As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use. Results Here, we sequenced the transcriptome of 16 tissues originated from two individuals of crab-eating macaque (male and female), and identified genes to resolve the main obstacles for understanding the biological response of the crab-eating macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS FLX sequencing method. Approximately 86% of human genes were represented among the genes sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed. Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally, investigation of TE exonization events and evolutionary analysis were conducted, revealing interesting phenomena of human-specific amplified trends in TE exonization events. Conclusions This report represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and could contribute to its utility for biomedical research and basic biology. PMID:22554259

Cycloartane triterpenes from marine green alga Cladophora fascicularis

NASA Astrophysics Data System (ADS)

Huang, Xinping; Zhu, Xiaobin; Deng, Liping; Deng, Zhiwei; Lin, Wenhan

2006-12-01

Six cycloartanes were isolated from ethanol extract of marine green alga Cladophora fascicularis by column chromatography. Procedure of isolation and description of these compounds are given in this paper. The structures were elucidated as (1). 24-hydroperoxycycloart-25- en-3β-ol; (2). cycloart-25-en-3β 24-diol; (3). 25-hydroperoxycycloart-23-en-3β-ol; (4). cycloart-23-en-3β, 25-diol; (5). cycloart-23, 25-dien-3β-ol; and (6). cycloart-24-en-3β-ol by spectroscopic (MS, ID and 2D NMR) data analysis. Cycloartane derivatives are widely distributed in terrestrial plants, but only few were obtained in the alga. All these compounds that have been isolated from terrestrial plants, were found in the marine alga for the first time.

Type studies of corticioid Hymenomycetes (Basidiomycota) with aculei - Part II

Treesearch

Karen K. Nakasone

2012-01-01

Type specimens of fifteen, resupinate, crustose basidiomycetes with aculei described by various authors were examined. Nine taxa are later synonyms: Hydnum albiceps Berk. & Rav. (= Phlebia fascicularis), Hydnum chrysodon Berk. & M.A. Curtis (= Hydnophlebia chrysorhiza), Hydnum...

Characterization of cement float buoyancy in the stalked barnacle Dosima fascicularis (Crustacea, Cirripedia).

PubMed

Zheden, Vanessa; Kovalev, Alexander; Gorb, Stanislav N; Klepal, Waltraud

2015-02-06

Dosima fascicularis is the only barnacle which can drift autonomously at the water surface with a foam-like cement float. The cement secreted by the animal contains numerous gas-filled cells of different size. When several individuals share one float, their size and not their number is crucial for the production of both volume and mass of the float. The gas content within the cells of the foam gives positive static buoyancy to the whole float. The volume of the float, the gas volume and the positive static buoyancy are positively correlated. The density of the cement float without gas is greater than that of seawater. This study shows that the secreted cement consists of more than 90% water and the gas volume is on average 18.5%. Our experiments demonstrate that the intact foam-like cement float is sealed to the surrounding water.

Characterization of cement float buoyancy in the stalked barnacle Dosima fascicularis (Crustacea, Cirripedia)

PubMed Central

Zheden, Vanessa; Kovalev, Alexander; Gorb, Stanislav N.; Klepal, Waltraud

2015-01-01

Dosima fascicularis is the only barnacle which can drift autonomously at the water surface with a foam-like cement float. The cement secreted by the animal contains numerous gas-filled cells of different size. When several individuals share one float, their size and not their number is crucial for the production of both volume and mass of the float. The gas content within the cells of the foam gives positive static buoyancy to the whole float. The volume of the float, the gas volume and the positive static buoyancy are positively correlated. The density of the cement float without gas is greater than that of seawater. This study shows that the secreted cement consists of more than 90% water and the gas volume is on average 18.5%. Our experiments demonstrate that the intact foam-like cement float is sealed to the surrounding water. PMID:25657839

Sorption and desorption of lead (II) from wastewater by green algae Cladophora fascicularis.

PubMed

Deng, Liping; Su, Yingying; Su, Hua; Wang, Xinting; Zhu, Xiaobin

2007-05-08

Biosorption is an effective method to remove heavy metals from wastewater. In this work, adsorption features of Cladophora fascicularis were investigated as a function of time, initial pH, initial Pb(II) concentrations, temperature and co-existing ions. Kinetics and equilibria were obtained from batch experiments. The biosorption kinetics followed the pseudo-second order model. Adsorption equilibria were well described by the Langmuir and Freundlich isotherm models. The maximum adsorption capacity was 198.5 mg/g at 298K and pH 5.0. The adsorption processes were endothermic and the biosorption heat was 29.6 kJ/mol. Desorption experiments indicated that 0.01 mol/L Na(2)EDTA was an efficient desorbent for the recovery of Pb(II) from biomass. IR spectrum analysis suggested amido or hydroxy, CO and C-O could combine intensively with Pb(II).

Study of the gastrointestinal parasitic fauna of captive non-human primates (Macaca fascicularis).

PubMed

Zanzani, Sergio Aurelio; Gazzonis, Alessia Libera; Epis, Sara; Manfredi, Maria Teresa

2016-01-01

The aim of this study was to examine helminths and protozoans in cynomolgus macaques (Macaca fascicularis) imported from registered breeding facilities in China and their relation to health risks for non-human primate handlers in biomedical research centers and in breeding facilities. Fresh fecal samples were collected from a total of 443 M. fascicularis and analyzed by copromicroscopical analysis, immunoenzymatic, or molecular assays. As to helminths, whose eggs were shed in 2.03% of the samples, Trichuris and Oesophagostomum were the only two taxa found, with low prevalence and low eggs per gram (EPG) values. Protozoans were more frequently detected (87.40%), with Entamoeba coli (85.19%) and Endolimax nana (79.26%) as the most prevalent species shed. Other parasites found by fecal smear examination were uninucleated-cyst-producing Entamoebas (78.52%), Iodamoeba bütschlii (42.96%), and Chilomastix mesnili (24.44%), while cysts of Balantidium coli (22.2%) were only observed by sedimentation. No coproantigens of Giardia duodenalis, Cryptosporidium spp., and Entamoeba histolytica complex were detected. Blastocystis sp. infection was noticed in 87.63% of macaques by PCR. These cynomolgus monkeys were infected with many subtypes (ST1, ST2, ST3, ST5, and ST7), where the predominant Blastocystis sp. subtypes were ST2 (77.5%), followed by ST1 (63.5%). Data collected confirmed the presence of potentially zoonotic parasites and a high parasite diversity, suggesting the need for appropriate and sensitive techniques to adequately control them and related health risks for handlers of non-human primates in biomedical research centers and in breeding facilities.

Impacts of sediments on coral energetics: partitioning the effects of turbidity and settling particles.

PubMed

Junjie, Reef K; Browne, Nicola K; Erftemeijer, Paul L A; Todd, Peter A

2014-01-01

Sediment loads have long been known to be deleterious to corals, but the effects of turbidity and settling particles have not previously been partitioned. This study provides a novel approach using inert silicon carbide powder to partition and quantify the mechanical effects of sediment settling versus reduced light under a chronically high sedimentary regime on two turbid water corals commonly found in Singapore (Galaxea fascicularis and Goniopora somaliensis). Coral fragments were evenly distributed among three treatments: an open control (30% ambient PAR), a shaded control (15% ambient PAR) and sediment treatment (15% ambient PAR; 26.4 mg cm(-2) day(-1)). The rate of photosynthesis and respiration, and the dark-adapted quantum yield were measured once a week for four weeks. By week four, the photosynthesis to respiration ratio (P/R ratio) and the photosynthetic yield (Fv/Fm) had fallen by 14% and 3-17% respectively in the shaded control, contrasting with corals exposed to sediments whose P/R ratio and yield had declined by 21% and 18-34% respectively. The differences in rates between the shaded control and the sediment treatment were attributed to the mechanical effects of sediment deposition. The physiological response to sediment stress differed between species with G. fascicularis experiencing a greater decline in the net photosynthetic yield (13%) than G. somaliensis (9.5%), but a smaller increase in the respiration rates (G. fascicularis = 9.9%, G. somaliensis  = 14.2%). These different physiological responses were attributed, in part, to coral morphology and highlighted key physiological processes that drive species distribution along high to low turbidity and depositional gradients.

Evaluation of Serum Lipid, Thyroid, and Hepatic Clinical Chemistries in Association With Serum Perfluorooctanesulfonate (PFOS) in Cynomolgus Monkeys After Oral Dosing With Potassium PFOS

PubMed Central

Allen, Bruce C.; Andres, Kara L.; Ehresman, David J.; Falvo, Ria; Provencher, Anne; Olsen, Geary W.; Butenhoff, John L.

2017-01-01

Abstract An oral dose study with perfluorooctanesulfonate (PFOS) was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fascicularis). In this study, control group (n = 6/sex) was sham-dosed with vehicle (0.5% Tween 20 and 5% ethanol in water), low-dose group (n = 6/sex) received 1 single K+PFOS dose (9 mg/kg), and high-dose group (n = 4–6/sex) received 3 separate K+ PFOS doses (11–17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior to, during, and after K+PFOS administration for up to 1 year and they were analyzed for PFOS concentrations and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 μg/ml. When compared with time-matched controls, administration of K+PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the high-density lipoprotein fraction), although not toxicologically significant, was observed. The corresponding lower-bound fifth percentile benchmark concentrations (BMCL1sd) were 74 and 76 μg/ml for male and female monkeys, respectively. Compared to the 2013–2014 geometric mean serum PFOS level of 4.99 ng/ml (0.00499 μg/ml) in US general population reported by CDC NHANES, this represents 4 orders of magnitude for margin of exposure. PMID:28115654

Selection and Investigation of a Primate Model of Spontaneous Degenerative Knee Osteoarthritis, the Cynomolgus Monkey (Macaca Fascicularis).

PubMed

Liu, Gang; Zhang, Lei; Zhou, Xin; Zhang, Bao L; Guo, Guang X; Xu, Ping; Wang, Guo Y; Fu, Shi J

2018-07-01

BACKGROUND The aim of this study was to identify a primate model of degenerative knee osteoarthritis (KOA) that may be more relevant for research studies on degenerative KOA in humans. MATERIAL AND METHODS Sixteen specific-pathogen-free (SPF) male cynomolgus monkeys (Macaca fascicularis) were divided into group A (n=8), an old group (22.0-25.3 years of age), and group B (n=8), a young group (3.0-5.2 years of age). For each primate, the behavior was observed, knee circumference was measured, knee joint X-rays were performed, and peripheral blood white blood cell (WBC) counts were measured, and the Kellgren and Lawrence (K-L) system was used for the classification of osteoarthritis. An enzyme-linked immunoassay (ELISA) was performed on knee joint fluid to measure levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)13. Changes in articular cartilage were evaluated using the Brittberg score and the Mankin histopathology grading score, respectively. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were used to measure the expression of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and the findings in the two groups of primates were compared. RESULTS Seven old aged primates in group A were compared with group B, and showed significant differences in WBC count, synovial fluid IL-1β, TGF-β1, and MMP13 levels, expression levels of the NOTCH3, JAG1, and ACAN genes in knee cartilage specimens, and in the Brittberg and Mankin scores (all, P<0.05). CONCLUSIONS Cynomolgus monkeys (Macaca fascicularis) might be a model for age-related degenerative KOA.

Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.

PubMed

Grégoire, Laurent; Samadi, Pershia; Graham, Julie; Bédard, Paul J; Bartoszyk, Gerd D; Di Paolo, Thérèse

2009-07-01

Dyskinesia is an important complication of treatment in Parkinson's disease (PD). Sarizotan, a 5-HT(1A) agonist with high affinity for D3 and D4 receptors was investigated on L-Dopa-induced dyskinesia (LID) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. Five MPTP female cynomolgus monkeys (Macaca fascicularis) with a moderate to severe parkinsonian syndrome and LID were used. Sarizotan 0.2, 1, and 2 mg/kg administered alone did not worsen parkinsonian symptoms; there were no effect on locomotor counts or on normal behavior of the monkeys. Sarizotan 0.2, 1, and 2 mg/kg administered 30 min before a fixed dose of L-Dopa (25-30 mg/kg s.c.) + benserazide (50 mg) did not affect the antiparkinsonian response to L-Dopa. However, mean dyskinetic scores were significantly reduced with sarizotan 1 and 2 mg/kg but not at 0.2 mg/kg. Higher doses of sarizotan (4 and 8 mg/kg, administered immediately before L-Dopa) reduced L-Dopa-induced locomotor response in all monkeys. A pharmacokinetic investigation in these monkeys showed a dose-dependent increase in mean plasma sarizotan concentrations with similar mean plasma concentrations for sarizotan 1 mg/kg alone or with L-Dopa, indicating a lack of sarizotan/L-Dopa interaction. The time course of plasma sarizotan concentrations was associated with time of maximal reduction of dyskinesias. When administered daily for two weeks in combination with L-Dopa in the same MPTP monkeys, sarizotan 1 mg/kg had a sustained antidyskinetic effect while maintaining the antiparkinsonian and locomotor effect of L-Dopa. This detailed sarizotan investigation in MPTP monkeys supports the antidyskinetic activity of this drug and for 5-HT(1A) agonists.

Pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (Macaca fascicularis).

PubMed

Kuiken, Thijs; Buijs, Pascal; van Run, Peter; van Amerongen, Geert; Koopmans, Marion; van den Hoogen, Bernadette

2017-11-21

Although avian paramyxovirus type 1 is known to cause mild transient conjunctivitis in human beings, there are two recent reports of fatal respiratory disease in immunocompromised human patients infected with the pigeon lineage of the virus (PPMV-1). In order to evaluate the potential of PPMV-1 to cause respiratory tract disease, we inoculated a PPMV-1 isolate (hPPMV-1/Netherlands/579/2003) from an immunocompromised human patient into three healthy cynomolgus macaques (Macaca fascicularis) and examined them by clinical, virological, and pathological assays. In all three macaques, PPMV-1 replication was restricted to the respiratory tract and caused pulmonary consolidation affecting up to 30% of the lung surface. Both alveolar and bronchiolar epithelial cells expressed viral antigen, which co-localized with areas of diffuse alveolar damage. The results of this study demonstrate that PPMV-1 is a primary respiratory pathogen in cynomolgus macaques, and support the conclusion that PPMV-1 may cause fatal respiratory disease in immunocompromised human patients.

A crypto-lymphatic unit at the uvula of the monkey Macaca fascicularis. A light- and electron-microscopic study.

PubMed

Nair, P N

1983-01-01

A crypto-lymphatic unit was observed at the left lateral aspect of the uvula of a mature female monkey, Macaca fascicularis. A light- and transmission electron-microscopic investigation revealed that the lumen of the crypt was filled with bacteria, desquamated epithelial cells, lymphocytes and neutrophils. The non-keratinized stratified squamous epithelium of the crypt was fragmented and showed heavy mononuclear cell infiltration and surface discontinuities, exposing lymphoid cells to foreign material. The lymphatic parenchyma consisted of organized lymphatic tissue including germinal centres. The resident cell population included lymphocytes of varying size, blastforming B- and T-lymphocytes and two types of reticular cells resembling the fibroblastic reticulum cell and the follicular dendritic cell, respectively. Occasionally granulocytes were encountered. At its base and laterally the crypto-lymphatic unit was ensheathed by a thin connective tissue capsule. Three other monkeys of the same species failed to reveal similar structures at the same site.

Biosorption of copper(II) from aqueous solutions by green alga Cladophora fascicularis.

PubMed

Deng, Liping; Zhu, Xiaobin; Wang, Xinting; Su, Yingying; Su, Hua

2007-08-01

Biosorption is an effective means of removal of heavy metals from wastewater. In this work the biosorption behavior of Cladophora fascicularis was investigated as a function of pH, amount of biosorbent, initial Cu2+ concentration, temperature, and co-existing ions. Adsorption equilibria were well described by Langmuir isotherm models. The enthalpy change for the biosorption process was found to be 6.86 kJ mol(-1) by use of the Langmuir constant b. The biosorption process was found to be rapid in the first 30 min. The presence of co-existing cations such as Na+, K+, Mg2+, and Ca2+ and anions such as chloride, nitrate, sulfate, and acetate did not significantly affect uptake of Cu2+ whereas EDTA substantially affected adsorption of the metal. When experiments were performed with different desorbents the results indicated that EDTA was an efficient desorbent for the recovery of Cu2+ from biomass. IR spectral analysis suggested amido or hydroxy, C=O, and C-O could combine strongly with Cu2+.

Primate-to-Human Retroviral Transmission in Asia

PubMed Central

Engel, Gregory A.; Schillaci, Michael A.; Rompis, Aida; Putra, Artha; Suaryana, Komang Gde; Fuentes, Agustin; Beer, Brigitte; Hicks, Sarah; White, Robert; Wilson, Brenda; Allan, Jonathan S.

2005-01-01

We describe the first reported transmission to a human of simian foamy virus (SFV) from a free-ranging population of nonhuman primates in Asia. The transmission of an exogenous retrovirus, SFV, from macaques (Macaca fascicularis) to a human at a monkey temple in Bali, Indonesia, was investigated with molecular and serologic techniques. Antibodies to SFV were detected by Western blotting of serum from 1 of 82 humans tested. SFV DNA was detected by nested polymerase chain reaction (PCR) from the blood of the same person. Cloning and sequencing of PCR products confirmed the virus's close phylogenetic relationship to SFV isolated from macaques at the same temple. This study raises concerns that persons who work at or live around monkey temples are at risk for infection with SFV. PMID:16022776

A multi-atlas based method for automated anatomical Macaca fascicularis brain MRI segmentation and PET kinetic extraction.

PubMed

Ballanger, Bénédicte; Tremblay, Léon; Sgambato-Faure, Véronique; Beaudoin-Gobert, Maude; Lavenne, Franck; Le Bars, Didier; Costes, Nicolas

2013-08-15

MRI templates and digital atlases are needed for automated and reproducible quantitative analysis of non-human primate PET studies. Segmenting brain images via multiple atlases outperforms single-atlas labelling in humans. We present a set of atlases manually delineated on brain MRI scans of the monkey Macaca fascicularis. We use this multi-atlas dataset to evaluate two automated methods in terms of accuracy, robustness and reliability in segmenting brain structures on MRI and extracting regional PET measures. Twelve individual Macaca fascicularis high-resolution 3DT1 MR images were acquired. Four individual atlases were created by manually drawing 42 anatomical structures, including cortical and sub-cortical structures, white matter regions, and ventricles. To create the MRI template, we first chose one MRI to define a reference space, and then performed a two-step iterative procedure: affine registration of individual MRIs to the reference MRI, followed by averaging of the twelve resampled MRIs. Automated segmentation in native space was obtained in two ways: 1) Maximum probability atlases were created by decision fusion of two to four individual atlases in the reference space, and transformation back into the individual native space (MAXPROB)(.) 2) One to four individual atlases were registered directly to the individual native space, and combined by decision fusion (PROPAG). Accuracy was evaluated by computing the Dice similarity index and the volume difference. The robustness and reproducibility of PET regional measurements obtained via automated segmentation was evaluated on four co-registered MRI/PET datasets, which included test-retest data. Dice indices were always over 0.7 and reached maximal values of 0.9 for PROPAG with all four individual atlases. There was no significant mean volume bias. The standard deviation of the bias decreased significantly when increasing the number of individual atlases. MAXPROB performed better when increasing the number of atlases used. When all four atlases were used for the MAXPROB creation, the accuracy of morphometric segmentation approached that of the PROPAG method. PET measures extracted either via automatic methods or via the manually defined regions were strongly correlated, with no significant regional differences between methods. Intra-class correlation coefficients for test-retest data were over 0.87. Compared to single atlas extractions, multi-atlas methods improve the accuracy of region definition. They also perform comparably to manually defined regions for PET quantification. Multiple atlases of Macaca fascicularis brains are now available and allow reproducible and simplified analyses. Copyright © 2013 Elsevier Inc. All rights reserved.

The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey.

PubMed

Wang, Yiwen; Danilova, Vicktoria; Cragin, Tiffany; Roberts, Thomas W; Koposov, Alexey; Hellekant, Göran

2009-02-18

Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers. We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers. In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non-S fibers originates from other kinds of receptors. The absence of the effect of lactisole on the faint responses in some S fibers to other stimuli as well as the responses to sweet and non-sweet stimuli in non-S fibers suggest that these responses originate from other taste receptors.

Macaque Monkeys Discriminate Pitch Relationships

ERIC Educational Resources Information Center

Brosch, Michael; Selezneva, Elena; Bucks, Cornelia; Scheich, Henning

2004-01-01

This study demonstrates that non-human primates can categorize the direction of the pitch change of tones in a sequence. Two "Macaca fascicularis" were trained in a positive-reinforcement behavioral paradigm in which they listened to sequences of a variable number of different acoustic items. The training of discriminating pitch direction was…

Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive.

PubMed

O'Rand, Michael G; Hamil, Katherine G; Adevai, Tiffany; Zelinski, Mary

2018-01-01

Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75-80 mg/kg) followed by a recovery period and a subsequent high dose (125-130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.

Use of Operant Performance to Guide and Evaluate Medical Treatment in an Adult Male Cynomolgus Macaque (Macaca fascicularis)

DTIC Science & Technology

2011-11-01

verbal behavior (for example, reading, writing, speaking) and refined motor performances (for example, driving a car, brushing one’s teeth , playing a...food daily (no. 8714 Teklad 15% Monkey Diet , Harlan Laboratories, Indianapolis, IN, and fresh fruit and vegetables) to maintain body weight at

Telomere length of the colonial coral Galaxea fascicularis at different developmental stages

NASA Astrophysics Data System (ADS)

Tsuta, H.; Hidaka, M.

2013-06-01

The ability to estimate coral age using soft tissue would be useful for population biology or aging studies on corals. In this study, we investigated whether telomere length can be used to estimate coral age. We applied single telomere length analysis to a colonial coral, Galaxea fascicularis, and estimated telomere lengths of specific coral chromosomes at different developmental stages. If the telomere shortened at each cell division, the telomere length of the coral would be longest in sperm and shortest in adult colonies. However, the mean telomere length of sperm, planula larvae, and polyps was approximately 4 kb, with no significant differences among the developmental stages. The telomerase restriction fragment (TRF) analysis also showed no significant difference in the mean TRF length among the developmental stages. Our results suggested that telomere length is maintained during developmental stages and that estimating the age of colonial coral based on telomere length may not be possible. However, our findings can be used to examine avoidance of aging and rejuvenation during regeneration and asexual reproduction in colonial corals.

Thoracic Radiography as a Refinement Methodology for the Study of H1N1 Influenza in Cynomologus Macaques (Macaca fascicularis)

PubMed Central

Brining, Douglas L; Mattoon, John S; Kercher, Lisa; LaCasse, Rachael A; Safronetz, David; Feldmann, Heinz; Parnell, Michael J

2010-01-01

Recent advances in the technology associated with digital radiography have created new opportunities for biomedical research applications. Here we evaluated the use of thoracic radiography as a noninvasive refinement methodology for the cynomologus macaque (Macaca fascicularis) model of H1N1 infection. Thoracic radiographic evaluations of macaques infected with any of 3 strains of emerging H1N1 swine-associated influenza virus isolated during the recent pandemic were compared with those of macaques infected with the currently circulating Kawasaki strain of H1N1 influenza. Ventrodorsal, right, and left lateral thoracic radiographs were obtained at days 0, 1, 6, 8, 11, and 14 after infection. A board-certified veterinary radiologist who was blinded to the study design evaluated the images. Numeric scores of extent and severity of lung involvement assigned to each radiograph were compared and demonstrated a significant and substantial difference among groups. The radiographic evaluation allowed for noninvasive assessment of lung involvement, disease onset, progression, and resolution of radiographic changes associated with H1N1 influenza infection. PMID:21262125

Exploring of Primate Models of Tick-Borne Flaviviruses Infection for Evaluation of Vaccines and Drugs Efficacy

PubMed Central

Pripuzova, Natalia S.; Gmyl, Larissa V.; Romanova, Lidiya Iu.; Tereshkina, Natalia V.; Rogova, Yulia V.; Terekhina, Liubov L.; Kozlovskaya, Liubov I.; Vorovitch, Mikhail F.; Grishina, Karina G.; Timofeev, Andrey V.; Karganova, Galina G.

2013-01-01

Tick-borne encephalitis virus (TBEV) is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV) in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8–16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to TBEV than C. aethiops. PMID:23585873

Climatic effects on the nasal complex: a CT imaging, comparative anatomical, and morphometric investigation of Macaca mulatta and Macaca fascicularis.

PubMed

Márquez, Samuel; Laitman, Jeffrey T

2008-11-01

Previous studies exploring the effects of climate on the nasal region have largely focused on external craniofacial linear parameters, using dry crania of modern human populations. This investigation augments traditional craniofacial morphometrics with internal linear and volumetric measures of the anatomic units comprising the nasal complex (i.e., internal nasal cavity depth, maxillary sinus volumes). The study focuses on macaques (i.e., Macaca mulatta and Macaca fascicularis) living at high and low altitudes, rather than on humans, since the short residency of migratory human populations may preclude using them as reliable models to test the long-term relationship of climate to nasal morphology. It is hypothesized that there will be significant differences in nasal complex morphology among macaques inhabiting different climates. This study integrated three different approaches: CT imaging, comparative anatomy, and morphometrics-in an effort to better understand the morphological structure and adaptive nature of the nasal complex. Results showed statistically significant differences when subsets of splanchnocranial and neurocranial variables were regressed against total maxillary sinus volume for particular taxa. For example, basion-hormion was significant for M. fascicularis, whereas choanal dimensions were significant only for M. mulatta. Both taxa revealed strong correlation between sinus volume and prosthion to staphylion distance, which essentially represents the length of the nasal cavity floor-and is by extension an indicator of the air conditioning capacity of the nasal region. These results clearly show that climatic effects play a major role in shaping the anatomy of the nasal complex in closely related species. The major influence upon these differing structures appears to be related to respiratory-related adaptations subserving differing climatic factors. In addition, the interdependence of the paranasal sinuses with other parts of the complex strongly indicates a functional role for them in nasal complex/upper respiratory functions. Copyright 2008 Wiley-Liss, Inc.

Pre- and Post-harvest Influences on Seed Dormancy Status of an Australian Goodeniaceae species, Goodenia fascicularis

PubMed Central

Hoyle, Gemma L.; Steadman, Kathryn J.; Daws, Matthew I.; Adkins, Steve W.

2008-01-01

Background and Aims The period during which seeds develop on the parent plant has been found to affect many seed characteristics, including dormancy, through interactions with the environment. Goodenia fascicularis (Goodeniaceae) seeds were used to investigate whether seeds of an Australian native forb, harvested from different environments and produced at different stages of the reproductive period, differ in dormancy status. Methods During the reproductive phase, plants were grown ex situ in warm (39/21 °C) or cool (26/13 °C) conditions, with adequate or limited water availability. The physiological dormancy of resulting seeds was measured in terms of the germination response to warm stratification (34/20 °C, 100 % RH, darkness). Key Results Plants in the cool environment were tall and had high above-ground biomass, yet yielded fewer seeds over a shorter, later harvest period when compared with plants in the warm environment. Seeds from the cool environment also had higher viability and greater mass, despite a significant proportion (7 % from the cool-wet environment) containing no obvious embryo. In the warm environment, the reproductive phase was accelerated and plants produced more seeds despite being shorter and having lower above-ground biomass than those in the cool environment. Ten weeks of warm stratification alleviated physiological dormancy in seeds from all treatments resulting in 80–100 % germination. Seeds that developed at warm temperatures were less dormant (i.e. germination percentages were higher) than seeds from the cool environment. Water availability had less effect on plant and seed traits than air temperature, although plants with reduced soil moisture were shorter, had lower biomass and produced fewer, less dormant seeds than plants watered regularly. Conclusions Goodenia fascicularis seeds are likely to exhibit physiological dormancy regardless of the maternal environment. However, seeds collected from warm, dry environments are likely to be more responsive to warm stratification than seeds from cooler, wetter environments. PMID:18430743

Tamoxifen-DNA adduct formation in monkey and human reproductive organs.

PubMed

Hernandez-Ramon, Elena E; Sandoval, Nicole A; John, Kaarthik; Cline, J Mark; Wood, Charles E; Woodward, Ruth A; Poirier, Miriam C

2014-05-01

The estrogen analog tamoxifen (TAM), used for adjuvant therapy of breast cancer, induces endometrial and uterine tumors in breast cancer patients. Proliferation stimulus of the uterine endometrium is likely involved in tumor induction, but genotoxicity may also play a role. Formation of TAM-DNA adducts in human tissues has been reported but remains controversial. To address this issue, we examined TAM-DNA adducts in uteri from two species of monkeys, Erythrocebus patas (patas) and Macaca fascicularis (macaque), and in human endometrium and myometrium. Monkeys were given 3-4 months of chronic TAM dosing scaled to be equivalent to the daily human dose. In the uteri, livers and brains from the patas (n = 3), and endometrium from the macaques (n = 4), TAM-DNA adducts were measurable by TAM-DNA chemiluminescence immunoassay. Average TAM-DNA adduct values for the patas uteri (23 adducts/10(8) nucleotides) were similar to those found in endometrium of the macaques (19 adducts/10(8) nucleotides). Endometrium of macaques exposed to both TAM and low-dose estradiol (n = 5) averaged 34 adducts/10(8) nucleotides. To examine TAM-DNA persistence in the patas, females (n = 3) were exposed to TAM for 3 months and to no drug for an additional month, resulting in low or non-detectable TAM-DNA in livers and uteri. Human endometrial and myometrial samples from women receiving (n = 8) and not receiving (n = 8) TAM therapy were also evaluated. Women receiving TAM therapy averaged 10.3 TAM-DNA adducts/10(8) nucleotides, whereas unexposed women showed no detectable TAM-DNA. The data indicate that genotoxicity, in addition to estrogen agonist effects, may contribute to TAM-induced human endometrial cancer.

Absorbed radiation dosimetry of the D3-specific PET radioligand [18F]FluorTriopride estimated using rodent and nonhuman primate.

PubMed

Laforest, Richard; Karimi, Morvarid; Moerlein, Stephen M; Xu, Jinbin; Flores, Hubert P; Bognar, Christopher; Li, Aixiao; Mach, Robert H; Perlmutter, Joel S; Tu, Zhude

2016-01-01

[ 18 F]FluorTriopride ([ 18 F]FTP) is a dopamine D 3 -receptor preferring radioligand with potential for investigation of neuropsychiatric disorders including Parkinson disease, dystonia and schizophrenia. Here we estimate human radiation dosimetry for [ 18 F]FTP based on the ex-vivo biodistribution in rodents and in vivo distribution in nonhuman primates. Biodistribution data were generated using male and female Sprague-Dawley rats injected with ~370 KBq of [ 18 F]FTP and euthanized at 5, 30, 60, 120, and 240 min. Organs of interest were dissected, weighed and assayed for radioactivity content. PET imaging studies were performed in two male and one female macaque fascicularis administered 143-190 MBq of [ 18 F]FTP and scanned whole-body in sequential sections. Organ residence times were calculated based on organ time activity curves (TAC) created from regions of Interest. OLINDA/EXM 1.1 was used to estimate human radiation dosimetry based on scaled organ residence times. In the rodent, the highest absorbed radiation dose was the upper large intestines (0.32-0.49 mGy/MBq), with an effective dose of 0.07 mSv/MBq in males and 0.1 mSv/MBq in females. For the nonhuman primate, however, the gallbladder wall was the critical organ (1.81 mGy/MBq), and the effective dose was 0.02 mSv/MBq. The species discrepancy in dosimetry estimates for [ 18 F]FTP based on rat and primate data can be attributed to the slower transit of tracer through the hepatobiliary track of the primate compared to the rat, which lacks a gallbladder. Out findings demonstrate that the nonhuman primate model is more appropriate model for estimating human absorbed radiation dosimetry when hepatobiliary excretion plays a major role in radiotracer elimination.

Variation in hair δ13C and δ15N values in long-tailed macaques (Macaca fascicularis) from Singapore

USGS Publications Warehouse

Schillaci, Michael A.; Castellini, J. Margaret; Stricker, Craig A.; Jones-Engel, Lisa; Lee, Benjamin P.Y.-H.

2014-01-01

Much of the primatology literature on stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) has focused on African and New World species, with comparatively little research published on Asian primates. Here we present hair δ13C and δ15N isotope values for a sample of 33 long-tailed macaques from Singapore. We evaluate the suggestion by a previous researcher that forest degradation and biodiversity loss in Singapore have led to a decline in macaque trophic level. The results of our analysis indicated significant spatial variability in δ13C but not δ15N. The range of variation in δ13C was consistent with a diet based on C3 resources, with one group exhibiting low values consistent with a closed canopy environment. Relative to other macaque species from Europe and Asia, the macaques from Singapore exhibited a low mean δ13C value but mid-range mean δ15N value. Previous research suggesting a decline in macaque trophic level is not supported by the results of our study.

Equilibrium Performance Changes Produced by Atropine in M. mulatta and M. fascicularis.

DTIC Science & Technology

1981-09-01

the behavior of one animal within each group was more severely disrupted than the others. A Student -Newman-Keuls Multiple Comparison Test (31) on the...Med 45(11):1291- 1297 (1974). 7. I)ix, M. R. Treatment of vertigo. Physiotherapy 60(12):380-384 (1974). 8. Fregly, A. R., M. J. Smith, C. D. Wood, and

Assessment of early placental development in the cynomolgus monkey (Macaca fascicularis) using colour and pulsed wave Doppler sonography.

PubMed

Nimrod, C; Simpson, N; Hafner, T; de Vermette, R; Fournier, J; Coady, L; Baccanale, C

1996-04-01

Colour flow mapping and pulsed wave Doppler were used to assess the process of placental growth and development in the cynomolgus monkey from 32 to 71 days gestational age. Fetal and maternal vessels were reliably visualised and insonated. Accurate longitudinal non-invasive assessment of placentation is possible using this technique.

Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

2011-01-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis).

PubMed

Fong, Derek L; Murnane, Robert D; Hotchkiss, Charlotte E; Green, Damian J; Hukkanen, Renee R

2011-02-01

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.

Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis).

PubMed

Laffins, Michael M; Mellal, Nacera; Almlie, Cynthia L; Regalia, Douglas E

2017-01-01

Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations. Infrared measurements were taken 5 cm from the chest and inguinal areas. We evaluated 10 (9 functional devices) sedated cynomolgus macaques (5 male, 5 female) implanted with telemetry units in a muscular pouch between the internal and external abdominal oblique muscles. We determined that the mean body temperature acquired by using telemetry did not differ from either the mean of inguinal and chest infrared measurements but did differ from the mean of temperature obtained rectally. In addition, the mean rectal temperature differed from the mean of the inguinal reading but not the mean of the chest temperature. The results confirm our hypothesis that the infrared thermometer can be used to replace standard rectal thermometry.

Urban primate ranging patterns: GPS-collar deployments for Macaca fascicularis and M. sylvanus.

PubMed

Klegarth, Amy R; Hollocher, Hope; Jones-Engel, Lisa; Shaw, Eric; Lee, Benjamin P Y-H; Feeney, Tessa; Holmes, Damian; Laguea, Dale; Fuentes, Agustín

2017-05-01

The global increase in urbanization is leading to heavier interface between humans and wildlife. Within these anthropogenic landscapes, little is known about ranging patterns, particularly with regard to urban primates. Here we present the results of the first long-term deployment of multiple GPS collars on two species of macaques to investigate the impacts of urbanization on urban primate ranging patterns in Singapore and Gibraltar. Collars data acquisition were excellent with respect to the amount, quality, and accuracy of data collected; however, remote connectivity and drop-off functionality was poor across all deployments. Analyses highlighted high variability in ranging patterns between individuals within each species that aligned with access to human food resources and patterns of tourism. Individuals from troops with less access to human food had much larger home, core, and day ranges relative to those with regular provisioning or raiding opportunities. Almost no temporal range overlap was observed between any focal individuals at either site and spatial overlap was low for all but two troops at each site. We found no relationship between anthropogenic schedules and changes in ranging patterns. Significant seasonal variation existed for daily path length and day range size for both the Singapore long-tailed and the Gibraltar Barbary macaques, with long-tailed macaques increasing their range during the equatorial monsoon season and Barbary macaques increasing their range during drier, summer months. This study highlights how the behavioral plasticity found within the genus Macaca is reflected in ranging pattern variability within urban environments. © 2017 Wiley Periodicals, Inc.

Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

PubMed

Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

2012-12-01

In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparative community-level associations of helminth infections and microparasite shedding in wild long-tailed macaques in Bali, Indonesia.

PubMed

Wilcox, Justin J S; Lane-Degraaf, Kelly E; Fuentes, Agustin; Hollocher, Hope

2015-03-01

Helminthes have the capacity to modulate host immunity, leading to positive interactions with coinfecting microparasites. This phenomenon has been primarily studied during coinfections with a narrow range of geo-helminthes and intracellular microparasites in human populations or under laboratory conditions. Far less is known regarding differences in coinfection dynamics between helminth types, the range of microparasites that might be affected or the overall community-level effects of helminth infections on microparasites in wild systems. Here, we analysed the presence/absence and abundance patterns of enteric parasites in long-tailed macaques (Macaca fascicularis) on the island of Bali, Indonesia, to assess whether naturally occurring helminth infections were associated with increased shedding of the most common intracellular (Cryptosporidium spp., Isospora spp.) and extracellular (Entamoeba spp., Giardia spp.) microparasites. We also comparatively assessed the statistical correlations of different helminth taxa with microparasite shedding to determine if there were consistent relationships between the specific helminth taxa and microparasites. Helminth infections were associated with increased shedding of both intracellular and extracellular microparasites. Platyhelminthes repeatedly displayed strong positive correlations with several microparasites; while nematodes did not. Our results indicate that helminthes can influence microparasite community shedding dynamics under wild conditions, but that trends may be driven by a narrow range of helminthes.

Performance Correlates of Social Behavior and Organization in Non-Human Primates.

DTIC Science & Technology

1982-04-01

behavior of the two breeding troops of fascicularis revealed the general contributions of affiliative behaviors and of matriarchical groups to the social...effort interacting with the other members of their societies , it might be expected that such interactions, and their consequences, would have pervasive...February, 1976, the second ranking matriarchy in NT-Troop lost its matriarch , Patsy. However, her oldest daughter, Dusty, continued to dominate all of the

Finding the factors of reduced genetic diversity on X chromosomes of Macaca fascicularis: male-driven evolution, demography, and natural selection.

PubMed

Osada, Naoki; Nakagome, Shigeki; Mano, Shuhei; Kameoka, Yosuke; Takahashi, Ichiro; Terao, Keiji

2013-11-01

The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.34 and 0.20 in the Indonesian-Malaysian and Philippine populations, respectively, considerably lower than the null expectation of 0.75. A Philippine population supposed to derive from an ancestral population by founding events showed a significantly lower ratio than the parental population, suggesting a demographic effect for the reduction. Taking sex-specific mutation rate bias and demographic effect into account, expected X/A diversity ratios generated by computer simulations roughly agreed with the observed data in the intergenic regions. In contrast, silent sites in genic regions on X chromosomes showed strong reduction in genetic diversity and the observed X/A diversity ratio in the genic regions cannot be explained by mutation rate bias and demography, indicating that natural selection also reduces the level of polymorphism near genes. Whole-genome analysis of a female cynomolgus monkey also supported the notion of stronger reduction of genetic diversity near genes on the X chromosome.

No costly prosociality among related long-tailed macaques (Macaca fascicularis).

PubMed

Sterck, Elisabeth H M; Olesen, Caroline U; Massen, Jorg J M

2015-08-01

Altruism, benefiting another at a cost to the donor, may be achieved through prosocial behavior. Studies of nonhuman animals typically investigate prosocial behavior with paradigms in which the donor can choose to give a recipient a food item, and the choice does not affect the donor's reward (which is either present or absent). In such tasks, long-tailed macaques (Macaca fascicularis) show prosocial behavior, especially toward kin. Here, we tested captive long-tailed macaques with related recipients in an alternative task, in which the donor had to give up a preferred reward to benefit the recipient; that is, they had to choose a lower valued reward for themselves to provide food to their kin. Overall, the macaques did not provide their kin with food. The task forced the donor to balance its prosocial behavior with its selfish choice for a higher value reward, a balance that turned out to favor selfish motives. Consequently, our study shows that a prosocial tendency is not sufficient to elicit costly prosocial behavior in long-tailed macaques. Subsequently, we feel that tasks in which the donor must choose a lower value reward to benefit another individual may allow the titration of the strength of prosocial behavior, and thus provides interesting possibilities for future comparative studies. (c) 2015 APA, all rights reserved).

The effects of thermal and high-CO2 stresses on the metabolism and surrounding microenvironment of the coral Galaxea fascicularis.

PubMed

Agostini, Sylvain; Fujimura, Hiroyuki; Higuchi, Tomihiko; Yuyama, Ikuko; Casareto, Beatriz E; Suzuki, Yoshimi; Nakano, Yoshikatsu

2013-08-01

The effects of elevated temperature and high pCO2 on the metabolism of Galaxea fascicularis were studied with oxygen and pH microsensors. Photosynthesis and respiration rates were evaluated from the oxygen fluxes from and to the coral polyps. High-temperature alone lowered both photosynthetic and respiration rates. High pCO2 alone did not significantly affect either photosynthesis or respiration rates. Under a combination of high-temperature and high-CO2, the photosynthetic rate increased to values close to those of the controls. The same pH in the diffusion boundary layer was observed under light in both (400 and 750 ppm) CO2 treatments, but decreased significantly in the dark as a result of increased CO2. The ATP contents decreased with increasing temperature. The effects of temperature on the metabolism of corals were stronger than the effects of increased CO2. The effects of acidification were minimal without combined temperature stress. However, acidification combined with higher temperature may affect coral metabolism due to the amplification of diel variations in the microenvironment surrounding the coral and the decrease in ATP contents. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Comparison of Saliva Collection Methods for the Determination of Salivary Cortisol Levels in Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), and African Green Monkeys (Chlorocebus aethiops)

PubMed Central

Rapp-Santos, Kamala J; Altamura, Louis A; Norris, Sarah L; Lugo-Roman, Luis A; Rico, Pedro J; Hofer, Christian C

2017-01-01

The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis) and African green monkeys (Chlorocebus aethiops) at 2 collection time points. Serum and salivary cortisol levels were determined using a competitive quantitative ELISA. In addition, both saliva collection methods were evaluated for volume collected and ease of use. Compared with passive drool, the experimental collection device was more reliable in collecting sufficient volumes of saliva, and the resulting salivary cortisol values demonstrated stronger correlation with serum cortisol concentration in all species and collection days except cynomolgus macaques on day 1. This saliva collection device allows quick and reliable sample collection for the determination of salivary cortisol levels. In addition, the results might provide a useful tool for evaluating hypothalamic-pituitary-adrenal axis activity or the physiologic stress reaction in NHP as well as a biomarker of psychologic stress states in a variety of situations. PMID:28315649

Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

Laffins, Michael M; Mellal, Nacera; Almlie, Cynthia L; Regalia, Douglas E

2017-01-01

Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations. Infrared measurements were taken 5 cm from the chest and inguinal areas. We evaluated 10 (9 functional devices) sedated cynomolgus macaques (5 male, 5 female) implanted with telemetry units in a muscular pouch between the internal and external abdominal oblique muscles. We determined that the mean body temperature acquired by using telemetry did not differ from either the mean of inguinal and chest infrared measurements but did differ from the mean of temperature obtained rectally. In addition, the mean rectal temperature differed from the mean of the inguinal reading but not the mean of the chest temperature. The results confirm our hypothesis that the infrared thermometer can be used to replace standard rectal thermometry. PMID:28905720

Osseointegration of dental implants in Macaca fascicularis

NASA Astrophysics Data System (ADS)

Dewi, R. S.; Odang, R. W.; Odelia, L.

2017-08-01

Osseointegration is an important factor in determining the success of a dental implant. It can be assessed from the osseointegration that occurs between the implant and the bone. The implant stability is determined by the osseous support at the implant-bone interface, which is commonly evaluated by histomorphometric analysis. This study aimed to evaluate whether the osseointegration level measured by a Low Resonance Frequency Analyzer (LRFA) gave results as good as those obtained by histomorphometric examination. Six male Macaca fascicularis were used in this study. In each animal, two types of loading were performed: immediate and delayed loading. Clinical examination and LRFA measurement were performed to determine osseointegration at the first and second weeks and at the first, second, third, and fourth months. After four months, histomorphometric examination was performed. The relationship between the histomorphometric examination and LRFA measurement was compared using the Pearson correlation coefficient. There was no significant difference in the osseointegration between immediate loading and delayed loading (p > 0.05) The bone-implant contact percentage in the first group did not differ significantly from that in the second group. Statistical analysis showed that there was a strong correlation between LRFA measurement and histomorphometric examination. Osseointegration could be evaluated through LRFA measurement as well as through histomorphometric examination.

Finding the Factors of Reduced Genetic Diversity on X Chromosomes of Macaca fascicularis: Male-Driven Evolution, Demography, and Natural Selection

PubMed Central

Osada, Naoki; Nakagome, Shigeki; Mano, Shuhei; Kameoka, Yosuke; Takahashi, Ichiro; Terao, Keiji

2013-01-01

The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.34 and 0.20 in the Indonesian–Malaysian and Philippine populations, respectively, considerably lower than the null expectation of 0.75. A Philippine population supposed to derive from an ancestral population by founding events showed a significantly lower ratio than the parental population, suggesting a demographic effect for the reduction. Taking sex-specific mutation rate bias and demographic effect into account, expected X/A diversity ratios generated by computer simulations roughly agreed with the observed data in the intergenic regions. In contrast, silent sites in genic regions on X chromosomes showed strong reduction in genetic diversity and the observed X/A diversity ratio in the genic regions cannot be explained by mutation rate bias and demography, indicating that natural selection also reduces the level of polymorphism near genes. Whole-genome analysis of a female cynomolgus monkey also supported the notion of stronger reduction of genetic diversity near genes on the X chromosome. PMID:24026095

Testicular Fibrous Hypoplasia in Cynomolgus Monkeys ( Macaca fascicularis): An Incidental, Congenital Lesion.

PubMed

Pereira Bacares, Marcia E; Vemireddi, Vimala; Creasy, Dianne

2017-06-01

Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.

Limited Susceptibility of Cynomolgus Monkeys (Macaca fascicularis) to Leprosy after Experimental Administration of Mycobacterium leprae

PubMed Central

Walsh, Gerald P.; Dela Cruz, Eduardo C.; Abalos, Rodolfo M.; Tan, Esterlina V.; Fajardo, Tranquilino T.; Villahermosa, Laarni G.; Cellona, Roland V.; Balagon, Maria V.; White, Valerie A.; Saunderson, Paul R.; Walsh, Douglas S.

2012-01-01

Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis—importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1–19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration. PMID:22855766

Antibody Responses in the Nonhuman Primate, Macaca Fascicularis, to Protein Toxins

DTIC Science & Technology

1990-05-01

generation of tetanus-specific antibody, producing B cells after in vivo immunization of Crohn’s dis- ease and ulcerative colitis patients ...lty Codes APPROVED: Noat eoa Sanford Millef, Ph.D. Dean CON;’ DEDICATION 1 his thesis is dedicated to the ones who so patiently tucked away their...were expermentally infected with Brugia milayi, a human filarial parasite , and antibody levels followed by enzyme linked immunosorbant assay (ELISA

Establishment and characterization of Macaca fascicularis lymphoblastoid cell lines.

PubMed

Manning, C H; Heise, E R

1992-01-01

A panel of cynomolgus macaque lymphoblastoid cell lines (LCL) was established by transforming peripheral blood mononuclear cells (PBMC) with Herpesvirus papio (HVP), and selected lines were examined by flow cytometry. Results indicate that HVP-transformed macaque LCL are phenotypically heterogeneous and resemble human Epstein-Barr virus (EBV)-transformed LCL in the abundant expression of major histocompatibility complex (MHC) class I and class II molecules. At least some lines are of B cell origin.

Absorbed radiation dosimetry of the D3-specific PET radioligand [18F]FluorTriopride estimated using rodent and nonhuman primate

PubMed Central

Laforest, Richard; Karimi, Morvarid; Moerlein, Stephen M; Xu, Jinbin; Flores, Hubert P; Bognar, Christopher; Li, Aixiao; Mach, Robert H; Perlmutter, Joel S; Tu, Zhude

2016-01-01

[18F]FluorTriopride ([18F]FTP) is a dopamine D3-receptor preferring radioligand with potential for investigation of neuropsychiatric disorders including Parkinson disease, dystonia and schizophrenia. Here we estimate human radiation dosimetry for [18F]FTP based on the ex-vivo biodistribution in rodents and in vivo distribution in nonhuman primates. Biodistribution data were generated using male and female Sprague-Dawley rats injected with ~370 KBq of [18F]FTP and euthanized at 5, 30, 60, 120, and 240 min. Organs of interest were dissected, weighed and assayed for radioactivity content. PET imaging studies were performed in two male and one female macaque fascicularis administered 143-190 MBq of [18F]FTP and scanned whole-body in sequential sections. Organ residence times were calculated based on organ time activity curves (TAC) created from regions of Interest. OLINDA/EXM 1.1 was used to estimate human radiation dosimetry based on scaled organ residence times. In the rodent, the highest absorbed radiation dose was the upper large intestines (0.32-0.49 mGy/MBq), with an effective dose of 0.07 mSv/MBq in males and 0.1 mSv/MBq in females. For the nonhuman primate, however, the gallbladder wall was the critical organ (1.81 mGy/MBq), and the effective dose was 0.02 mSv/MBq. The species discrepancy in dosimetry estimates for [18F]FTP based on rat and primate data can be attributed to the slower transit of tracer through the hepatobiliary track of the primate compared to the rat, which lacks a gallbladder. Out findings demonstrate that the nonhuman primate model is more appropriate model for estimating human absorbed radiation dosimetry when hepatobiliary excretion plays a major role in radiotracer elimination. PMID:28078183

Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration.

PubMed

Grant, Kathleen A; Leng, Xiaoyan; Green, Heather L; Szeliga, Kendall T; Rogers, Laura S M; Gonzales, Steven W

2008-10-01

We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent "spree" drinking (intakes >4.0 g/kg/d). This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into chronic heavy alcohol consumption in primates (drinking the equivalent of 16 to 20 drinks per day). The model may aid in identifying biological risks for establishing harmful alcohol drinking.

Drinking Typography Established by Scheduled Induction Predicts Chronic Heavy Drinking in a Monkey Model of Ethanol Self-Administration

PubMed Central

Grant, Kathleen A.; Leng, Xiaoyan; Green, Heather L.; Szeliga, Kendall T.; Rogers, Laura S. M.; Gonzales, Steven W.

2010-01-01

Background We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Methods Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Results Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent “spree” drinking (intakes >4.0 g/kg/d). Conclusion This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into chronic heavy alcohol consumption in primates (drinking the equivalent of 16 to 20 drinks per day). The model may aid in identifying biological risks for establishing harmful alcohol drinking. PMID:18702645

Stimulus-Food Pairings Produce Stimulus-Directed Touch-Screen Responding in Cynomolgus Monkeys (MACACA Fascicularis) With or Without a Positive Response Contingency

DTIC Science & Technology

2009-07-01

REPORT NUMBER US Army Medical Research Institute of Chemical Defense ATTN: MCMR-CDT-N 3100 Ricketts Point Road Aberdeen Proving Ground, MD...Medical Research Institute of Chemical Defense Aberdeen Proving Ground, MD 21010-5400 ATTN: MCMR-CDZ-I 11. SPONSOR/MONITOR’S REPORT 3100 Ricketts...CONTINGENCY CHRISTOPHER E. BULLOCK AND TODD M. MYERS UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE Acquisition and maintenance of

Microspectrophotometric demonstration of four classes of photoreceptor in an old world primate, Macaca fascicularis.

PubMed Central

Bowmaker, J K; Dartnall, H J; Mollon, J D

1980-01-01

1. Microspectrophotometric measurements reveal four classes of photoreceptor in the retina of the cynomolgus monkey, Macaca fascicularis, which is known to possess colour vision similar to that of a normal human trichromat. 2. Although the eyes were removed in bright illumination, the densities of pigment were comparable to those we have measured in dark-adapted rhesus retinae. 3. The mean wave-lengths of peak sensitivity (lambda max) for the four classes of photoreceptor were 415, 500, 535 and 567 nm. 4. The band widths of the absorbance spectra decreased linearly as the wave-number of peak sensitivity decreased. 5. If, by assuming a reasonable value for the axial density of the rod outer segment and correcting for lens absorption, a spectral sensitivity for human vision is reconstructed from the P500 pigment, it is found to be systematically broader than the CIE scotopic sensitivity function. 6. Given explicit assumptions, it is possible from the P535 and P567 pigments to reconstruct human psychophysical sensitivities that resemble the pi 4 and pi 5 mechanisms of W. S. Stiles. 7. Although the P415 pigment has a lambda max much shorter than that of the psychophysically measured blue mechanisms, the two spectral-sensitivity functions are brought into proximity when the microspectrophotometric data are corrected for absorption by the optic media. Images Fig. 1 PMID:6767023

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.

PubMed

Kimani, S; Moterroso, V; Morales, P; Wagner, J; Kipruto, S; Bukachi, F; Maitai, C; Tshala-Katumbay, D

2014-04-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~2× relative to that of rodents. The nervous system susceptibility to cyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet

PubMed Central

Kimani, S.; Moterroso, V.; Morales, P.; Wagner, J.; Kipruto, S.; Bukachi, F.; Maitai, C.; Tshala-Katumbay, D.

2014-01-01

We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5 mg/kg bw) or NaOCN (50 mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~ 80X faster in the nervous system (14 milliseconds to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In macaca fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; p<0.001). The plasma CDC was ~ 2X relative to that of rodents. The nervous system susceptibility to cyanide may result from a “multiple hit” by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. PMID:24500607

Chitinase mRNA Levels Determined by QPCR in Crab-Eating Monkey (Macaca fascicularis) Tissues: Species-Specific Expression of Acidic Mammalian Chitinase and Chitotriosidase.

PubMed

Uehara, Maiko; Tabata, Eri; Ishii, Kazuhiro; Sawa, Akira; Ohno, Misa; Sakaguchi, Masayoshi; Matoska, Vaclav; Bauer, Peter O; Oyama, Fumitaka

2018-05-09

Mice and humans express two active chitinases: acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Both chitinases are thought to play important roles in specific pathophysiological conditions. The crab-eating monkey ( Macaca fascicularis ) is one of the most frequently used nonhuman primate models in basic and applied biomedical research. Here, we performed gene expression analysis of two chitinases in normal crab-eating monkey tissues by way of quantitative real-time polymerase chain reaction (qPCR) using a single standard DNA molecule. Levels of AMCase and CHIT1 messenger RNAs (mRNAs) were highest in the stomach and the lung, respectively, when compared to other tissues. Comparative gene expression analysis of mouse, monkey, and human using monkey⁻mouse⁻human hybrid standard DNA showed that the AMCase mRNA levels were exceptionally high in mouse and monkey stomachs while very low in the human stomach. As for the CHIT1 mRNA, we detected higher levels in the monkey lung when compared with those of mouse and human. The differences of mRNA expression between the species in the stomach tissues were basically reflecting the levels of the chitinolytic activities. These results indicate that gene expression of AMCase and CHIT1 differs between mammalian species and requiring special attention in handling data in chitinase-related studies in particular organisms.

Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis).

PubMed

Ballesta, Sébastien; Reymond, Gilles; Pozzobon, Matthieu; Duhamel, Jean-René

2016-01-01

3,4-methylenedioxy-N-methyl amphetamine (MDMA) is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg) to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). In addition, received and given social grooming was manually scored. Results show several significant dose-dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates' social behaviors.

A preliminary study on activity budget, daily travel distance and feeding behaviour of long-tailed macaques and spectacled dusky leaf monkey in Bangi campus of Universiti Kebangsaan Malaysia, Selangor

NASA Astrophysics Data System (ADS)

Ruslin, Farhani; Yaakop, Salmah; Zain, Badrul Munir Md.

2014-09-01

The activity budget, ranging behaviour and feeding behaviour of a multimale-multifemale group of long-tailed macaques (Macaca fascicularis) and a multimale-multifemale group of spectacled dusky leaf monkey (Trachypithecus obscurus) were studied. A total of 145 hours and 143 hours have been spent to observe the group of long-tailed macaque and spectacled dusky leaf monkey that ranged the same habitat adjacent to the campus areas. The researchers examined the activity budgets, daily travel length and feeding activity of both species and distinguished how the sympatric species used the same forested habitat. Preliminary study found that the long-tailed macaques spent longer time feeding, moving than resting and other activities. On the other hand, the dusky leaf monkey spent much time in feeding and resting than moving. The differences of daily pattern between these two groups are significant. Macaques have higher daily mean of path length compared to the dusky leaf monkey and spent much time moving compare to the leaf monkey group. The spectacled dusky leaf monkey group also has fully utilized the forested areas where else the long-tailed macaques adopted foraging to the adjacent residential colleges.

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

DTIC Science & Technology

2010-09-01

and interstitial fibrosis, and fibrous pleural adhesions. Other lesions included lymphoid hyperplasia and plasmacytosis, and chronic periadnexal and...inflammation in the lung and mediastinal lymph nodes, chronic inflammation centered on bronchi and vessels, type II pneumocyte hyperplasia , pleural...2/6 33 1/6 16 1/3 33 spleen splenitis, necrotizing 1/3 33 2/6 33 4/6 66 2/3 66 lymphoid depletion 2/3 66 3/6 50 3/6 50 2/3 66 lymphoid hyperplasia * 0

Sequence of Reston Virus Isolate AZ-1435, an Ebolavirus Isolate Obtained during the 1989-1990 Reston Virus Epizootic in the United States.

PubMed

Cornish, Joseph P; Diaz, Larissa; Ricklefs, Stacy M; Kanakabandi, Kishore; Sword, Jennifer; Jahrling, Peter B; Kuhn, Jens H; Porcella, Stephen F; Johnson, Reed F

2017-01-12

Reston virus (RESTV) was discovered in 1989-1990 during three connected epizootics of highly lethal viral hemorrhagic fever among captive macaques in primate housing facilities in the United States and Philippines. Currently, only one RESTV isolate from that outbreak (named Pennsylvania) has been sequenced. Here, we report the sequence of a second isolate, Reston virus/M.fascicularis-tc/USA/1990/Philippines89-AZ1435. Copyright © 2017 Cornish et al.

Omental anatomy of non-human primates.

PubMed

Chaffanjon, Philippe C J; Kenyon, Norman M; Ricordi, Camillo; Kenyon, Norma S

2005-11-01

The anatomy and physiology of the omentum provide optimum reconstructive characteristics and the omentum may be used as a free or pedicled autograft, but also as the receptor site for engraftment of glandular islets. Our purpose was the study of the omental anatomy of non-human primate (NHP), in order to determine an experimental model for pancreatic islets transplantation. Seventeen cadavers NHP (age range 4 years to 23 years) were utilised in this anatomical study. Both cynomolgus monkeys (macaca fascicularis) and baboons (papio hamadryas) were analysed. The animals were without known medical or anatomical abnormalities. We studied the morphology of the omentum, with an emphasis on arterial vascularisation. The omental anatomy of the NHP is very similar to that of humans. The main difference lies in the shape of the lesser sac, which has a complete caudal recess. The arterial vascularisation has a double origin. Based on the anastomosis between them and on the vascular density, the NHP omentum can be divided into four vascular areas. Our results demonstrate that one or two long pedicled flaps can be constructed from the omentum.

Compete to Play: Trade-Off with Social Contact in Long-Tailed Macaques (Macaca fascicularis)

PubMed Central

Ballesta, Sébastien; Reymond, Gilles; Pozzobon, Mathieu; Duhamel, Jean-René

2014-01-01

Many animal species engage in various forms of solitary object play, but this activity seems to be of particular importance in primates. If playing objects constitute a valuable resource, and access to such objects is limited, a competitive context may arise. We inserted a unique toy within a mini-colony of long-tailed macaque (Macaca fascicularis) and compared their behaviors to sessions without playing object. An automatic color-based 3D video device was used to track the positions of each animal and the toy, and this data was categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). As expected, the delay to first access to the object reflected the hierarchy of the colony, indicating that a competition took place to own this unique resource of entertainment. In addition, we found that the amount of object play was not correlated with social or foraging behavior, suggesting independent motivational mechanisms. Conversely, object playing time was negatively correlated with idling time, thus indicating its relation to pastime activities. Interestingly, the amount of social contacts in the group was significantly reduced by the heightened competitive context, suggesting that competitors are more likely to be perceived as potential threat requiring caution, as shown in humans. Experimental manipulation of competitive contexts in primates reveals common mental processes involved in social judgment, and shows that access to valuable resources can be a sufficient cause for variations in group cohesion. PMID:25551755

Investigating biogeographic boundaries of the Sunda shelf: A phylogenetic analysis of two island populations of Macaca fascicularis.

PubMed

Klegarth, A R; Sanders, S A; Gloss, A D; Lane-deGraaf, K E; Jones-Engel, L; Fuentes, A; Hollocher, H

2017-08-01

Cyclical submergence and re-emergence of the Sunda Shelf throughout the Pleistocene served as a dynamic biogeographic landscape, across which long-tailed macaques (Macaca fascicularis) have migrated and evolved. Here, we tested the integrity of the previously reported continental-insular haplotype divide reported among Y and mitochondrial DNA lineages across multiple studies. The continental-insular haplotype divide was tested by heavily sampling wild macaques from two important biogeographic regions within Sundaland: (1) Singapore, the southernmost tip of continental Asia and (2) Bali, Indonesia, the southeastern edge of the Indonesian archipelago, immediately west of Wallace's line. Y DNA was haplotyped for samples from Bali, deep within the Indonesian archipelago. Mitochondrial D-loop from both islands was analyzed against existing data using Maximum Likelihood and Bayesian approaches. We uncovered both "continental" and "insular" Y DNA haplotypes in Bali. Between Singapore and Bali we found 52 unique mitochondrial haplotypes, none of which had been previously described. Phylogenetic analyses confirmed a major haplogroup division within Singapore and identified five new Singapore subclades and two primary subclades in Bali. While we confirmed the continental-insular divide among mtDNA haplotypes, maintenance of both Y DNA haplotypes on Bali, deep within the Indonesian archipelago calls into question the mechanism by which Y DNA diversity has been maintained. It also suggests the continental-insular designation is less appropriate for Y DNA, leading us to propose geographically neutral Y haplotype designations. © 2017 Wiley Periodicals, Inc.

Colour cues for leaf food selection by long-tailed macaques (Macaca fascicularis) with a new suggestion for the evolution of trichromatic colour vision.

PubMed

Lucas, P W; Darvell, B W; Lee, P K; Yuen, T D; Choong, M F

1998-01-01

Leaf colour, size and toughness were investigated in five plant species important in the diet of Macaca fascicularis in Singapore. Leaf colour and size were examined as potential visual cues for food selection, whereas toughness mirrored fibre content, the inverse of food quality. As leaves matured, they changed colour and toughened. Leaf lightness and yellowness were strongly negatively correlated with toughness, but variation in both the red-green axis of the CIE Lab colour space and leaf size were not. Leaves selected as food by the macaques were distinguished by being very light, yellow to slightly green. Some leaves were dappled with red. The literature suggests that these leaves are relatively rich in protein without being tough and therefore would be sought after by primates. We argue that leaf colour is an important indicator of the nutritive value of leaves. Trichromatic vision is an important advantage in finding those palatable leaves that are dappled red. These would appear dark to dichromatic primates and be deceptive by making leaves look older (lower in quality) than they actually are. This would decrease the perceived window of feeding opportunity for such primates who would be at a disadvantage in trying to find these leaves. It is possible that trichromatic vision in catarrhine primates may have originally evolved for the detection of red coloration in the leaves of shade-tolerant tropical plants, enabling the better exploitation of a food resource.

Highly heterogeneous bacterial communities associated with the South China Sea reef corals Porites lutea, Galaxea fascicularis and Acropora millepora.

PubMed

Li, Jie; Chen, Qi; Zhang, Si; Huang, Hui; Yang, Jian; Tian, Xin-Peng; Long, Li-Juan

2013-01-01

Coral harbor diverse and specific bacteria play significant roles in coral holobiont function. Bacteria associated with three of the common and phylogenetically divergent reef-building corals in the South China Sea, Porites lutea, Galaxea fascicularis and Acropora millepora, were investigated using 454 barcoded-pyrosequencing. Three colonies of each species were sampled, and 16S rRNA gene libraries were constructed individually. Analysis of pyrosequencing libraries showed that bacterial communities associated with the three coral species were more diverse than previous estimates based on corals from the Caribbean Sea, Indo-Pacific reefs and the Red Sea. Three candidate phyla, including BRC1, OD1 and SR1, were found for the first time in corals. Bacterial communities were separated into three groups: P. lutea and G. fascicular, A. millepora and seawater. P. lutea and G. fascicular displayed more similar bacterial communities, and bacterial communities associated with A. millepora differed from the other two coral species. The three coral species shared only 22 OTUs, which were distributed in Alphaproteobacteria, Deltaproteobacteria, Gammaproteobacteria, Chloroflexi, Actinobacteria, Acidobacteria and an unclassified bacterial group. The composition of bacterial communities within each colony of each coral species also showed variation. The relatively small common and large specific bacterial communities in these corals implies that bacterial associations may be structured by multiple factors at different scales and that corals may associate with microbes in terms of similar function, rather than identical species.

D-phenylalanine: a putative enkephalinase inhibitor studied in a primate acute pain model.

PubMed

Halpern, L M; Dong, W K

1986-02-01

D-Phenylalanine, along with morphine, acetylsalicylic acid and zomepirac sodium were evaluated for their antinociceptive actions in monkeys (M. fascicularis) trained to autoregulate nociceptive stimulation using a discrete-trials, aversive-threshold paradigm. Morphine sulfate produced dose-related increases in aversive threshold which were reversible after administration of naloxone (12.5 or 25 micrograms/kg i.m.). D-Phenylalanine (500 mg/kg p.o.) produced a small increase in aversive threshold which was not statistically significant and not naloxone reversible. Acetylsalicylic acid (200 mg/kg p.o.) but not zomepirac sodium (200 mg/kg p.o.) in combination with D-phenylalanine (500 mg/kg) produced a small statistically significant increase in aversive threshold. Our results argue against the hypothesis that D-phenylalanine is responsible for increasing aversive thresholds via opiate receptor mechanisms involving increased activity of enkephalins at synaptic loci. Previous studies by others in rats and mice showed that D-phenylalanine and acetylsalicylic acid produced increases in nociceptive thresholds which were naloxone reversible. Our failure to find opiate receptor mediated analgesia in a primate model with demonstrated opiate receptor selectivity and sensitivity is discussed in terms of previous basic and clinical research indicating an analgesic role for D-phenylalanine. Possible species difference in drug action is discussed in terms of inhibition by D-phenylalanine of carboxy-peptidase-like enkephalin processing enzymes as well as inhibition of carboxypeptidase-like enkephalin degrading enzymes.

Stress in cynomolgus monkeys (Macaca fascicularis) subjected to long-distance transport and simulated transport housing conditions.

PubMed

Fernström, A L; Sutian, W; Royo, F; Westlund, K; Nilsson, T; Carlsson, H-E; Paramastri, Y; Pamungkas, J; Sajuthi, D; Schapiro, S J; Hau, J

2008-11-01

The stress associated with transportation of non-human primates used in scientific research is an important but almost unexplored part of laboratory animal husbandry. The procedures and routines concerning transport are not only important for the animals' physical health but also for their mental health as well. The transport stress in cynomolgus monkeys (Macaca fascicularis) was studied in two experiments. In Experiment 1, 25 adult female cynomolgus monkeys were divided into five groups of five animals each that received different diets during the transport phase of the experiment. All animals were transported in conventional single animal transport cages with no visual or tactile contact with conspecifics. The animals were transported by lorry for 24 h at ambient temperatures ranging between 20 degrees C and 35 degrees C. Urine produced before, during and after transport was collected and analysed for cortisol by enzyme-linked immunosorbent assay (ELISA). All monkeys exhibited a significant increase in cortisol excretion per time unit during the transport and on the first day following transport.Although anecdotal reports concerning diet during transport, including the provision of fruits and/or a tranquiliser, was thought likely to influence stress responses, these were not corrobated by the present study. In Experiment 2, behavioural data were collected from 18 cynomolgus macaques before and after transfer from group cages to either single or pair housing, and also before and after a simulated transport, in which the animals were housed in transport cages. The single housed monkeys were confined to single transport cages and the pair housed monkeys were kept in their pairs in double size cages. Both pair housed and singly housed monkeys showed clear behavioural signs of stress soon after their transfer out of their group cages.However, stress-associated behaviours were more prevalent in singly housed animals than in pair housed animals, and these behaviours persisted for a longer time after the simulated transport housing event than in the pair housed monkeys. Our data confirm that the transport of cynomolgus monkeys is stressful and suggest that it would be beneficial for the cynomolgus monkeys to be housed and transported in compatible pairs from the time they leave their group cages at the source country breeding facility until they arrive at their final laboratory destination in the country of use.

[Ultrastructural observation on nymphal Armillifer sp. by scanning electron microscopy and phylogenetic analysis based on 18S rRNA].

PubMed

Li, Jian; Shi, Yun-Liang; Shi, Wei; Fang, Fang; Zhou, Qing-An; Li, Wen-Wen; He, Guo-Sheng; Huang, Wei-Yi

2012-04-30

To observe the ultrastructure of nymphal Armillifer sp. isolated from Macaca fascicularis by using scanning electron microscope (SEM), and analyze the phylogenetic relationships based on 18S rRNA gene sequences. The parasite samples stored in 70% alcohol were fixed by glutaraldehyde and osmium peroxide. Ultrastructural characters of those samples were observed under SEM. Amplification and sequencing of the 18S rRNA gene were performed following the extraction of total genome DNA. Sequence analysis was performed based on multiple alignment using ClustalX1.83, while phylogenetic analysis was made by Neighbor-Joining method using MEGA4.0. The nymphs were in cylindrical shape, the body slightly claviform tapering to posterior end. Abdominal annuli were gradually widened from anterior to posterior parts, the 12th-13th abdominal annuli of which were similar in width. The annuli ranged closer in the front half body, whereas in the latter part there were certain gaps between them. The circular-shaped mouth located in the middle of head ventrally. Folds were seen in inner margin of the mouth with a pair of curved hooks on both sides above it which practically disposed in a straight line. Two pairs of large sensory papillae were observed symmetrically over the last thoracic annulus of cephalothoraxs lying below the outer hook, and the first abdominal annulus was near the median ventral line. The number of abdominal annuli was 29, not including 2 incomplete terminal annuli. Rounded sensory papillae were fully distributed on the body surface, except the dorsal side of head and the ventral part of the terminal annulus. Agglomerate-like anus opening was observed at the end of ventral abdominal annuli and distinctly sub-terminal. These morphological features demonstrated that the nymphs were highly similar with that of Armillifer moniliformis Diesing, 1835. A fragment of 18SrRNA gene (1 836 bp) sequences was obtained by PCR combined with sequencing, and was registered to the GeneBank database with an accession number HM048870. The phylogenetic tree indicated that A. moniliformis, A.agkistrodon and A.armillatus were at the same clade with a bootstrap value at 95%, and A. moniliformis and A. agkistrodon were solo at a clade with a bootstrap value of 75%. The nymphs isolated from Macaca fascicularis are identified as A. moniliformis temporarily.

Antagonism of the Ethanol-Like Discriminative Stimulus Effects of Ethanol, Pentobarbital, and Midazolam in Cynomolgus Monkeys Reveals Involvement of Specific GABAA Receptor SubtypesS⃞

PubMed Central

Rogers, Laura S. M.; Grant, Kathleen A.

2009-01-01

The γ-aminobutyric acid (GABA)A receptors mediating the discriminative stimulus effects of ethanol were studied by comparing the potency of ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)benzodiazepine-3-carboxylate (Ro15-4513) and ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)-benzodiazepine-3-carboxylate (flumazenil, Ro15-1788) to antagonize ethanol, pentobarbital (PB), and midazolam substitution for ethanol. Ro15-4513 has high affinity for receptors containing α4/6 and α5 subunits and lower affinity for α1, α2, and α3 subunits. Flumazenil is nonselective for GABAA receptors containing α1, α2, α3, and α5 subunits and has low affinity for α4/6-containing receptors. Male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) were trained to discriminate ethanol (1.0 or 2.0 g/kg i.g., 30-min pretreatment) from water. Ethanol, PB, and midazolam dose-dependently substituted for ethanol (80% ethanol-appropriate responding). Ro15-4513 (0.003–0.56 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in a vast majority of monkeys tested (15/15, 16/17, and 11/12, respectively). In contrast, flumazenil (0.30–10.0 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in 9 of 16, 12 of 16, and 7 of 9 monkeys tested, respectively. In the monkeys showing antagonism with both Ro15-4513 and flumazenil, ethanol and PB substitution were antagonized more potently by Ro15-4513 than by flumazenil, whereas midazolam substitution was antagonized with similar potency. There were no sex or training dose differences, with the exception that flumazenil failed to antagonize ethanol substitution in males trained to discriminate 2.0 g/kg ethanol. GABAA receptors with high affinity for Ro15-4513 (i.e., containing α4/6 and α5 subunits) may be particularly important mediators of the multiple discriminative stimulus effects of ethanol through GABAA receptor systems. PMID:19641166

Sex differences in the stone tool-use behavior of a wild population of burmese long-tailed macaques (Macaca fascicularis aurea).

PubMed

Gumert, Michael D; Hoong, Low Kuan; Malaivijitnond, Suchinda

2011-12-01

We investigated sex differences in how Burmese long-tailed macaques (Macaca fascicularis aurea) used stone tools to open shelled food items along the shores of two islands in Laemson National Park, Thailand. Over a 2-week period in December 2009, we collected scan and focal samples on macaques when they were visible along the shores and mangroves. We found females used stones more often while feeding and used smaller tools than males. Females also processed sessile oysters more than males, whereas males processed unattached foods more than females. It was unclear which sex was overall more proficient at stone tool use, but males did perform significantly better at opening unattached food items with large pounding stones. Females also struck food items more times during tool-use bouts and at a faster rate, but no significant difference was found in average tool-use bout duration. Males processed foods slightly faster within a tool-use bout, but we were unable to detect a significant difference in the rate of food processing while foraging with tools. In summary females chipped open sessile oysters with an axing technique more than males, while males used larger stones to pound open unattached shelled food more often than females. Despite using pounding more than females, males also regularly utilized the axing technique on sessile oysters. Our results are the first assessment of sex differences in macaque stone tool use, providing a basis for comparison with tool use in other primates, and to nonfunctional forms of stone use in other macaques. © 2011 Wiley Periodicals, Inc.

Ultrastructural study of the primary olfactory pathway in Macaca fascicularis.

PubMed

Herrera, Loren P; Casas, Carlos E; Bates, Margaret L; Guest, James D

2005-08-08

Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within the olfactory pathway. OEGs are thought to exclude OAs from contact with all other cells between the olfactory epithelium and the glomerulus of the olfactory bulb. These properties have lead to testing to determine whether OEGs support axonal growth following transplantation. The cellular interactions of transplanted OEGs will probably resemble those that occur within the normal pathway where interactions between OEGs and fibroblasts are prominent. No previous primate studies have focused on these interactions, knowledge of which is important if clinical application is envisioned. We describe the detailed intercellular interactions of OAs with supporting cells throughout the olfactory epithelium, the lamina propria, the fila olfactoria, and the olfactory nerve layer by using transmission electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment and variations of the endo- and perineurium formed by olfactory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. Perineurial cells contained intermediate filaments and were distinct from other fibroblasts and meningeal cells. OAs had direct contacts with astrocytes near the glia limitans. The properties of OEGs differed depending on whether astrocytic or fibroblastic processes were present. This indicates the importance of the cellular milieu in the structure and function of OEGs in primates.

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

PubMed

Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

2015-10-01

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

A simple orchidometric method for the preliminary assessment of maturity status in male cynomolgus monkeys (Macaca fascicularis) used for nonclinical safety studies.

PubMed

Ku, Warren W; Pagliusi, Frank; Foley, George; Roesler, Alfred; Zimmerman, Thomas

2010-01-01

The identification and use of mature male non-human primates in nonclinical toxicology studies could be important for evaluating candidate drugs for which the profile of toxicity may differ depending on sexual maturity. This investigation sought to establish operational criteria to complement the current standard of histological evaluation for defining sexual maturity in male cynomolgus monkeys (Macaca fascicularis) used for toxicology studies, and to identify a practical non-invasive measure to select mature males for study. Retrospectively, the relationships between body weight, testicular weight and testis histology were established in control males (n=126) used in previous toxicology studies. Prospectively, testicular volumes were measured in-life by orchidometry using comparative scrotal palpation (n=23 males used for study), then compared to testicular weights measured at necropsy. Consistent with previous literature, a weak relationship was observed between body weight and testicular weight. There was, however, a very good relationship between testicular weight and histological maturation level, which was based upon microscopic examination of testes, epididymides and prostates. Orchidometric measurement of testicular volume was found to be a reasonable predictor of testicular weight and served to rapidly select sexually mature males for study, and a total testicular volume (left and right combined) of >20 ml correlated with the histological appearance of maturity. Based upon this preliminary exploratory study, the initial simple measurement of testicular volume by orchidometry may provide a non-invasive alternative approach for assessing the sexual maturity of male cynomolgus monkeys in research colonies or during toxicology studies that will require more thorough validation. Copyright 2009 Elsevier Inc. All rights reserved.

Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication

PubMed Central

Amado, Luciane A; Marchevsky, Renato S; de Paula, Vanessa S; Hooper, Cleber; Freire, Marcos da S; Gaspar, Ana Maria C; Pinto, Marcelo A

2010-01-01

This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi). Liver samples, submandibular salivary gland, mesenteric lymph node and tonsils were removed for virological and pathological evaluation. Immunofluorescence analyses on liver and salivary gland sections using confocal laser scanning microscopy revealed the presence of HAV antigen (HAV Ag). The presence of HAV genome was monitored by real-time PCR. The HAV RNA was detected at 7 days postinoculation (dpi), concomitantly in serum, saliva and faeces. The highest HAV viral load was observed in faeces at 15 dpi (105 copies/ml), followed by serum viral load of 104 copies/ml at 20 dpi and saliva viral load of 103copies/ml at 7 dpi. The animals showed first histological and biochemical signs of hepatitis at 15 dpi. The HAV antigen (Ag) was present from day 7 until day 60 pi in the liver and salivary glands. The HAV replicative intermediate was also detected in the liver (4.5 × 104 copies/mg), salivary glands (1.9 × 103 copies/mg), tonsils (4.2 × 101 copies/mg) and lymph nodes (3.4 × 101 copies/mg). Our data demonstrated that the salivary gland as an extrahepatic site of early HAV replication could create a potential risk of saliva transmitted infection. In addition, the cynomolgus monkey was confirmed as a suitable model to study the pathogenesis of HAV human infection. PMID:20096073

Impacts of Sediments on Coral Energetics: Partitioning the Effects of Turbidity and Settling Particles

PubMed Central

Junjie, Reef K.; Browne, Nicola K.; Erftemeijer, Paul L. A.; Todd, Peter A.

2014-01-01

Sediment loads have long been known to be deleterious to corals, but the effects of turbidity and settling particles have not previously been partitioned. This study provides a novel approach using inert silicon carbide powder to partition and quantify the mechanical effects of sediment settling versus reduced light under a chronically high sedimentary regime on two turbid water corals commonly found in Singapore (Galaxea fascicularis and Goniopora somaliensis). Coral fragments were evenly distributed among three treatments: an open control (30% ambient PAR), a shaded control (15% ambient PAR) and sediment treatment (15% ambient PAR; 26.4 mg cm−2 day−1). The rate of photosynthesis and respiration, and the dark-adapted quantum yield were measured once a week for four weeks. By week four, the photosynthesis to respiration ratio (P/R ratio) and the photosynthetic yield (Fv/Fm) had fallen by 14% and 3–17% respectively in the shaded control, contrasting with corals exposed to sediments whose P/R ratio and yield had declined by 21% and 18–34% respectively. The differences in rates between the shaded control and the sediment treatment were attributed to the mechanical effects of sediment deposition. The physiological response to sediment stress differed between species with G. fascicularis experiencing a greater decline in the net photosynthetic yield (13%) than G. somaliensis (9.5%), but a smaller increase in the respiration rates (G. fascicularis = 9.9%, G. somaliensis = 14.2%). These different physiological responses were attributed, in part, to coral morphology and highlighted key physiological processes that drive species distribution along high to low turbidity and depositional gradients. PMID:25197883

Standardization of magnetocardiography in nonhuman primates

NASA Astrophysics Data System (ADS)

Seki, Yusuke; Muneyuki, Kenta; Kandori, Akihiko; Tsukada, Keiji; Terao, Keiji; Ageyama, Naohide

2008-03-01

To establish the electrophysiological mappings of nonhuman primates by using magnetocardiogram (MCG) data and obtain the normal values of MCG parameters, we used 64-channel superconducting quantum interference devices to measure 8 × 8 MCG data for 95 cynomolgus monkeys (Macaca fascicularis, 51 female and 44 male). The PQ interval, QRS duration, QT interval and QTc were respectively 79 ± 14 ms, 42 ± 7 ms, 222 ± 23 ms and 363 ± 25 (mean ± SD), and these parameters did not differ significantly between female and male monkeys. These results indicate the normal values of the MCG parameters of the cynomolgus monkey and should facilitate animal experiments in magnetocardiography.

Particle-to-PFU ratio of Ebola virus influences disease course and survival in cynomolgus macaques.

PubMed

Alfson, Kendra J; Avena, Laura E; Beadles, Michael W; Staples, Hilary; Nunneley, Jerritt W; Ticer, Anysha; Dick, Edward J; Owston, Michael A; Reed, Christopher; Patterson, Jean L; Carrion, Ricardo; Griffiths, Anthony

2015-07-01

This study addresses the role of Ebola virus (EBOV) specific infectivity in virulence. Filoviruses are highly lethal, enveloped, single-stranded negative-sense RNA viruses that can cause hemorrhagic fever. No approved vaccines or therapies exist for filovirus infections, and infectious virus must be handled in maximum containment. Efficacy testing of countermeasures, in addition to investigations of pathogenicity and immune response, often requires a well-characterized animal model. For EBOV, an obstacle in performing accurate disease modeling is a poor understanding of what constitutes an infectious dose in animal models. One well-recognized consequence of viral passage in cell culture is a change in specific infectivity, often measured as a particle-to-PFU ratio. Here, we report that serial passages of EBOV in cell culture resulted in a decrease in particle-to-PFU ratio. Notably, this correlated with decreased potency in a lethal cynomolgus macaque (Macaca fascicularis) model of infection; animals were infected with the same viral dose as determined by plaque assay, but animals that received more virus particles exhibited increased disease. This suggests that some particles are unable to form a plaque in a cell culture assay but are able to result in lethal disease in vivo. These results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures. Ebola virus (EBOV) can cause severe hemorrhagic disease with a high case-fatality rate, and there are no approved vaccines or therapies. Specific infectivity can be considered the total number of viral particles per PFU, and its impact on disease is poorly understood. In stocks of most mammalian viruses, there are particles that are unable to complete an infectious cycle or unable to cause cell pathology in cultured cells. We asked if these particles cause disease in nonhuman primates by infecting monkeys with equal infectious doses of genetically identical stocks possessing either high or low specific infectivities. Interestingly, some particles that did not yield plaques in cell culture assays were able to result in lethal disease in vivo. Furthermore, the number of PFU needed to induce lethal disease in animals was very low. Our results have a significant impact on how future studies are designed to model EBOV disease and test countermeasures.

Zolpidem generalization and antagonism in male and female cynomolgus monkeys trained to discriminate 1.0 or 2.0 g/kg ethanol.

PubMed

Helms, Christa M; Rogers, Laura S M; Waters, Courtney A; Grant, Kathleen A

2008-07-01

The subtypes of gamma-aminobutyric acid (GABA)(A) receptors mediating the discriminative stimulus effects of ethanol in nonhuman primates are not completely identified. The GABA(A) receptor positive modulator zolpidem has high, intermediate, and low activity at receptors containing alpha(1), alpha(2/3), and alpha(5) subunits, respectively, and partially generalizes from ethanol in several species. The partial inverse agonist Ro15-4513 has the greatest affinity for alpha(4/6)-containing receptors, higher affinity for alpha(5)- and lower, but equal, affinity for alpha(1)- and alpha(2/3)-, containing GABA(A) receptors, and antagonizes the discriminative stimulus effects of ethanol. This study assessed Ro15-4513 antagonism of the generalization of zolpidem from ethanol in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 g/kg (n = 10) or 2.0 g/kg (n = 7) ethanol (i.g.) from water with a 30-minute pretreatment interval. Zolpidem (0.017 to 5.6 mg/kg, i.m.) completely generalized from ethanol (>or=80% of total session responses on the ethanol-appropriate lever) for 6/7 monkeys trained to discriminate 2.0 g/kg and 4/10 monkeys trained to discriminate 1.0 g/kg ethanol. Zolpidem partially generalized from 1.0 or 2.0 g/kg ethanol in 6/7 remaining monkeys. Ro15-4513 (0.003 to 0.30 mg/kg, i.m., 5-minute pretreatment) shifted the zolpidem dose-response curve to the right in all monkeys showing generalization. Analysis of apparent pK(B) from antagonism tests suggested that the discriminative stimulus effects of ethanol common with zolpidem are mediated by low-affinity Ro15-4513 binding sites. Main effects of sex and training dose indicated greater potency of Ro15-4513 in males and in monkeys trained to discriminate 1.0 g/kg ethanol. Ethanol and zolpidem share similar discriminative stimulus effects most likely through GABA(A) receptors that contain alpha(1) subunits, however, antagonism by Ro15-4513 of zolpidem generalization from the lower training dose of ethanol (1.0 g/kg) may involve additional zolpidem-sensitive GABA(A) receptor subtypes (e.g., alpha(2/3) and alpha(5)).

Lens capsule structure assessed with atomic force microscopy

PubMed Central

Sueiras, Vivian M.; Moy, Vincent T.

2015-01-01

Purpose To image the ultrastructure of the anterior lens capsule at the nanoscale level using atomic force microscopy (AFM). Methods Experiments were performed on anterior lens capsules maintained in their in situ location surrounding the lens from six human cadavers (donor age range: 44–88 years), four cynomolgus monkeys (Macaca fascicularis age range: 4.83–8.92 years), and seven pigs (<6 months). Hydration of all samples was maintained using Dulbecco’s Modified Eagle Medium (DMEM). Whole lenses were removed from the eye and placed anterior side up in agarose gel before gel hardening where only the posterior half of the lens was contained within the gel. After the gel hardened, the Petri dish was filled with DMEM until the point where the intact lens was fully submerged. AFM was used to image the anterior lens surface in contact mode. An integrated analysis program was used to calculate the interfibrillar spacing, fiber diameter, and surface roughness of the samples. Results The AFM images depict a highly ordered fibrous structure at the surface of the lens capsule in all three species. The interfibrillar spacing for the porcine, cynomolgus monkey, and human lens capsules was 0.68±0.25, 1.80±0.39, and 1.08±0.25 μm, respectively. In the primate, interfibrillar spacing significantly decreased linearly as a function of age. The fiber diameters ranged from 50 to 950 nm. Comparison of the root mean square (RMS) and average deviation demonstrate that the surface of the porcine lens capsule is the smoothest, and that the human and cynomolgus monkey capsules are significantly rougher. Conclusions AFM was successful in providing high-resolution images of the nanostructure of the lens capsule samples. Species-dependent differences were observed in the overall structure and surface roughness. PMID:25814829

Network structure shapes spontaneous functional connectivity dynamics.

PubMed

Shen, Kelly; Hutchison, R Matthew; Bezgin, Gleb; Everling, Stefan; McIntosh, Anthony R

2015-04-08

The structural organization of the brain constrains the range of interactions between different regions and shapes ongoing information processing. Therefore, it is expected that large-scale dynamic functional connectivity (FC) patterns, a surrogate measure of coordination between brain regions, will be closely tied to the fiber pathways that form the underlying structural network. Here, we empirically examined the influence of network structure on FC dynamics by comparing resting-state FC (rsFC) obtained using BOLD-fMRI in macaques (Macaca fascicularis) to structural connectivity derived from macaque axonal tract tracing studies. Consistent with predictions from simulation studies, the correspondence between rsFC and structural connectivity increased as the sample duration increased. Regions with reciprocal structural connections showed the most stable rsFC across time. The data suggest that the transient nature of FC is in part dependent on direct underlying structural connections, but also that dynamic coordination can occur via polysynaptic pathways. Temporal stability was found to be dependent on structural topology, with functional connections within the rich-club core exhibiting the greatest stability over time. We discuss these findings in light of highly variable functional hubs. The results further elucidate how large-scale dynamic functional coordination exists within a fixed structural architecture. Copyright © 2015 the authors 0270-6474/15/355579-10$15.00/0.

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

PubMed

Ponce, R; Armstrong, K; Andrews, K; Hensler, J; Waggie, K; Heffernan, J; Reynolds, T; Rogge, M

2005-01-01

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

Effects of Bazedoxifene Alone and with Conjugated Equine Estrogens on Coronary and Peripheral Artery Atherosclerosis of Postmenopausal Monkeys

PubMed Central

Clarkson, Thomas B.; Ethun, Kelly F.; Chen, Haiying; Golden, Debbie; Floyd, Edison; Appt, Susan E.

2012-01-01

Objective The objective was to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atherosclerosis and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) in a monkey model. Methods Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and then randomized to receive no treatment, or women’s equivalent doses of BZA (20 mg/day), CEE (0.45 mg/day) or BZA+CEE. The experiment period was for 20 months (approximately equivalent to 5 years of patient experience) during which interim measures were made of cardiovascular risk factors. At the end of the experimental period, the extent and severity of coronary and iliac artery atherosclerosis was quantified. Results Body weight, adiposity, fasting glucose concentrations and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on coronary artery nor common iliac artery atherosclerosis extent or severity when compared to no-treatment. CEE, administered soon after inducing menopause, had a robust atheroprotective effect on both iliac and coronary artery extent and severity. The addition of BZA to the CEE treatment antagonized the atheroprotective effect of the CEE. Conclusions In this nonhuman primate trial, treatment with BZA alone, CEE alone and BZA and CEE in combination did not have significant effects on plasma lipid profiles. CEE markedly inhibited the progression and complication of both coronary and iliac artery atherosclerosis. BZA had no adverse effects on atherosclerosis but attenuated the atheroprotective effects of CEE. PMID:23435024

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.

PubMed

Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

2006-02-09

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.

Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes.

PubMed

Langley, Raymond J; Tipper, Jennifer L; Bruse, Shannon; Baron, Rebecca M; Tsalik, Ephraim L; Huntley, James; Rogers, Angela J; Jaramillo, Richard J; O'Donnell, Denise; Mega, William M; Keaton, Mignon; Kensicki, Elizabeth; Gazourian, Lee; Fredenburgh, Laura E; Massaro, Anthony F; Otero, Ronny M; Fowler, Vance G; Rivers, Emanuel P; Woods, Chris W; Kingsmore, Stephen F; Sopori, Mohan L; Perrella, Mark A; Choi, Augustine M K; Harrod, Kevin S

2014-08-15

Sepsis is a leading cause of morbidity and mortality. Currently, early diagnosis and the progression of the disease are difficult to make. The integration of metabolomic and transcriptomic data in a primate model of sepsis may provide a novel molecular signature of clinical sepsis. To develop a biomarker panel to characterize sepsis in primates and ascertain its relevance to early diagnosis and progression of human sepsis. Intravenous inoculation of Macaca fascicularis with Escherichia coli produced mild to severe sepsis, lung injury, and death. Plasma samples were obtained before and after 1, 3, and 5 days of E. coli challenge and at the time of killing. At necropsy, blood, lung, kidney, and spleen samples were collected. An integrative analysis of the metabolomic and transcriptomic datasets was performed to identify a panel of sepsis biomarkers. The extent of E. coli invasion, respiratory distress, lethargy, and mortality was dependent on the bacterial dose. Metabolomic and transcriptomic changes characterized severe infections and death, and indicated impaired mitochondrial, peroxisomal, and liver functions. Analysis of the pulmonary transcriptome and plasma metabolome suggested impaired fatty acid catabolism regulated by peroxisome-proliferator activated receptor signaling. A representative four-metabolite model effectively diagnosed sepsis in primates (area under the curve, 0.966) and in two human sepsis cohorts (area under the curve, 0.78 and 0.82). A model of sepsis based on reciprocal metabolomic and transcriptomic data was developed in primates and validated in two human patient cohorts. It is anticipated that the identified parameters will facilitate early diagnosis and management of sepsis.

SU-F-T-157: Physics Considerations Regarding Dosimetric Accuracy of Analytical Dose Calculations for Small Field Proton Therapy: A Monte Carlo Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Daartz, J

Purpose: To evaluate the accuracy of dose calculations by analytical dose calculation methods (ADC) for small field proton therapy in a gantry based passive scattering facility. Methods: 50 patients with intra-cranial disease were evaluated in the study. Treatment plans followed standard prescription and optimization procedures of proton stereotactic radiosurgery. Dose distributions calculated with the Monte Carlo (MC) toolkit TOPAS were used to represent delivered treatments. The MC dose was first adjusted using the output factor (OF) applied clinically. This factor is determined from the field size and the prescribed range. We then introduced a normalization factor to measure the differencemore » in mean dose between the delivered dose (MC dose with OF) and the dose calculated by ADC for each beam. The normalization was determined by the mean dose of the center voxels of the target area. We compared delivered dose distributions and those calculated by ADC in terms of dose volume histogram parameters and beam range distributions. Results: The mean target dose for a whole treatment is generally within 5% comparing delivered dose (MC dose with OF) and ADC dose. However, the differences can be as great as 11% for shallow and small target treated with a thick range compensator. Applying the normalization factor to the MC dose with OF can reduce the mean dose difference to less than 3%. Considering range uncertainties, the generally applied margins (3.5% of the prescribed range + 1mm) to cover uncertainties in range might not be sufficient to guarantee tumor coverage. The range difference for R90 (90% distal dose falloff) is affected by multiple factors, such as the heterogeneity index. Conclusion: This study indicates insufficient accuracy calculating proton doses using ADC. Our results suggest that uncertainties of target doses are reduced using MC techniques, improving the dosimetric accuracy for proton stereotactic radiosurgery. The work was supported by NIH/NCI under CA U19 021239. CG was partially supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087).« less

Evaluation of 16 genotype-guided Warfarin Dosing Algorithms in 310 Korean Patients Receiving Warfarin Treatment: Poor Prediction Performance in VKORC1 1173C Carriers.

PubMed

Yang, Mina; Choi, Rihwa; Kim, June Soo; On, Young Keun; Bang, Oh Young; Cho, Hyun-Jung; Lee, Soo-Youn

2016-12-01

The purpose of this study was to evaluate the performance of 16 previously published warfarin dosing algorithms in Korean patients. The 16 algorithms were selected through a literature search and evaluated using a cohort of 310 Korean patients with atrial fibrillation or cerebral infarction who were receiving warfarin therapy. A large interindividual variation (up to 11-fold) in warfarin dose was observed (median, 25 mg/wk; range, 7-77 mg/wk). Estimated dose and actual maintenance dose correlated well overall (r range, 0.52-0.73). Mean absolute error (MAE) of the 16 algorithms ranged from -1.2 to -20.1 mg/wk. The percentage of patients whose estimated dose fell within 20% of the actual dose ranged from 1.0% to 49%. All algorithms showed poor accuracy with increased MAE in a higher dose range. Performance of the dosing algorithms was worse in patients with VKORC1 1173TC or CC than in total (r range, 0.38-0.61 vs 0.52-0.73; MAE range, -2.6 to -28.0 mg/wk vs -1.2 to -20.1 mg/wk). The algorithms had comparable prediction abilities but showed limited accuracy depending on ethnicity, warfarin dose, and VKORC1 genotype. Further studies are needed to develop genotype-guided warfarin dosing algorithms with greater accuracy in the Korean population. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Intergroup variation in robbing and bartering by long-tailed macaques at Uluwatu Temple (Bali, Indonesia).

PubMed

Brotcorne, Fany; Giraud, Gwennan; Gunst, Noëlle; Fuentes, Agustín; Wandia, I Nengah; Beudels-Jamar, Roseline C; Poncin, Pascal; Huynen, Marie-Claude; Leca, Jean-Baptiste

2017-10-01

Robbing and bartering (RB) is a behavioral practice anecdotally reported in free-ranging commensal macaques. It usually occurs in two steps: after taking inedible objects (e.g., glasses) from humans, the macaques appear to use them as tokens, returning them to humans in exchange for food. While extensively studied in captivity, our research is the first to investigate the object/food exchange between humans and primates in a natural setting. During a 4-month study in 2010, we used both focal and event sampling to record 201 RB events in a population of long-tailed macaques (Macaca fascicularis), including four neighboring groups ranging freely around Uluwatu Temple, Bali (Indonesia). In each group, we documented the RB frequency, prevalence and outcome, and tested the underpinning anthropogenic and demographic determinants. In line with the environmental opportunity hypothesis, we found a positive qualitative relation at the group level between time spent in tourist zones and RB frequency or prevalence. For two of the four groups, RB events were significantly more frequent when humans were more present in the environment. We also found qualitative partial support for the male-biased sex ratio hypothesis [i.e., RB was more frequent and prevalent in groups with higher ratios of (sub)adult males], whereas the group density hypothesis was not supported. This preliminary study showed that RB is a spontaneous, customary (in some groups), and enduring population-specific practice characterized by intergroup variation in Balinese macaques. As such, RB is a candidate for a new behavioral tradition in this species.

Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys

PubMed Central

Grant, Kathleen A.; Helms, Christa M.; Rogers, Laura S.M.; Purdy, Robert H.

2008-01-01

Positive modulation of GABAA and antagonism of NMDA receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol suggesting that these steroids may modulate ethanol addiction. The 4 isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (progesterone) [allopregnanolone (3α,5α-P), pregnanolone (3α,5β-P), epiallopregnanolone (3β,5α-P), epipregnanolone (3β,5β-P)], a synthetic analogue of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3α,5β-P HS)], and a structurally-similar, adrenally-derived steroid [3α-hydroxy-5-androstan-17-one (3α,5α-A, androsterone)], were assessed for ethanol-like discriminative stimulus effects 30 or 60 min after administration in male (n=9) and female (n=8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) with a 30-min pre-treatment interval. The 3α-hydroxysteroids completely substituted for ethanol (80% of cases) whereas the 3β-hydroxysteroids and 3α,5β-P HS rarely substituted for ethanol (6% of cases). There were no sex differences. Compared to monkeys trained to discriminate 2.0 g/kg ethanol, 3α,5β-P and 3α,5α-A substituted more potently in monkeys trained to discriminate 1.0 g/kg ethanol. Compared to the 5β-reduced isomer (3α,5β-P), the 5α isomer of pregnanolone (3α,5α-P) substituted for ethanol with 3–40-fold greater potency but was least efficacious in female monkeys trained to discriminate 2.0 g/kg ethanol. The data suggest that the discriminative stimulus effects of lower doses (1.0 g/kg) of ethanol are mediated to a greater extent by 3α,5β-P-and 3α,5α-A-sensitive receptors compared to higher doses (2.0 g/kg). Furthermore, the discriminative stimulus effects of ethanol appear to be mediated by activity at binding sites that are particularly sensitive to 3α,5α-P. PMID:18436788

Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys.

PubMed

Grant, Kathleen A; Helms, Christa M; Rogers, Laura S M; Purdy, Robert H

2008-07-01

Positive modulation of GABA(A) and antagonism of N-methyl-D-aspartate receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol, suggesting that these steroids may modulate ethanol addiction. The four isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (progesterone) [allopregnanolone (3alpha,5alpha-P), pregnanolone (3alpha,5beta-P), epiallopregnanolone (3beta,5alpha-P), and epipregnanolone (3beta,5beta-P)], a synthetic analog of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3alpha,5beta-P HS)], and a structurally similar, adrenally derived steroid [3alpha-hydroxy-5-androstan-17-one (3alpha,5alpha-A, androsterone)] were assessed for ethanol-like discriminative stimulus effects at 30 or 60 min after administration in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) with a 30-min pretreatment interval. The 3alpha-hydroxysteroids completely substituted for ethanol (80% of cases), whereas the 3beta-hydroxysteroids and 3alpha,5beta-P HS rarely substituted for ethanol (6% of cases). There were no sex differences. Compared with monkeys trained to discriminate 2.0 g/kg ethanol, 3alpha,5beta-P and 3alpha,5alpha-A substituted more potently in monkeys trained to discriminate 1.0 g/kg ethanol. Compared with the 5beta-reduced isomer (3alpha,5beta-P), the 5alpha isomer of pregnanolone (3alpha,5alpha-P) substituted for ethanol with 3 to 40-fold greater potency but was least efficacious in female monkeys trained to discriminate 2.0 g/kg ethanol. The data suggest that the discriminative stimulus effects of lower doses (1.0 g/kg) of ethanol are mediated to a greater extent by 3alpha,5beta-P- and 3alpha,5alpha-A-sensitive receptors compared with higher doses (2.0 g/kg). Furthermore, the discriminative stimulus effects of ethanol appear to be mediated by activity at binding sites that are particularly sensitive to 3alpha,5alpha-P.

Validation of multi-detector computed tomography as a non-invasive method for measuring ovarian volume in macaques (Macaca fascicularis).

PubMed

Jones, Jeryl C; Appt, Susan E; Werre, Stephen R; Tan, Joshua C; Kaplan, Jay R

2010-06-01

The purpose of this study was to validate low radiation dose, contrast-enhanced, multi-detector computed tomography (MDCT) as a non-invasive method for measuring ovarian volume in macaques. Computed tomography scans of four known-volume phantoms and nine mature female cynomolgus macaques were acquired using a previously described, low radiation dose scanning protocol, intravenous contrast enhancement, and a 32-slice MDCT scanner. Immediately following MDCT, ovaries were surgically removed and the ovarian weights were measured. The ovarian volumes were determined using water displacement. A veterinary radiologist who was unaware of actual volumes measured ovarian CT volumes three times, using a laptop computer, pen display tablet, hand-traced regions of interest, and free image analysis software. A statistician selected and performed all tests comparing the actual and CT data. Ovaries were successfully located in all MDCT scans. The iliac arteries and veins, uterus, fallopian tubes, cervix, ureters, urinary bladder, rectum, and colon were also consistently visualized. Large antral follicles were detected in six ovaries. Phantom mean CT volume was 0.702+/-SD 0.504 cc and the mean actual volume was 0.743+/-SD 0.526 cc. Ovary mean CT volume was 0.258+/-SD 0.159 cc and mean water displacement volume was 0.257+/-SD 0.145 cc. For phantoms, the mean coefficient of variation for CT volumes was 2.5%. For ovaries, the least squares mean coefficient of variation for CT volumes was 5.4%. The ovarian CT volume was significantly associated with actual ovarian volume (ICC coefficient 0.79, regression coefficient 0.5, P=0.0006) and the actual ovarian weight (ICC coefficient 0.62, regression coefficient 0.6, P=0.015). There was no association between the CT volume accuracy and mean ovarian CT density (degree of intravenous contrast enhancement), and there was no proportional or fixed bias in the CT volume measurements. Findings from this study indicate that MDCT is a valid non-invasive technique for measuring the ovarian volume in macaques.

Retinoid metabolism and transplacental pharmacokinetics in the cynomolgus monkey following a nonteratogenic dosing regimen with all-trans-retinoic acid.

PubMed

Tzimas, G; Nau, H; Hendrickx, A G; Peterson, P E; Hummler, H

1996-11-01

Retinoids often exhibit a complex metabolic pattern and differential transplacental kinetics, which make it difficult to pinpoint the proximate compound responsible for the observed teratogenic effect. We have therefore studied the pharmacokinetics and metabolism of all-trans-retinoic acid (all-trans-RA) in cynomolgus monkeys following application of a nonteratogenic dosing regimen and compared the results with corresponding data from a previous study with a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193]. All-trans-RA was administered to pregnant cynomolgus monkeys (Macaca fascicularis) by nasogastric intubation at a dose of 5 mg/kg body wt once daily from gestational day (GD) 16 to 26 and twice daily at 8-h intervals from GD 27 to 31. Examination of the fetuses of four dams on GD 100 +/- 2 showed no embryotoxic or teratogenic effects of the applied dosing regimen (Experiment 1). Maternal plasma retinoid pharmacokinetics on GD 16, 26, and 31 as well as embryonic retinoid profiles after the last drug administration on GD 31 were determined in thirteen further dams (Experiment 2). All-trans-RA reached much lower plasma concentrations after the last two treatments on GD 31 than after the first one on GD 16 and the eleventh one on GD 26 (0-24-h area-under-the-concentration-time-curve (AUC) values: 104 +/- 59 ng x h/ml (after the last treatment on GD 31), 189 +/- 110 (GD 16) and 393 +/- 305 ng x h/ml (GD 26). The predominant plasma metabolites of all-trans-RA were its beta-glucuronide and the beta-glucuronide of all-trans-4-oxo-RA. Both of these retinoids accumulated in the plasma during the period of treatment and displayed AUC values 5- to 30-fold higher than those of all-trans-RA. Embryonic concentrations of all-trans-RA were not increased over endogenous levels after the last administration on GD 31 when plasma concentrations were low. To evaluate the placental transport of all-trans-RA in the presence of high plasma concentrations, a further experiment was performed, in which a single dose of all-trans-RA (10 mg/kg body wt) was given to four pregnant monkeys on GD 31, and plasma pharmacokinetics as well as embryonic concentrations of retinoids at 4 h post-treatment were determined (Experiment 3). This dosing schedule yielded high plasma concentrations of all-trans-RA, while embryonic concentrations were about 40% of plasma levels. Based on the plasma AUC values on GDs 16 and 26 obtained in Experiment 2 and the degree of placental transfer, as determined on GD 31 in the presence of high plasma levels in Experiment 3, we estimated embryonic AUC values for the 24-h period following the nonteratogenic doses on GDs 16 and 26 in Experiment 2. These AUC values were similarly high to the embryonic AUC value of all-trans-RA obtained after application of the teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193]. In addition, plasma AUC values of all-trans-RA were 2- to 7-fold higher after all-trans-RA administration (present study) than after dosing with the teratogenic dose of 13-cis-RA. These results strengthen our recent suggestion that the teratogenic effects induced in cynomolgus monkeys by 13-cis-RA treatment cannot solely result from the action of all-trans-RA, but may involve 13-cis-RA and 13-cis-4-oxo-RA, which could act directly or function as transport vehicle.

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.

PubMed

Taylor, Carolyn W; Wang, Zhe; Macaulay, Elizabeth; Jagsi, Reshma; Duane, Frances; Darby, Sarah C

2015-11-15

Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this "mean heart dose." In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose. Copyright © 2015 Elsevier Inc. All rights reserved.

Antiviral efficacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques.

PubMed

Guedj, Jérémie; Piorkowski, Géraldine; Jacquot, Frédéric; Madelain, Vincent; Nguyen, Thi Huyen Tram; Rodallec, Anne; Gunther, Stephan; Carbonnelle, Caroline; Mentré, France; Raoul, Hervé; de Lamballerie, Xavier

2018-03-01

Despite repeated outbreaks, in particular the devastating 2014-2016 epidemic, there is no effective treatment validated for patients with Ebola virus disease (EVD). Among the drug candidates is the broad-spectrum polymerase inhibitor favipiravir, which showed a good tolerance profile in patients with EVD (JIKI trial) but did not demonstrate a strong antiviral efficacy. In order to gain new insights into the antiviral efficacy of favipiravir and improve preparedness and public health management of future outbreaks, we assess the efficacy achieved by ascending doses of favipiravir in Ebola-virus-infected nonhuman primates (NHPs). A total of 26 animals (Macaca fascicularis) were challenged intramuscularly at day 0 with 1,000 focus-forming units of Ebola virus Gabon 2001 strain and followed for 21 days (study termination). This included 13 animals left untreated and 13 treated with doses of 100, 150, and 180 mg/kg (N = 3, 5, and 5, respectively) favipiravir administered intravenously twice a day for 14 days, starting 2 days before infection. All animals left untreated or treated with 100 mg/kg died within 10 days post-infection, while animals receiving 150 and 180 mg/kg had extended survival (P < 0.001 and 0.001, respectively, compared to untreated animals), leading to a survival rate of 40% (2/5) and 60% (3/5), respectively, at day 21. Favipiravir inhibited viral replication (molecular and infectious viral loads) in a drug-concentration-dependent manner (P values < 0.001), and genomic deep sequencing analyses showed an increase in virus mutagenesis over time. These results allowed us to identify that plasma trough favipiravir concentrations greater than 70-80 μg/ml were associated with reduced viral loads, lower virus infectivity, and extended survival. These levels are higher than those found in the JIKI trial, where patients had median trough drug concentrations equal to 46 and 26 μg/ml at day 2 and day 4 post-treatment, respectively, and suggest that the dosing regimen in the JIKI trial was suboptimal. The environment of a biosafety level 4 laboratory introduces a number of limitations, in particular the difficulty of conducting blind studies and performing detailed pharmacological assessments. Further, the extrapolation of the results to patients with EVD is limited by the fact that the model is fully lethal and that treatment initiation in patients with EVD is most often initiated several days after infection, when symptoms and high levels of viral replication are already present. Our results suggest that favipiravir may be an effective antiviral drug against Ebola virus that relies on RNA chain termination and possibly error catastrophe. These results, together with previous data collected on tolerance and pharmacokinetics in both NHPs and humans, support a potential role for high doses of favipiravir for future human interventions.

Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India.

PubMed

Velankar, Avadhoot D; Kumara, Honnavalli N; Pal, Arijit; Mishra, Partha Sarathi; Singh, Mewa

2016-01-01

Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species.

The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

PubMed

Lim, Khai Lone; Amir, Amirah; Lau, Yee Ling; Fong, Mun Yik

2017-08-11

The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated. The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes. Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P < 0.0001). However, no difference in binding activity level was seen in the binding assay using M. fascicularis erythrocytes. This study is the first report of phenotypic difference between PkDBPαII haplotypes. The biological implication of this finding is yet to be determined. Therefore, further studies need to be carried out to determine whether this differential binding level can be associated with severity of knowlesi malaria in human.

The trade balance of grooming and its coordination of reciprocation and tolerance in Indonesian long-tailed macaques (Macaca fascicularis).

PubMed

Gumert, Michael D; Ho, Moon-Ho R

2008-07-01

We collected data on grooming, proximity, and aggression in long-tailed macaques (Macaca fascicularis) in Kalimantan, Indonesia. We used this data to study how grooming influenced a receiver's (B) behavior towards the bout's initiator (A). In our first analysis, post-grooming samples were collected after A groomed B. These were compared to matched-control samples of similar conditions but A had not previously groomed B. This comparison was performed on 26 individuals (16 female, 3 male, 7 immature) and tested whether A's initial act of grooming increased the pair's time in proximity and the amount of time B groomed A. We also tested if A's grooming decreased B's aggression towards A per time in proximity. Rates of B-->A aggression per time in proximity with A for 39 individuals (18 female, 5 male, 16 immature) were compared between post-grooming and focal sample data. Finally, we studied 248 grooming bouts to test if the first two grooming episodes were time matched. We assessed the influence of age, sex, rank and inferred kinship on time matching, and controlled for individual variation and tendency to groom using a general linear mixed model. Our results showed that A-->B grooming acted to increase B-->A grooming and the pair's proximity, while lowering B-->A aggression. Despite these effects, episodes in grooming bouts were generally not matched, except weakly among similar partners (i.e., female pairs and immature pairs). Grooming imbalance was greatest across age-sex class (i.e., male-female and adult-immature pairs). In similar pairs, grooming duration was skewed in favor of high-ranking individuals. We conclude grooming established tolerance and increased the likelihood that grooming reciprocation would occur, but grooming durations were not typically matched within bouts. Lack of time matching may be the result of grooming that is performed to coordinate interchanges of other social services.

There Is More than One Way to Crack an Oyster: Identifying Variation in Burmese Long-Tailed Macaque (Macaca fascicularis aurea) Stone-Tool Use

PubMed Central

Tan, Amanda; Tan, Say Hoon; Vyas, Dhaval; Malaivijitnond, Suchinda; Gumert, Michael D.

2015-01-01

We explored variation in patterns of percussive stone-tool use on coastal foods by Burmese long-tailed macaques (Macaca fascicularis aurea) from two islands in Laem Son National Park, Ranong, Thailand. We catalogued variation into three hammering classes and 17 action patterns, after examining 638 tool-use bouts across 90 individuals. Hammering class was based on the stone surface used for striking food, being face, point, and edge hammering. Action patterns were discriminated by tool material, hand use, posture, and striking motion. Hammering class was analyzed for associations with material and behavioural elements of tool use. Action patterns were not, owing to insufficient instances of most patterns. We collected 3077 scan samples from 109 macaques on Piak Nam Yai Island’s coasts, to determine the proportion of individuals using each hammering class and action pattern. Point hammering was significantly more associated with sessile foods, smaller tools, faster striking rates, smoother recoil, unimanual use, and more varied striking direction, than were face and edge hammering, while both point and edge hammering were significantly more associated with precision gripping than face hammering. Edge hammering also showed distinct differences depending on whether such hammering was applied to sessile or unattached foods, resembling point hammering for sessile foods and face hammering for unattached foods. Point hammering and sessile edge hammering compared to prior descriptions of axe hammering, while face and unattached edge hammering compared to pound hammering. Analysis of scans showed that 80% of individuals used tools, each employing one to four different action patterns. The most common patterns were unimanual point hammering (58%), symmetrical-bimanual face hammering (47%) and unimanual face hammering (37%). Unimanual edge hammering was relatively frequent (13%), compared to the other thirteen rare action patterns (<5%). We compare our study to other stone-using primates, and discuss implications for further research. PMID:25970286

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study.

PubMed

Fitton, L C; Shi, J F; Fagan, M J; O'Higgins, P

2012-07-01

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the error in applied muscle forces is best judged against the magnitude of the effect that is being investigated. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Use of photogrammetry as a means to assess hybrids of rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques.

PubMed

Jadejaroen, Janya; Hamada, Yuzuru; Kawamoto, Yoshi; Malaivijitnond, Suchinda

2015-01-01

Rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques are the most commonly used non-human primate models for biomedical research, but it is difficult to identify these two species in the hybrid zone (15-20°N). In this work, we used morphological values obtained via photogrammetry to assess hybrids of rhesus and long-tailed macaques at Khao Khieow Open Zoo (KKZ; 13°21'N, 101°06'E), eastern Thailand. Long-tailed and rhesus macaques have species-specific tail lengths and contrasts of their yellowish pelages. The accuracy and precision of the relative tail length (%RTL) and the contrast of the yellow hue (Cb*) of the pelage, as obtained from photographs, were compared with the corresponding direct measurements (morphometrics). The photogrammetric and morphometric measurements of %RTL and Cb* were highly significantly correlated (r = 0.989 and 0.980, p < 0.001), and there were no significant differences between the two datasets (t test, p = 0.13 and 0.41; n = 42 and 17 for %RTL and Cb*, respectively). The reproducibilities of the %RTL and Cb* measurements (calculated in the photogrammetric case by taking photographs of the same macaques in two different environments) were significantly correlated between the datasets (r = 0.983 and 0.914, p < 0.001 and 0.005), and there were no significant differences between the datasets (t test, p = 0.539 and 0.344; n = 30 each for %RTL and Cb*, respectively). The %RTL and Cb* data were combined with data on the crown and cheek hair patterns and sex skin reddening of the macaques, and this combined data set was then analyzed by multiple correspondence analysis and agglomerative hierarchical cluster analysis, leading to the categorization of the rhesus macaques, long-tailed macaques, and hybrids at KKZ into five groups. Thus, photogrammetry can be utilized to identify macaque species or hybrids when species identification relies mainly on tail length and pelage color.

Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study

PubMed Central

Fitton, L C; Shi, J F; Fagan, M J; O’Higgins, P

2012-01-01

Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the error in applied muscle forces is best judged against the magnitude of the effect that is being investigated. PMID:22690885

Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India

PubMed Central

Velankar, Avadhoot D.; Kumara, Honnavalli N.

2016-01-01

Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species. PMID:26886197

Seed dormancy and germination vary within and among species of milkweeds

PubMed Central

Kaye, Thomas N; Sandlin, Isaac J; Bahm, Matt A

2018-01-01

Abstract Pollinators in general and monarch butterflies in particular are in decline due to habitat loss. Efforts to restore habitats for insects that rely on specific plant groups as larvae or adults depend on the ability of practitioners to grow and produce these plants. Monarch larvae feed exclusively on milkweed species, primarily in the genus Asclepias, making propagation and restoration of these plants crucial for habitat restoration. Seed germination protocols for milkweeds are not well established, in part due to the large number of milkweed species and conflicting reports of seed dormancy in the genus. We tested for seed dormancy and the optimum period of cold stratification in 15 populations of A. speciosa and 1–2 populations of five additional species, including A. asperula, A. fascicularis, A. subulata, A. subverticillata and A. syriaca. We exposed seeds to cold (5 °C) moist conditions for 0, 2, 4, 6 and 8 weeks and then moved them to 15 °C/25 °C alternating temperatures. In A. speciosa, dormancy was detected in eight populations, and this dormancy was broken by 2–4 weeks of cold stratification. The remaining seven populations showed no dormancy. Seed dormancy was also detected in two populations of A. fascicularis (broken by 4–6 weeks of cold stratification) and a single population of A. syriaca (broken by 2 weeks of cold stratification). No dormancy was detected in A. asperula, A. subulata or A. subverticillata. Seed dormancy appears to be widespread in the genus (confirmed in 15 species) but can vary between populations even within the same species. Variation in seed dormancy and cold stratification requirements within and among Asclepias species suggests local adaptation and maternal environments may drive seedling ecology, and that growers should watch for low germination and use cold stratification as needed to maximize seed germination and retain genetic variability in restored populations. PMID:29593856

SU-F-T-194: Analyzing the Effect of Range Shifter Air Gap On TPS Dose Modeling Accuracy in Superficial PBS Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirey, R; Wu, H

2016-06-15

Purpose: Treatment planning systems (TPS) may not accurately model superficial dose distributions of range shifted proton pencil beam scanning (PBS) treatments. Numerous patient-specific QA tests performed on superficially treated PBS plans have shown a consistent overestimate of dose by the TPS. This study quantifies variations between TPS planned dose and measured dose as a function of range shifter air gap and treatment depths up to 5 cm. Methods: PBS treatment plans were created in the TPS to uniformly irradiate a volume of solid water. One plan was created for each range shifter position analyzed, and all plans utilized identical dosemore » optimization parameters. Each optimized plan was analyzed in the TPS to determine the planned dose at varying depths. A PBS proton therapy system with a 3.5 cm lucite range shifter delivered the treatment plans, and a parallel plate chamber embedded in RW3 solid water measured dose at shallow depths for each air gap. Differences between measured and planned doses were plotted and analyzed. Results: The data show that the TPS more accurately models superficial dose as the air gap between the range shifter and patient surface decreases. Air gaps less than 10 cm have an average dose difference of only 1.6%, whereas air gaps between 10 and 20 cm differ by 3.0% and gaps greater than 20 cm differ by 4.4%. Conclusion: This study has shown that the TPS is unable to accurately model superficial dose with a large range shifter air gap. Dose differences greater than 3% will likely cause QA failure, as many institutions analyze patient QA with a 3%/3mm gamma analysis. For superficial PBS therapy, range shifter positions should be chosen to keep the air gap less then 10 cm when patient setup and gantry geometry allow.« less

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viel, Francis; Duzenli, Cheryl; British Columbia Cancer Agency, Department of Medical Physics, Vancouver Centre

2014-08-15

Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data andmore » a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.« less

Reduction of the unnecessary dose from the over-range area with a spiral dynamic z-collimator: comparison of beam pitch and detector coverage with 128-detector row CT.

PubMed

Shirasaka, Takashi; Funama, Yoshinori; Hayashi, Mutsukazu; Awamoto, Shinichi; Kondo, Masatoshi; Nakamura, Yasuhiko; Hatakenaka, Masamitsu; Honda, Hiroshi

2012-01-01

Our purpose in this study was to assess the radiation dose reduction and the actual exposed scan length of over-range areas using a spiral dynamic z-collimator at different beam pitches and detector coverage. Using glass rod dosimeters, we measured the unilateral over-range scan dose between the beginning of the planned scan range and the beginning of the actual exposed scan range. Scanning was performed at detector coverage of 80.0 and 40.0 mm, with and without the spiral dynamic z-collimator. The dose-saving ratio was calculated as the ratio of the unnecessary over-range dose, with and without the spiral dynamic z-collimator. In 80.0 mm detector coverage without the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 108, 120, and 126 mm, corresponding to a beam pitch of 0.60, 0.80, and 0.99, respectively. With the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 48, 66, and 84 mm with a beam pitch of 0.60, 0.80, and 0.99, respectively. The dose-saving ratios with and without the spiral dynamic z-collimator for a beam pitch of 0.60, 0.80, and 0.99 were 35.07, 24.76, and 13.51%, respectively. With 40.0 mm detector coverage, the dose-saving ratios with and without the spiral dynamic z-collimator had the highest value of 27.23% with a low beam pitch of 0.60. The spiral dynamic z-collimator is important for a reduction in the unnecessary over-range dose and makes it possible to reduce the unnecessary dose by means of a lower beam pitch.

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Carolyn W., E-mail: carolyn.taylor@ctsu.ox.ac.uk; Wang, Zhe; Macaulay, Elizabeth

Purpose: Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Methods and Materials: Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this “mean heart dose.” Results: In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28more » countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Conclusions: Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose.« less

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

2016-06-01

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

Pulmonary cestodiasis in a cynomolgus monkey (Macaca fascicularis).

PubMed

Guillot, L M; Green, L C

1992-04-01

Cestodiasis in primates has been noted historically to occur quite frequently, although tissue damage and clinical signs may or may not be apparent. Larval cestodes, such as hydatid cysts or cysticercus cysts, are known to cause extensive tissue damage, while other larval cestodes, such as tetrathyridia, cause minimal damage to the host. This case history concerns an apparently healthy cynomolgus monkey that was part of a surgical study. During the study, all parameters were normal. The monkey died 3 hours postsurgery. The apparent cause of death was respiratory arrest. At necropsy, it was discovered there were 1- to 3-mm-diameter cysts, which on transection extruded 2- to 5-mm-long larvae. The larvae could not be positively identified; however, they resembled tetrathyridia of Mesocestoides sp.

Using stereotactic brain atlases for small rodents and nonhuman primates for optrode array customization

NASA Astrophysics Data System (ADS)

Boutte, Ronald W.; Merlin, Sam; Griffiths, Brandon; Parry, Trent; Blair, Steve

2017-02-01

As the optogenetic field expands its need to target with high specificity only grows more crucial. This work will show a method for customizing soda-lime glass optrode arrays so that fine structures within the brains of small rodents and nonhuman primates can be optically interrogated below the outer cortical layer. An 8 × 6 array is customized for optrode length (400 μm ), optrode width (75 μm ), optrode pitch (400 μm ), backplane thickness (500 μm ), and overall form factor (3.45 mm × 2.65 mm ). The 400 μm long optrode is capable of illuminating the cortical Layer IV of rhesus macaque ( Macaca Fascicularis ) and the motor cortex of small mice ( Mus Musculus ).

Quantifying the effect of air gap, depth, and range shifter thickness on TPS dosimetric accuracy in superficial PBS proton therapy.

PubMed

Shirey, Robert J; Wu, Hsinshun Terry

2018-01-01

This study quantifies the dosimetric accuracy of a commercial treatment planning system as functions of treatment depth, air gap, and range shifter thickness for superficial pencil beam scanning proton therapy treatments. The RayStation 6 pencil beam and Monte Carlo dose engines were each used to calculate the dose distributions for a single treatment plan with varying range shifter air gaps. Central axis dose values extracted from each of the calculated plans were compared to dose values measured with a calibrated PTW Markus chamber at various depths in RW3 solid water. Dose was measured at 12 depths, ranging from the surface to 5 cm, for each of the 18 different air gaps, which ranged from 0.5 to 28 cm. TPS dosimetric accuracy, defined as the ratio of calculated dose relative to the measured dose, was plotted as functions of depth and air gap for the pencil beam and Monte Carlo dose algorithms. The accuracy of the TPS pencil beam dose algorithm was found to be clinically unacceptable at depths shallower than 3 cm with air gaps wider than 10 cm, and increased range shifter thickness only added to the dosimetric inaccuracy of the pencil beam algorithm. Each configuration calculated with Monte Carlo was determined to be clinically acceptable. Further comparisons of the Monte Carlo dose algorithm to the measured spread-out Bragg Peaks of multiple fields used during machine commissioning verified the dosimetric accuracy of Monte Carlo in a variety of beam energies and field sizes. Discrepancies between measured and TPS calculated dose values can mainly be attributed to the ability (or lack thereof) of the TPS pencil beam dose algorithm to properly model secondary proton scatter generated in the range shifter. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

PubMed

Limoges, D; Dieterich, H A; Yeh, C-M; Vaidyanathan, S; Howard, D; Dole, W P

2008-05-01

To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model

PubMed Central

2011-01-01

Background Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. Methods We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. Results Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. Conclusions The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child. PMID:21635774

Standardized Full-Field Electroretinography in the Green Monkey (Chlorocebus sabaeus)

PubMed Central

Bouskila, Joseph; Javadi, Pasha; Palmour, Roberta M.; Bouchard, Jean-François; Ptito, Maurice

2014-01-01

Abstract Full-field electroretinography is an objective measure of retinal function, serving as an important diagnostic clinical tool in ophthalmology for evaluating the integrity of the retina. Given the similarity between the anatomy and physiology of the human and Green Monkey eyes, this species has increasingly become a favorable non-human primate model for assessing ocular defects in humans. To test this model, we obtained full-field electroretinographic recordings (ERG) and normal values for standard responses required by the International Society for Clinical Electrophysiology of Vision (ISCEV). Photopic and scotopic ERG recordings were obtained by full-field stimulation over a range of 6 log units of intensity in dark-adapted or light-adapted eyes of adult Green Monkeys (Chlorocebus sabaeus). Intensity, duration, and interval of light stimuli were varied separately. Reproducible values of amplitude and latency were obtained for the a- and b-waves, under well-controlled adaptation and stimulus conditions; the i-wave was also easily identifiable and separated from the a-b-wave complex in the photopic ERG. The recordings obtained in the healthy Green Monkey matched very well with those in humans and other non-human primate species (Macaca mulatta and Macaca fascicularis). These results validate the Green Monkey as an excellent non-human primate model, with potential to serve for testing retinal function following various manipulations such as visual deprivation or drug evaluation. PMID:25360686

An Automated Motion Detection and Reward System for Animal Training.

PubMed

Miller, Brad; Lim, Audrey N; Heidbreder, Arnold F; Black, Kevin J

2015-12-04

A variety of approaches has been used to minimize head movement during functional brain imaging studies in awake laboratory animals. Many laboratories expend substantial effort and time training animals to remain essentially motionless during such studies. We could not locate an "off-the-shelf" automated training system that suited our needs.  We developed a time- and labor-saving automated system to train animals to hold still for extended periods of time. The system uses a personal computer and modest external hardware to provide stimulus cues, monitor movement using commercial video surveillance components, and dispense rewards. A custom computer program automatically increases the motionless duration required for rewards based on performance during the training session but allows changes during sessions. This system was used to train cynomolgus monkeys (Macaca fascicularis) for awake neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The automated system saved the trainer substantial time, presented stimuli and rewards in a highly consistent manner, and automatically documented training sessions. We have limited data to prove the training system's success, drawn from the automated records during training sessions, but we believe others may find it useful. The system can be adapted to a range of behavioral training/recording activities for research or commercial applications, and the software is freely available for non-commercial use.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucconi, G; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Bentefour, E

Purpose: The clinical commissioning of a workflow for pre-treatment range verification/adjustment for the head treatment of pediatric medulloblastoma patients, including dose monitoring during treatment. Methods: An array of Si-diodes (DIODES Incorporated) is placed on the patient skin on the opposite side to the beam entrance. A “scout” SOBP beam, with a longer beam range to cover the diodes in its plateau, is delivered; the measured signal is analyzed and the extracted water equivalent path lengths (WEPL) are compared to the expected values, revealing if a range correction is needed. Diodes stay in place during treatment to measure dose. The workflowmore » was tested in solid water and head phantoms and validated against independent WEPL measurements. Both measured WEPL and skin doses were compared to computed values from the TPS (XiO); a Markus chamber was used for reference dose measurements. Results: The WEPL accuracy of the method was verified by comparing it with the dose extinction method. It resulted, for both solid water and head phantom, in the sub-millimeter range, with a deviation less than 1% to the value extracted from the TPS. The accuracy of dose measurements in the fall-off part of the dose profile was validated against the Markus chamber. The entire range verification workflow was successfully tested for the mock-treatment of head phantom with the standard delivery of 90 cGy per field per fraction. The WEPL measurement revealed no need for range correction. The dose measurements agreed to better than 4% with the prescription dose. The robustness of the method and workflow, including detector array, hardware set and software functions, was successfully stress-tested with multiple repetitions. Conclusion: The performance of the in-vivo range verification system and related workflow meet the clinical requirements in terms of the needed WEPL accuracy for pretreatment range verification with acceptable dose to the patient.« less

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

PubMed

Elschot, Mattijs; Nijsen, Johannes F W; Lam, Marnix G E H; Smits, Maarten L J; Prince, Jip F; Viergever, Max A; van den Bosch, Maurice A A J; Zonnenberg, Bernard A; de Jong, Hugo W A M

2014-10-01

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

Cochlear Implant Electrode Array From Partial to Full Insertion in Non-Human Primate Model.

PubMed

Manrique-Huarte, Raquel; Calavia, Diego; Gallego, Maria Antonia; Manrique, Manuel

2018-04-01

To determine the feasibility of progressive insertion (two sequential surgeries: partial to full insertion) of an electrode array and to compare functional outcomes. 8 normal-hearing animals (Macaca fascicularis (MF)) were included. A 14 contact electrode array, which is suitably sized for the MF cochlea was partially inserted (PI) in 16 ears. After 3 months of follow-up revision surgery the electrode was advanced to a full insertion (FI) in 8 ears. Radiological examination and auditory testing was performed monthly for 6 months. In order to compare the values a two way repeated measures ANOVA was used. A p-value below 0.05 was considered as statistically significant. IBM SPSS Statistics V20 was used. Surgical procedure was completed in all cases with no complications. Mean auditory threshold shift (ABR click tones) after 6 months follow-up is 19 dB and 27 dB for PI and FI group. For frequencies 4, 6, 8, 12, and 16 kHz in the FI group, tone burst auditory thresholds increased after the revision surgery showing no recovery thereafter. Mean threshold shift at 6 months of follow- up is 19.8 dB ranging from 2 to 36dB for PI group and 33.14dB ranging from 8 to 48dB for FI group. Statistical analysis yields no significant differences between groups. It is feasible to perform a partial insertion of an electrode array and progress on a second surgical time to a full insertion (up to 270º). Hearing preservation is feasible for both procedures. Note that a minimal threshold deterioration is depicted among full insertion group, especially among high frequencies, with no statistical differences.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poplawski, L; Li, T; Chino, J

Purpose: In brachytherapy, structures surrounding the target have the potential to move between treatments and receive unknown dose. Deformable image registration could overcome challenges through dose accumulation. This study uses two possible deformable dose summation techniques and compares the results to point dose summation currently performed in clinic. Methods: Data for ten patients treated with a Syed template was imported into the MIM software (Cleveland, OH). The deformable registration was applied to structures by masking other image data to a single intensity. The registration flow consisted of the following steps: 1) mask CTs so that each of the structures-of-interest hadmore » one unique intensity; 2) perform applicator — based rigid registration; 3) Perform deformable registration; 4) Refine registration by changing local alignments manually; 5) Repeat steps 1 to 3 until desired structure adequately deformed; 5) Transfer each deformed contours to the first CT. The deformed structure accuracy was determined by a dice similarity coefficient (DSC) comparison with the first fraction. Two dose summation techniques were investigated: a deformation and recalculation on the structure; and a dose deformation and accumulation method. Point doses were used as a comparison value. Results: The Syed deformations have DSC ranging from 0.53 to 0.97 and 0.75 and 0.95 for the bladder and rectum, respectively. For the bladder, contour deformation addition ranged from −34.8% to 0.98% and dose deformation accumulation ranged from −35% to 29.3% difference from clinical calculations. For the rectum, contour deformation addition ranged from −5.2% to 16.9% and the dose deformation accumulation ranged from −29.1% to 15.3% change. Conclusion: Deforming dose for summation leads to different volumetric doses than when dose is recalculated on deformed structures, raising concerns about the accuracy of the deformed dose. DSC alone cannot be used to establish the accuracy of a deformation for brachy dose summation purpose.« less

TH-A-19A-06: Site-Specific Comparison of Analytical and Monte Carlo Based Dose Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuemann, J; Grassberger, C; Paganetti, H

2014-06-15

Purpose: To investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict dose distributions and to verify currently used uncertainty margins in proton therapy. Methods: Dose distributions predicted by an analytical pencilbeam algorithm were compared with Monte Carlo simulations (MCS) using TOPAS. 79 complete patient treatment plans were investigated for 7 disease sites (liver, prostate, breast, medulloblastoma spine and whole brain, lung and head and neck). A total of 508 individual passively scattered treatment fields were analyzed for field specific properties. Comparisons based on target coverage indices (EUD, D95, D90 and D50)more » were performed. Range differences were estimated for the distal position of the 90% dose level (R90) and the 50% dose level (R50). Two-dimensional distal dose surfaces were calculated and the root mean square differences (RMSD), average range difference (ARD) and average distal dose degradation (ADD), the distance between the distal position of the 80% and 20% dose levels (R80- R20), were analyzed. Results: We found target coverage indices calculated by TOPAS to generally be around 1–2% lower than predicted by the analytical algorithm. Differences in R90 predicted by TOPAS and the planning system can be larger than currently applied range margins in proton therapy for small regions distal to the target volume. We estimate new site-specific range margins (R90) for analytical dose calculations considering total range uncertainties and uncertainties from dose calculation alone based on the RMSD. Our results demonstrate that a reduction of currently used uncertainty margins is feasible for liver, prostate and whole brain fields even without introducing MC dose calculations. Conclusion: Analytical dose calculation algorithms predict dose distributions within clinical limits for more homogeneous patients sites (liver, prostate, whole brain). However, we recommend treatment plan verification using Monte Carlo simulations for patients with complex geometries.« less

SU-F-BRD-05: Robustness of Dose Painting by Numbers in Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montero, A Barragan; Sterpin, E; Lee, J

Purpose: Proton range uncertainties may cause important dose perturbations within the target volume, especially when steep dose gradients are present as in dose painting. The aim of this study is to assess the robustness against setup and range errors for high heterogeneous dose prescriptions (i.e., dose painting by numbers), delivered by proton pencil beam scanning. Methods: An automatic workflow, based on MATLAB functions, was implemented through scripting in RayStation (RaySearch Laboratories). It performs a gradient-based segmentation of the dose painting volume from 18FDG-PET images (GTVPET), and calculates the dose prescription as a linear function of the FDG-uptake value on eachmore » voxel. The workflow was applied to two patients with head and neck cancer. Robustness against setup and range errors of the conventional PTV margin strategy (prescription dilated by 2.5 mm) versus CTV-based (minimax) robust optimization (2.5 mm setup, 3% range error) was assessed by comparing the prescription with the planned dose for a set of error scenarios. Results: In order to ensure dose coverage above 95% of the prescribed dose in more than 95% of the GTVPET voxels while compensating for the uncertainties, the plans with a PTV generated a high overdose. For the nominal case, up to 35% of the GTVPET received doses 5% beyond prescription. For the worst of the evaluated error scenarios, the volume with 5% overdose increased to 50%. In contrast, for CTV-based plans this 5% overdose was present only in a small fraction of the GTVPET, which ranged from 7% in the nominal case to 15% in the worst of the evaluated scenarios. Conclusion: The use of a PTV leads to non-robust dose distributions with excessive overdose in the painted volume. In contrast, robust optimization yields robust dose distributions with limited overdose. RaySearch Laboratories is sincerely acknowledged for providing us with RayStation treatment planning system and for the support provided.« less

Characterization of a prototype strain of hepatitis E virus.

PubMed

Tsarev, S A; Emerson, S U; Reyes, G R; Tsareva, T S; Legters, L J; Malik, I A; Iqbal, M; Purcell, R H

1992-01-15

A strain of hepatitis E virus (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, was characterized extensively. Six cynomolgus monkeys (Macaca fascicularis) were infected with a strain of hepatitis E virus from Pakistan. Reverse transcription-polymerase chain reaction was used to determine the pattern of virus shedding in feces, bile, and serum relative to hepatitis and induction of specific antibodies. Virtually the entire genome of SAR-55 (7195 nucleotides) was sequenced. Comparison of the sequence of SAR-55 with that of a Burmese strain revealed a high level of homology except for one region encoding 100 amino acids of a putative nonstructural polyprotein. Identification of this region as hypervariable was obtained by partial sequencing of a third isolate of hepatitis E virus from Kirgizia.

Reemergence of Reston ebolavirus in Cynomolgus Monkeys, the Philippines, 2015.

PubMed

Demetria, Catalino; Smith, Ina; Tan, Titus; Villarico, Daniel; Simon, Edson Michael; Centeno, Rex; Tachedjian, Mary; Taniguchi, Satoshi; Shimojima, Masayuki; Miranda, Noel Lee J; Miranda, Mary Elizabeth; Rondina, Melissa Marie R; Capistrano, Rowena; Tandoc, Amado; Marsh, Glenn; Eagles, Debbie; Cruz, Ramses; Fukushi, Shuetsu

2018-07-01

In August 2015, a nonhuman primate facility south of Manila, the Philippines, noted unusual deaths of 6 cynomolgus monkeys (Macaca fascicularis), characterized by generalized rashes, inappetence, or sudden death. We identified Reston ebolavirus (RESTV) infection in monkeys by using serologic and molecular assays. We isolated viruses in tissues from infected monkeys and determined viral genome sequences. RESTV found in the 2015 outbreak is genetically closer to 1 of the 4 RESTVs that caused the 2008 outbreak among swine. Eight macaques, including 2 also infected with RESTV, tested positive for measles. Concurrently, the measles virus was circulating throughout the Philippines, indicating that the infection of the macaques may be a reverse zoonosis. Improved biosecurity measures will minimize the public health risk, as well as limit the introduction of disease and vectors.

The colonization of carrion by soldier fly, Ptecticus melanurus (Walker) (Diptera: Stratiomyidae) in a tropical forest in Malaysia: a new potential species for minimum PMI estimation.

PubMed

Azwandi, A; Omar, B

2012-12-01

This paper discusses the colonization of the stratiomyid species Ptecticus melanurus (Walker) (Diptera: Stratiomyidae) in monkey carrion and its potential for the determination of the minimum time since death (PMI). A study was conducted in a tropical forest at Bangi, Malaysia from 13 November 2009 to 8 June 2011. Twelve monkey carcasses (Macaca fascicularis Raffles) were used and divided in equal number into three different field trials. Adults of P. melanurus were first observed on monkey carrions on the second day the carcasses were placed in the field while their penultimate instar larvae were found in the wet soil under and beside carcass from day 8 to 31 days postmortem.

SU-F-T-587: Quality Assurance of Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) for Patient Specific Plans: A Comparison Between MATRIXX and Delta4 QA Devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, YC; Lu, SH; Chen, LH

2016-06-15

Purpose: Patient-specific quality assurance (QA) is necessary to accurately deliver high dose radiation to the target, especially for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). Unlike previous 2 dimensional (D) array QA devices, Delta{sup 4} can verify the dose delivery in 3D. In this study, the difference between calculated and measured dose distribution was compared with two QA devices (MATRIXX and Delta{sup 4}) to evaluate the delivery accuracy. Methods: Twenty-seven SRS/SBRT plans with VMAT were verified with point-dose and dose-map analysis. We use an ion chamber (A1SL, 0.053cc) for point-dose measurement. For verification of the dose map, themore » differences between the calculated and measured doses were analyzed with a gamma index using MATRIXX and Delta{sup 4} devices. The passing criteria for gamma evaluation were set at 3 mm for distance-to-agreement (DTA) and 3% for dose-difference. A gamma index less than 1 was defined as the verification passing the criteria and satisfying at least 95% of the points. Results: The mean prescribed dose and fraction was 40 ± 14.41 Gy (range: 16–60) and 10 ± 2.35 fractions (range: 1–8), respectively. In point dose analysis, the differences between the calculated and measured doses were all less than 5% (mean: 2.12 ± 1.13%; range: −0.55% to 4.45%). In dose-map analysis, the average passing rates were 99.38 ± 0.96% (range: 95.31–100%) and 100 ± 0.12% (range: 99.5%–100%) for MATRIXX and Delta{sup 4}, respectively. Even using criteria of 2%/2 mm, the passing rate of Delta{sup 4} was still more than 95% (mean: 99 ± 1.08%; range: 95.6%–100%). Conclusion: Both MATRIXX and Delta{sup 4} offer accurate and efficient verification for SRS/SBRT plans. The results measured by MATRIXX and Delta{sup 4} dosimetry systems are similar for SRS/SBRT performed with the VMAT technique.« less

Alternative chitosan-based EPR dosimeter applicable for a relatively wide range of gamma radiation doses

NASA Astrophysics Data System (ADS)

Piroonpan, Thananchai; Katemake, Pichayada; Panritdam, Eagkapong; Pasanphan, Wanvimol

2017-12-01

Chitosan biopolymer is proposed as an alternative EPR dosimeter. Its ability to be EPR dosimeter was studied in comparison with the conventional alanine, sugars (i.e., glucose and sucrose), formate derivatives (i.e., lithium (Li), magnesium (Mg), and calcium (Ca) formate). Ethylene vinyl acetate (EVA) and paraffin were used as binder for the preparation of composite EPR dosimeter. Dose responses of all materials were investigated in a wide dose range of radiation doses, i.e., low-level (0-1 kGy), medium-level (1-10 kGy) and high-level (10-100 kGy). The EPR dosimeter properties were studied under different parameters, i.e., microwave power, materials contents, absorbed doses, storage conditions and post-irradiation effects. Li-formate showed a simple EPR spectrum and exhibited superior radiation response for low-dose range; whereas chitosan and sucrose exhibited linear dose response in all studied dose ranges. The EPR signals of chitosan exhibited similar stability as glucose, Li-formate and alanine at ambient temperature after irradiation as long as a year. All EPR signals of the studied materials were affected post-irradiation temperature and humidity after gamma irradiation. The EPR signal of chitosan exhibited long-term stability and it was not sensitive to high storage temperatures and humidity values after irradiation. Chitosan has a good merit as the alternative bio-based material for a stable EPR dosimeter in a wide range of radiation-absorbed doses.

SU-F-I-33: Estimating Radiation Dose in Abdominal Fat Quantitative CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X; Yang, K; Liu, B

Purpose: To compare size-specific dose estimate (SSDE) in abdominal fat quantitative CT with another dose estimate D{sub size,L} that also takes into account scan length. Methods: This study complied with the requirements of the Health Insurance Portability and Accountability Act. At our institution, abdominal fat CT is performed with scan length = 1 cm and CTDI{sub vol} = 4.66 mGy (referenced to body CTDI phantom). A previously developed CT simulation program was used to simulate single rotation axial scans of 6–55 cm diameter water cylinders, and dose integral of the longitudinal dose profile over the central 1 cm length wasmore » used to predict the dose at the center of one-cm scan range. SSDE and D{sub size,L} were assessed for 182 consecutive abdominal fat CT examinations with mean water-equivalent diameter (WED) of 27.8 cm ± 6.0 (range, 17.9 - 42.2 cm). Patient age ranged from 18 to 75 years, and weight ranged from 39 to 163 kg. Results: Mean SSDE was 6.37 mGy ± 1.33 (range, 3.67–8.95 mGy); mean D{sub size,L} was 2.99 mGy ± 0.85 (range, 1.48 - 4.88 mGy); and mean D{sub size,L}/SSDE ratio was 0.46 ± 0.04 (range, 0.40 - 0.55). Conclusion: The conversion factors for size-specific dose estimate in AAPM Report No. 204 were generated using 15 - 30 cm scan lengths. One needs to be cautious in applying SSDE to small length CT scans. For abdominal fat CT, SSDE was 80–150% higher than the dose of 1 cm scan length.« less

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

PubMed

KuKanich, Butch; Warner, Matt; Hahn, Kevin

2017-02-01

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Evaluation and comparison of absorbed dose for electron beams by LiF and diamond dosimeters

NASA Astrophysics Data System (ADS)

Mosia, G. J.; Chamberlain, A. C.

2007-09-01

The absorbed dose response of LiF and diamond thermoluminescent dosimeters (TLDs), calibrated in 60Co γ-rays, has been determined using the MCNP4B Monte Carlo code system in mono-energetic megavoltage electron beams from 5 to 20 MeV. Evaluation of the dose responses was done against the dose responses of published works by other investigators. Dose responses of both dosimeters were compared to establish if any relation exists between them. The dosimeters were irradiated in a water phantom with the centre of their top surfaces (0.32×0.32 cm 2), placed at dmax perpendicular to the radiation beam on the central axis. For LiF TLD, dose responses ranged from 0.945±0.017 to 0.997±0.011. For the diamond TLD, the dose response ranged from 0.940±0.017 to 1.018±0.011. To correct for dose responses by both dosimeters, energy correction factors were generated from dose response results of both TLDs. For LiF TLD, these correction factors ranged from 1.003 up to 1.058 and for diamond TLD the factors ranged from 0.982 up to 1.064. The results show that diamond TLDs can be used in the place of the well-established LiF TLDs and that Monte Carlo code systems can be used in dose determinations for radiotherapy treatment planning.

Site-specific range uncertainties caused by dose calculation algorithms for proton therapy

NASA Astrophysics Data System (ADS)

Schuemann, J.; Dowdell, S.; Grassberger, C.; Min, C. H.; Paganetti, H.

2014-08-01

The purpose of this study was to assess the possibility of introducing site-specific range margins to replace current generic margins in proton therapy. Further, the goal was to study the potential of reducing margins with current analytical dose calculations methods. For this purpose we investigate the impact of complex patient geometries on the capability of analytical dose calculation algorithms to accurately predict the range of proton fields. Dose distributions predicted by an analytical pencil-beam algorithm were compared with those obtained using Monte Carlo (MC) simulations (TOPAS). A total of 508 passively scattered treatment fields were analyzed for seven disease sites (liver, prostate, breast, medulloblastoma-spine, medulloblastoma-whole brain, lung and head and neck). Voxel-by-voxel comparisons were performed on two-dimensional distal dose surfaces calculated by pencil-beam and MC algorithms to obtain the average range differences and root mean square deviation for each field for the distal position of the 90% dose level (R90) and the 50% dose level (R50). The average dose degradation of the distal falloff region, defined as the distance between the distal position of the 80% and 20% dose levels (R80-R20), was also analyzed. All ranges were calculated in water-equivalent distances. Considering total range uncertainties and uncertainties from dose calculation alone, we were able to deduce site-specific estimations. For liver, prostate and whole brain fields our results demonstrate that a reduction of currently used uncertainty margins is feasible even without introducing MC dose calculations. We recommend range margins of 2.8% + 1.2 mm for liver and prostate treatments and 3.1% + 1.2 mm for whole brain treatments, respectively. On the other hand, current margins seem to be insufficient for some breast, lung and head and neck patients, at least if used generically. If no case specific adjustments are applied, a generic margin of 6.3% + 1.2 mm would be needed for breast, lung and head and neck treatments. We conclude that the currently used generic range uncertainty margins in proton therapy should be redefined site specific and that complex geometries may require a field specific adjustment. Routine verifications of treatment plans using MC simulations are recommended for patients with heterogeneous geometries.

Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

PubMed

Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

2010-08-01

The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

Dose density in adjuvant chemotherapy for breast cancer.

PubMed

Citron, Marc L

2004-01-01

Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.

Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bentefour, El H., E-mail: hassan.bentefour@iba-group.com; Prieels, Damien; Tang, Shikui

Purpose: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. Methods: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification inmore » the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. Results: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. Conclusions: Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.« less

Determination of gonad doses during robotic stereotactic radiosurgery for various tumor sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zorlu, Faruk; Dugel, Gozde; Ozyigit, Gokhan

Purpose: The authors evaluated the absorbed dose received by the gonads during robotic stereotactic radiosurgery (SRS) for the treatment of different tumor localizations. Methods: The authors measured the gonad doses during the treatment of head and neck, thoracic, abdominal, or pelvic tumors in both RANDO phantom and actual patients. The computerized tomography images were transferred to the treatment planning system. The contours of tumor and critical organs were delineated on each slice, and treatment plans were generated. Measurements for gonad doses were taken from the geometric projection of the ovary onto the skin for female patients, and from the scrotalmore » skin for male patients by attaching films and Thermoluminescent dosimeters (TLDs). SRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). Results: The median gonadal doses with TLD and film dosimeter in actual patients were 0.19 Gy (range, 0.035-2.71 Gy) and 0.34 Gy (range, 0.066-3.18 Gy), respectively. In the RANDO phantom, the median ovarian doses with TLD and film dosimeter were 0.08 Gy (range, 0.03-0.159 Gy) and 0.05 Gy (range, 0.015-0.13 Gy), respectively. In the RANDO phantom, the median testicular doses with TLD and film dosimeter were 0.134 Gy (range 0.056-1.97 Gy) and 0.306 Gy (range, 0.065-2.25 Gy). Conclusions: Gonad doses are below sterility threshold in robotic SRS for different tumor localizations. However, particular attention should be given to gonads during robotic SRS for pelvic tumors.« less

Preoperative single fraction partial breast radiotherapy for early-stage breast cancer.

PubMed

Palta, Manisha; Yoo, Sua; Adamson, Justus D; Prosnitz, Leonard R; Horton, Janet K

2012-01-01

Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. The median breast volume was 1,713 cm(3) (range: 1,014-2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

PubMed

Troeller, A; Soehn, M; Yan, D

2012-06-01

Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way it is commonly done for the gEUD. © 2012 American Association of Physicists in Medicine.

A dose-volume analysis of magnetic resonance imaging-aided high-dose-rate image-based interstitial brachytherapy for uterine cervical cancer.

PubMed

Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

2010-07-01

To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results. (c) 2010 Elsevier Inc. All rights reserved.

Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.

PubMed

Elmore, E; Lao, X-Y; Kapadia, R; Redpath, J L

2009-06-01

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

PubMed

Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

2013-01-15

We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

PubMed Central

2013-01-01

Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

Estimating thyroid dose in pediatric CT exams from surface dose measurement

NASA Astrophysics Data System (ADS)

Al-Senan, Rani; Mueller, Deborah L.; Hatab, Mustapha R.

2012-07-01

The purpose of this study was to investigate the possibility of estimating pediatric thyroid doses from CT using surface neck doses. Optically stimulated luminescence dosimeters were used to measure the neck surface dose of 25 children ranging in ages between one and three years old. The neck circumference for each child was measured. The relationship between obtained surface doses and thyroid dose was studied using acrylic phantoms of various sizes and with holes of different depths. The ratios of hole-to-surface doses were used to convert patients' surface dose to thyroid dose. ImPACT software was utilized to calculate thyroid dose after applying the appropriate age correction factors. A paired t-test was performed to compare thyroid doses from our approach and ImPACT. The ratio of thyroid to surface dose was found to be 1.1. Thyroid doses ranged from 20 to 80 mGy. Comparison showed no statistical significance (p = 0.18). In addition, the average of surface dose variation along the z-axis in helical scans was studied and found to range between 5% (in 10 cm diameter phantom/24 mm collimation/pitch 1.0) and 8% (in 16 cm diameter phantom/12 mm collimation/pitch 0.7). We conclude that surface dose is an acceptable predictor for pediatric thyroid dose from CT. The uncertainty due to surface dose variability may be reduced if narrower collimation is used with a pitch factor close to 1.0. Also, the results did not show any effect of thyroid depth on the measured dose.

Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification

PubMed Central

Wareham, Alice; Lewandowski, Kuiama S.; Williams, Ann; Dennis, Michael J.; Sharpe, Sally; Vipond, Richard; Silman, Nigel; Ball, Graham

2016-01-01

A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an ‘early’ FOS-associated response, to a ‘late’ predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using comparisons between data outputs of each analytical pipeline and comparisons with previously published Human TB datasets, we have delineated a subset of gene entities which may be of use for biomarker diagnostic test development. PMID:27228113

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

NASA Astrophysics Data System (ADS)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-02-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models.

PubMed

Tian, Xiaoyu; Li, Xiang; Segars, W Paul; Frush, Donald P; Paulson, Erik K; Samei, Ehsan

2013-12-21

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDI(vol)-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDI(vol)-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

Feasibility of RACT for 3D dose measurement and range verification in a water phantom.

PubMed

Alsanea, Fahed; Moskvin, Vadim; Stantz, Keith M

2015-02-01

The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose. Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated. The resulting dosimetric images were reconstructed implementing a 3D filtered backprojection algorithm and the pressure signals acquired from a 71-transducer array with a cylindrical geometry (30 × 40 cm) rotated over 2π about its central axis. Dependencies on the detector bandwidth and proton beam pulse width were performed, after which, different noise levels were added to the detector signals (using 1 μs pulse width and a 0.5 MHz cutoff frequency/hydrophone) to investigate the statistical and systematic errors in the proton range (at 20 cm) and Bragg peak dose (of 1 cGy). The reconstructed radioacoustic computed tomographic image intensity was shown to be linearly correlated to the dose within the Bragg peak. And, based on noise dependent studies, a detector sensitivity of 38 mPa was necessary to determine the proton range to within 1.0 mm (full-width at half-maximum) (systematic error < 150 μm) for a 1 cGy Bragg peak dose, where the integral dose within the Bragg peak was measured to within 2%. For existing hydrophone detector sensitivities, a Bragg peak dose of 1.6 cGy is possible. This study demonstrates that computed tomographic scanner based on ionizing radiation-induced acoustics can be used to verify dose distribution and proton range with centi-Gray sensitivity. Realizing this technology into the clinic has the potential to significantly impact beam commissioning, treatment verification during particle beam therapy and image guided techniques.

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models

NASA Astrophysics Data System (ADS)

Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Frush, Donald P.; Paulson, Erik K.; Samei, Ehsan

2013-12-01

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDIvol-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDIvol-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

DSC studies on gamma irradiated poly(vinylidene fluoride) applied to high gamma dose dosimetry

NASA Astrophysics Data System (ADS)

Batista, Adriana S. M.; Faria, Luiz O.

2017-11-01

Poly(vinylidene fluoride) homopolymer (PVDF) was investigated for use on high gamma dose dosimetry. Samples were irradiated with gamma doses ranging from 100 kGy to 3000 kGy. Differential scanning calorimetry (DSC) was used to construct an unambiguous relationship between the melting transition latent heat (LM) and the absorbed dose (D). DSC thermograms were taken immediately, 1, 2 and 8 months after the irradiation process revealing that the LMx D relationship presented no change for doses ranging from 100 to 2750 kGy. FTIR and UV-Vis spectroscopy data revealed the radio-induction of C˭O and C˭C bonds. These radio-induced bonds were responsible by the chain stiffening and chain oxidation, respectively. SEM microscopy demonstrates that the spherulitic large crystalline structures present in pristine PVDF are destroyed with doses as low as 100 kGy. The DRX analysis revealed that the main effect of high gamma doses in the crystalline structure of PVDF is to provoke a change from the pristine PVDF α-phase to the γ-phase. Both the ability to detect gamma doses in a large dose range and the low fading features make PVDF homopolymers good candidates to be investigated as high gamma dose dosimeters.

Entrance radiation doses during paediatric cardiac catheterisations performed for diagnosis or the treatment of congenital heart disease.

PubMed

Papadopoulou, D; Yakoumakis, Em; Sandilos, P; Thanopoulos, V; Makri, Tr; Gialousis, G; Houndas, D; Yakoumakis, N; Georgiou, Ev

2005-01-01

The purpose of this study was to estimate the radiation exposure of children, during cardiac catheterisations for the diagnosis or treatment of congenital heart disease. Radiation doses were estimated for 45 children aged from 1 d to 13 y old. Thermoluminescent dosemeters (TLDs) were used to estimate the posterior entrance dose (DP), the lateral entrance dose (DLAT), the thyroid dose and the gonads dose. A dose-area product (DAP) meter was also attached externally to the tube of the angiographic system and gave a direct value in mGy cm2 for each procedure. Posterior and lateral entrance dose values during cardiac catheterisations ranged from 1 to 197 mGy and from 1.1 to 250.3 mGy, respectively. Radiation exposure to the thyroid and the gonads ranged from 0.3 to 8.4 mGy to 0.1 and 0.7 mGy, respectively. Finally, the DAP meter values ranged between 360 and 33,200 mGy cm2. Radiation doses measured in this study are comparable with those reported to previous studies. Moreover, strong correlation was found between the DAP values and the entrance radiation dose measured with TLDs.

Sizes of particles formed during municipal wastewater treatment.

PubMed

Lech, Smoczynski; Marta, Kosobucka; Michal, Smoczynski; Harsha, Ratnaweera; Krystyna, Pieczulis-Smoczynska

2017-02-01

Volumetric diameters Dv and specific surface area SpS of sludge particles formed during chemical coagulation and electrocoagulation of sewage were determined. The obtained aggregate-flocs differed substantially in both Dv and SpS values. The differences in Dv and SpS values of the analyzed particles were interpreted based on theoretical models for expanding aggregates. The most uniform particles were formed under exposure to: (a) optimal and maximal doses of PIX, (b) optimal doses of PAX, (c) maximal doses of the Al electro-coagulant. The lowest PIX dose produced the least uniform particles. Sludge aggregates-particles produced under exposure to minimal doses of PIX and the Al electro-coagulant were characterized by the lowest SpS values. Sludge particles coagulated by PAX and the particles formed at higher doses of PIX and the Al electro-coagulant had higher SpS values. The particles formed at all doses of the applied coagulants and electro-coagulants were generally classified into two size ranges: the main range and the secondary range. Most particles belonged to the main size range. An increase in the percentage of colloidal hydroxide particles in sewage sludge increased SpS.

Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.

PubMed

Kampouraki, Emmanouela; Avery, Peter J; Wynne, Hilary; Biss, Tina; Hanley, John; Talks, Kate; Kamali, Farhad

2017-09-01

Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients. © 2017 John Wiley & Sons Ltd.

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

PubMed

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration

NASA Astrophysics Data System (ADS)

Bernatowicz, Kinga; Geets, Xavier; Barragan, Ana; Janssens, Guillaume; Souris, Kevin; Sterpin, Edmond

2018-04-01

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.

SU-F-T-170: Patient Surface Dose Measurements Using Optically Stimulated Luminescence Dosimeters in Scanning Proton Beam Therapy for Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, J; Strauss, D; Langner, U

Purpose: To establish patient surface dose dosimetry for scanning proton beam therapy (SPBT) for breast cancer using optically stimulated luminescence dosimeters (OSLD). Methods: OSLDs were calibrated with SPB under the similar conditions as the treatments for breast cancer. A range shifter (RS) of 5 cm water equivalent thickness (WET) was used. The air gap from the surface of the range shifter to the surface of the phantom was 15 cm. A uniform planar dose generated by nominal energy of 118 MeV was delivered. The range of 118 MeV proton beam after the 5cm RS is approximately 5 cm in water,more » which is the common range for breast treatments. The OSLDs were placed on the surface of high density polyethylene slabs, and a bolus of 1.06 cm WET was used for buildup. A variety of dose levels in the range of 0.5 to 8 Gy were delivered. Under the same condition, an ADCL calibrated parallel plate (PP) chamber was used to measure the reference dose. The correlation between the output signals of OSLDs and the reference doses was established. The calibration of OSLD was verified against the PP chamber measurements for two SPBT breast plans calculated for two patients. Results: the least squares fitting for the OSLD calibration curve was a polynomial function to the order of 2 in the range of 0.5 to 8 Gy (RBE). The differences between the dose measured with OSLDs and PP chamber were within 3% for the two breast proton plans. Conclusion: the calibrated OSLDs under the similar conditions as the treatments can be used for patient surface dose measurements.« less

Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement

PubMed Central

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

Objective To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. Methods We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. Results A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. Conclusions All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement. PMID:24728385

Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement.

PubMed

Zhao, Li; Chen, Chunxia; Li, Bei; Dong, Li; Guo, Yingqiang; Xiao, Xijun; Zhang, Eryong; Qin, Li

2014-01-01

To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88-4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.

Force-related neuronal activity in two regions of the primate ventral premotor cortex.

PubMed

Hepp-Reymond, M C; Hüsler, E J; Maier, M A; Ql, H X

1994-05-01

Neuronal activity was recorded in the ventral premotor cortex of one monkey (Macaca fascicularis) trained to exert finely graded forces with thumb and index finger on a force sensor in a visuomotor step-tracking paradigm. Trials with two or three consecutive ramp-and-hold force steps were presented randomly. Most neurons displayed similar discharge patterns in the two- and three-step trials and were assigned to one of the following classes: phasic, phasic-tonic, tonic, decreasing, and mixed. For more than 50% of the neurons with tonic activity, positive or negative correlations between firing rate and force were statistically significant. The indices of force sensitivity were on average higher for the two-step than for the three-step trials, indicating that the correlations yielded linearity over only a limited force range. The force-related cells were located in two regions of the ventral premotor cortex. One group was ying rostrally within the inferior limb of the arcuate sulcus, from which microstimulation elicited movements of fingers and hand. In the other more caudal region, adjacent to the finger region of primary motor cortex, microstimulation was rarely effective, but all neurons had clear peripheral receptive fields on finger and hand. The data indicate that two populations of neurons, located in the ventral premotor cortex, are related to movement execution. Effective microstimulation also suggests that one of the populations has fairly direct access to the spinal motor apparatus.

Survey of prevalence of overweight body condition in laboratory-housed cynomolgus macaques (Macaca fascicularis).

PubMed

Bauer, Sharon A; Leslie, Ken E; Pearl, David L; Fournier, Jocelyn; Turner, Patricia V

2010-07-01

Excessive weight gain has been reported to occur in captive cynomolgus macaques with little to no change in diet. Overweight body condition can result in development of hyperglycemia and type 2 diabetes and should be avoided. The purpose of this survey was to assess the prevalence of overweight cynomolgus macaques in North American research facilities, including breeding colonies and short-term and long-term facilities, and to describe current methods used to assess body condition. The survey consisted of 51 questions covering animal population demographics, body weight and body condition scoring, feeding, and behavior. Voluntary participants included veterinarians and animal care managers. Respondents from 13 facilities completed the survey, and information was collected on 17,500 cynomolgus macaques. The majority of surveyed facilities housed juvenile and young adult macaques. The reported prevalence of overweight (greater than 10% of ideal body weight) animals ranged between 0% and 20% and reportedly was more frequent in animals younger than 10 y. Most facilities had weight reduction strategies in place. Despite these programs, a significant proportion of animals were reported as being overweight. The results of this survey demonstrate that most North American facilities housing cynomolgus macaques recognize the importance of tracking body condition regularly. However, implementing effective weight reduction programs may be difficult in captive housing environments. Because of the potential for adverse health effects, facilities should have a means of regularly tracking body weight as well as an action plan for managing overweight animals.

Admixture in Humans of Two Divergent Plasmodium knowlesi Populations Associated with Different Macaque Host Species

PubMed Central

Divis, Paul C. S.; Singh, Balbir; Anderios, Fread; Hisam, Shamilah; Matusop, Asmad; Kocken, Clemens H.; Assefa, Samuel A.; Duffy, Craig W.; Conway, David J.

2015-01-01

Human malaria parasite species were originally acquired from other primate hosts and subsequently became endemic, then spread throughout large parts of the world. A major zoonosis is now occurring with Plasmodium knowlesi from macaques in Southeast Asia, with a recent acceleration in numbers of reported cases particularly in Malaysia. To investigate the parasite population genetics, we developed sensitive and species-specific microsatellite genotyping protocols and applied these to analysis of samples from 10 sites covering a range of >1,600 km within which most cases have occurred. Genotypic analyses of 599 P. knowlesi infections (552 in humans and 47 in wild macaques) at 10 highly polymorphic loci provide radical new insights on the emergence. Parasites from sympatric long-tailed macaques (Macaca fascicularis) and pig-tailed macaques (M. nemestrina) were very highly differentiated (FST = 0.22, and K-means clustering confirmed two host-associated subpopulations). Approximately two thirds of human P. knowlesi infections were of the long-tailed macaque type (Cluster 1), and one third were of the pig-tailed-macaque type (Cluster 2), with relative proportions varying across the different sites. Among the samples from humans, there was significant indication of genetic isolation by geographical distance overall and within Cluster 1 alone. Across the different sites, the level of multi-locus linkage disequilibrium correlated with the degree of local admixture of the two different clusters. The widespread occurrence of both types of P. knowlesi in humans enhances the potential for parasite adaptation in this zoonotic system. PMID:26020959

Reticulospinal neurons in the pontomedullary reticular formation of the monkey (Macaca fascicularis).

PubMed

Sakai, S T; Davidson, A G; Buford, J A

2009-11-10

Recent neurophysiological studies indicate a role for reticulospinal neurons of the pontomedullary reticular formation (PMRF) in motor preparation and goal-directed reaching in the monkey. Although the macaque monkey is an important model for such investigations, little is known regarding the organization of the PMRF in the monkey. In the present study, we investigated the distribution of reticulospinal neurons in the macaque. Bilateral injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were made into the cervical spinal cord. A wide band of retrogradely labeled cells was found in the gigantocellular reticular nucleus (Gi) and labeled cells continued rostrally into the caudal pontine reticular nucleus (PnC) and into the oral pontine reticular nucleus (PnO). Additional retrograde tracing studies following unilateral cervical spinal cord injections of cholera toxin subunit B revealed that there were more ipsilateral (60%) than contralateral (40%) projecting cells in Gi, while an approximately 50:50 ratio contralateral to ipsilateral split was found in PnC and more contralateral projections arose from PnO. Reticulospinal neurons in PMRF ranged widely in size from over 50 microm to under 25 microm across the major somatic axis. Labeled giant cells (soma diameters greater than 50 microm) comprised a small percentage of the neurons and were found in Gi, PnC and PnO. The present results define the origins of the reticulospinal system in the monkey and provide an important foundation for future investigations of the anatomy and physiology of this system in primates.

Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

PubMed

Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

2007-05-01

Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

Radiation dose and magnification in pelvic X-ray: EOS™ imaging system versus plain radiographs.

PubMed

Chiron, P; Demoulin, L; Wytrykowski, K; Cavaignac, E; Reina, N; Murgier, J

2017-12-01

In plain pelvic X-ray, magnification makes measurement unreliable. The EOS™ (EOS Imaging, Paris France) imaging system is reputed to reproduce patient anatomy exactly, with a lower radiation dose. This, however, has not been assessed according to patient weight, although both magnification and irradiation are known to vary with weight. We therefore conducted a prospective comparative study, to compare: (1) image magnification and (2) radiation dose between the EOS imaging system and plain X-ray. The EOS imaging system reproduces patient anatomy exactly, regardless of weight, unlike plain X-ray. A single-center comparative study of plain pelvic X-ray and 2D EOS radiography was performed in 183 patients: 186 arthroplasties; 104 male, 81 female; mean age 61.3±13.7years (range, 24-87years). Magnification and radiation dose (dose-area product [DAP]) were compared between the two systems in 186 hips in patients with a mean body-mass index (BMI) of 27.1±5.3kg/m 2 (range, 17.6-42.3kg/m 2 ), including 7 with morbid obesity. Mean magnification was zero using the EOS system, regardless of patient weight, compared to 1.15±0.05 (range, 1-1.32) on plain X-ray (P<10 -5 ). In patients with BMI<25, mean magnification on plain X-ray was 1.15±0.05 (range, 1-1.25) and, in patients with morbid obesity, 1.22±0.06 (range, 1.18-1.32). The mean radiation dose was 8.19±2.63dGy/cm 2 (range, 1.77-14.24) with the EOS system, versus 19.38±12.37dGy/cm 2 (range, 4.77-81.75) with plain X-ray (P<10 -4 ). For BMI >40, mean radiation dose was 9.36±2.57dGy/cm 2 (range, 7.4-14.2) with the EOS system, versus 44.76±22.21 (range, 25.2-81.7) with plain X-ray. Radiation dose increased by 0.20dGy with each extra BMI point for the EOS system, versus 0.74dGy for plain X-ray. Magnification did not vary with patient weight using the EOS system, unlike plain X-ray, and radiation dose was 2.5-fold lower. 3, prospective case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, Bria M.; Brady, Samuel L., E-mail: samuel.brady@stjude.org; Kaufman, Robert A.

Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (CF{sub SSDE}{sup organ}) were then multiplied by patient-specific SSDE to estimate patient organ dose. Themore » CF{sub SSDE}{sup organ} were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. IndividualCF{sub SSDE}{sup organ} were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and CF{sub SSDE}{sup organ}, was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusions: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ±10%. In addition, this study provides a complete list of organ dose correlation factors (CF{sub SSDE}{sup organ}) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE.« less

Thermoluminescence glow-curve characteristics of LiF phosphors at high doses of gamma radiation

NASA Astrophysics Data System (ADS)

Benny, P. G.; Khader, S. A.; Sarma, K. S. S.

2013-05-01

High doses of ionising radiation are becoming increasingly common for radiation-processing applications of various medical, agricultural and polymer products using gamma and electron beams. The objective of this work was to study thermoluminescence (TL) glow-curve characteristics of commonly used commercial LiF TL phosphors at high doses of radiation with a view to use them in dosimetry of radiation-processing applications. The TL properties of TLD 100 and 700 phosphors, procured from the Thermo-Scientific (previously Harshaw) company, have been studied in the dose range of 1-60 kGy. The shift in glow peaks was observed in this dose range. Integral TL responses of TLD 100 and TLD 700 were found to decrease as a linear function of dose in the range of 5-50 kGy. The paper describes initial results related to the glow-curve characteristics of these phosphors.

Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film.

PubMed

Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

2016-01-01

Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were -32.336 and -33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range.

Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film

PubMed Central

Gotanda, Tatsuhiro; Katsuda, Toshizo; Gotanda, Rumi; Kuwano, Tadao; Akagawa, Takuya; Tanki, Nobuyoshi; Tabuchi, Akihiko; Shimono, Tetsunori; Kawaji, Yasuyuki

2016-01-01

Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were −32.336 and −33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range. PMID:28144120

Molecular phylogeny of the hominoid primates as indicated by two-dimensional protein electrophoresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldman, D.; Giri, P.R.; O'Brien, J.O.

1987-05-01

A molecular phylogeny for the hominoid primates was constructed by using genetic distances from a survey of 383 radiolabeled fibroblast polypeptides resolved by two-dimensional electrophoresis (2DE). An internally consistent matrix of Nei genetic distances was generated on the basis of variants in electrophoretic position. The derived phylogenetic tree indicated a branching sequence, from oldest to most recent, of cercopithecoids (Macaca fascicularis), gibbon-siamang, orangutan, gorilla, and human-chimpanzee. A cladistic analysis of 240 electrophoretic characters that varied between ape species produced an identical tree. Genetic distance measures obtained by 2DE are largely consistent with those generated by other molecular procedures. In addition,more » the 2DE data set appears to resolve the human-chimpanzee-gorilla trichotomy in favor of a more recent association of chimpanzees and humans.« less

Characterization of a prototype strain of hepatitis E virus.

PubMed Central

Tsarev, S A; Emerson, S U; Reyes, G R; Tsareva, T S; Legters, L J; Malik, I A; Iqbal, M; Purcell, R H

1992-01-01

A strain of hepatitis E virus (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, was characterized extensively. Six cynomolgus monkeys (Macaca fascicularis) were infected with a strain of hepatitis E virus from Pakistan. Reverse transcription-polymerase chain reaction was used to determine the pattern of virus shedding in feces, bile, and serum relative to hepatitis and induction of specific antibodies. Virtually the entire genome of SAR-55 (7195 nucleotides) was sequenced. Comparison of the sequence of SAR-55 with that of a Burmese strain revealed a high level of homology except for one region encoding 100 amino acids of a putative nonstructural polyprotein. Identification of this region as hypervariable was obtained by partial sequencing of a third isolate of hepatitis E virus from Kirgizia. Images PMID:1731327

Predation on pupa of Chrysomya rufifacies (Marquart) (Diptera: Calliphoridae) by parasitoid, Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae) and Ophyra spinigera larva (Diptera: Muscidae).

PubMed

Chin, Heo Chong; Ahmad, Nazni Wasi; Lim, Lee Han; Jeffery, John; Omar, Baharudin; Dhang, Chen Chee; Weng, Lau Koon; Sofian-Azirun, Mohd

2009-12-01

A forensic entomological study was conducted using monkey carcasses (Macaca fascicularis Raffles) that were placed in either an outdoor or indoor environment at a coastal area in Tanjung Sepat, Selangor, Malaysia during May until August 2008. We collected pupae of Chrysomya rufifacies (Marquart) from the carcasses and kept them individually. The emergence of 13 parasitic microhymenopteran, from one of the pupae occurring within a week were identified as Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae). Another observation was made whereby a pupa of C. rufifacies was predated by a muscid larva, Ophyra spinigera (Stein). The larva squeezed into the pupa and consumed the contents. This paper report C. rufifacies as a new host record for E. philippinensis in Malaysia and highlighted the predatory behavior of O. spinigera larva in natural environment.

Quantitative comparison of the results obtained by the multiple-dose guinea pig maximization test and the non-radioactive murine local lymph-node assay for various biocides.

PubMed

Yamano, Tetsuo; Shimizu, Mitsuru; Noda, Tsutomu

2005-07-01

We compared the results of the multiple-dose guinea pig maximization test (GPMT) and the non-radioactive murine local lymph-node assay (LLNA) for various biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results in the LLNA. In the GPMT, the minimum first induction doses ranged over four orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated using an optimally sensitized group of animals in the multiple-dose studies, ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses ranged over more than three orders (0.01-30%). With respect to 13 biocides that were positive in both the GPMT and the LLNA, results were quantitatively compared. When compared after conversion to corresponding area doses (microg/cm), the minimum doses required to elicit skin reaction in guinea pigs were always lower than that for induction in mice with all biocides. Correlation between minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while that between minimum induction doses in the LLNA and elicitation-threshold doses in the GPMT was relatively good (r=0.73). The results suggest the possibility to estimate human elicitation-threshold doses, which are definitely lacking in the process of risk assessment for skin-sensitizers, from the data of the LLNA.

Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-11-08

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

The nonuniformity of antibody distribution in the kidney and its influence on dosimetry.

PubMed

Flynn, Aiden A; Pedley, R Barbara; Green, Alan J; Dearling, Jason L; El-Emir, Ethaar; Boxer, Geoffrey M; Boden, Robert; Begent, Richard H J

2003-02-01

The therapeutic efficacy of radiolabeled antibody fragments can be limited by nephrotoxicity, particularly when the kidney is the major route of extraction from the circulation. Conventional dose estimates in kidney assume uniform dose deposition, but we have shown increased antibody localization in the cortex after glomerular filtration. The purpose of this study was to measure the radioactivity in cortex relative to medulla for a range of antibodies and to assess the validity of the assumption of uniformity of dose deposition in the whole kidney and in the cortex for these antibodies with a range of radionuclides. Storage phosphor plate technology (radioluminography) was used to acquire images of the distributions of a range of antibodies of various sizes, labeled with 125I, in kidney sections. This allowed the calculation of the antibody concentration in the cortex relative to the medulla. Beta-particle point dose kernels were then used to generate the dose-rate distributions from 14C, 131I, 186Re, 32P and 90Y. The correlation between the actual dose-rate distribution and the corresponding distribution calculated assuming uniform antibody distribution throughout the kidney was used to test the validity of estimating dose by assuming uniformity in the kidney and in the cortex. There was a strong inverse relationship between the ratio of the radioactivity in the cortex relative to that in the medulla and the antibody size. The nonuniformity of dose deposition was greatest with the smallest antibody fragments but became more uniform as the range of the emissions from the radionuclide increased. Furthermore, there was a strong correlation between the actual dose-rate distribution and the distribution when assuming a uniform source in the kidney for intact antibodies along with medium- to long-range radionuclides, but there was no correlation for small antibody fragments with any radioisotope or for short-range radionuclides with any antibody. However, when the cortex was separated from the whole kidney, the correlation between the actual dose-rate distribution and the assumed dose-rate distribution, if the source was uniform, increased significantly. During radioimmunotherapy, the extent of nonuniformity of dose deposition in the kidney depends on the properties of the antibody and radionuclide. For dosimetry estimates, the cortex should be taken as a separate source region when the radiopharmaceutical is small enough to be filtered by the glomerulus.

Age- and gender-specific estimates of cumulative CT dose over 5 years using real radiation dose tracking data in children.

PubMed

Lee, Eunsol; Goo, Hyun Woo; Lee, Jae-Yeong

2015-08-01

It is necessary to develop a mechanism to estimate and analyze cumulative radiation risks from multiple CT exams in various clinical scenarios in children. To identify major contributors to high cumulative CT dose estimates using actual dose-length product values collected for 5 years in children. Between August 2006 and July 2011 we reviewed 26,937 CT exams in 13,803 children. Among them, we included 931 children (median age 3.5 years, age range 0 days-15 years; M:F = 533:398) who had 5,339 CT exams. Each child underwent at least three CT scans and had accessible radiation dose reports. Dose-length product values were automatically extracted from DICOM files and we used recently updated conversion factors for age, gender, anatomical region and tube voltage to estimate CT radiation dose. We tracked the calculated CT dose estimates to obtain a 5-year cumulative value for each child. The study population was divided into three groups according to the cumulative CT dose estimates: high, ≥30 mSv; moderate, 10-30 mSv; and low, <10 mSv. We reviewed clinical data and CT protocols to identify major contributors to high and moderate cumulative CT dose estimates. Median cumulative CT dose estimate was 5.4 mSv (range 0.5-71.1 mSv), and median number of CT scans was 4 (range 3-36). High cumulative CT dose estimates were most common in children with malignant tumors (57.9%, 11/19). High frequency of CT scans was attributed to high cumulative CT dose estimates in children with ventriculoperitoneal shunt (35 in 1 child) and malignant tumors (range 18-49). Moreover, high-dose CT protocols, such as multiphase abdomen CT (median 4.7 mSv) contributed to high cumulative CT dose estimates even in children with a low number of CT scans. Disease group, number of CT scans, and high-dose CT protocols are major contributors to higher cumulative CT dose estimates in children.

Analysis of patient CT dose data using virtualdose

NASA Astrophysics Data System (ADS)

Bennett, Richard

X-ray computer tomography has many benefits to medical and research applications. Recently, over the last decade CT has had a large increase in usage in hospitals and medical diagnosis. In pediatric care, from 2000 to 2006, abdominal CT scans increased by 49 % and chest CT by 425 % in the emergency room (Broder 2007). Enormous amounts of effort have been performed across multiple academic and government groups to determine an accurate measure of organ dose to patients who undergo a CT scan due to the inherent risks with ionizing radiation. Considering these intrinsic risks, CT dose estimating software becomes a necessary tool that health care providers and radiologist must use to determine many metrics to base the risks versus rewards of having an x-ray CT scan. This thesis models the resultant organ dose as body mass increases for patients with all other related scan parameters fixed. In addition to this,this thesis compares a modern dose estimating software, VirtualDose CT to two other programs, CT-Expo and ImPACT CT. The comparison shows how the software's theoretical basis and the phantom they use to represent the human body affect the range of results in organ dose. CT-Expo and ImPACT CT dose estimating software uses a different model for anatomical representation of the organs in the human body and the results show how that approach dramatically changes the outcome. The results categorizes four datasets as compared to the three software types where the appropriate phantom was available. Modeling was done to simulate chest abdominal pelvis scans and whole body scans. Organ dose difference versus body mass index shows as body mass index (BMI) ranges from 23.5 kg/m 2 to 45 kg/m2 the amount of organ dose also trends a percent change from -4.58 to -176.19 %. Comparing organ dose difference with increasing x-ray tube potential from 120 kVp to 140 kVp the percent change in organ dose increases from 55 % to 65 % across all phantoms. In comparing VirtualDose to CT-Expo for organ dose difference versus age, male phantoms show percent difference of -19 % to 25 % for various organs minus bone surface and breast tissues results. Finally, for organ dose difference across all software for average adult phantom the results range from -45 % to 6 % in the comparison of ImPACT CT to VirtualDose and -27 % to 66 % for the comparison of CT-Expo to VirtualDose. In the comparison for increased BMI (done only in VirtualDose), results show that with all other parameters fixed, the organ dose goes down as BMI increases, which is due to the increase in adipose tissue and bulk of the patient model. The range of results when comparing all the three softwares have a wide range, in some cases greater than 150 %, it is evident that using a different anatomical basis for the human phantom and the theoretical basis for the dose estimation will cause fluctuation in the results. Therefore, choosing the software with the most accurate human phantom will provide a closer range to the true dose to the organ.

The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liebl, Jakob, E-mail: jakob.liebl@medaustron.at; Francis H. Burr Proton Therapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Therapeutic Radiology and Oncology, Medical University of Graz, 8036 Graz

2014-09-15

Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patientmore » positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions in the human brain as well as target and OAR dosimetry were studied. Observed range uncertainties were correlated with HIs. The clinical practice of using multiple fields with smeared compensators while avoiding distal OAR sparing is considered to be safe.« less

The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

PubMed Central

Liebl, Jakob; Paganetti, Harald; Zhu, Mingyao; Winey, Brian A.

2014-01-01

Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R2 < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions in the human brain as well as target and OAR dosimetry were studied. Observed range uncertainties were correlated with HIs. The clinical practice of using multiple fields with smeared compensators while avoiding distal OAR sparing is considered to be safe. PMID:25186386

Effective radiation dose of ProMax 3D cone-beam computerized tomography scanner with different dental protocols.

PubMed

Qu, Xing-min; Li, Gang; Ludlow, John B; Zhang, Zu-yan; Ma, Xu-chen

2010-12-01

The aim of this study was to compare effective doses resulting from different scan protocols for cone-beam computerized tomography (CBCT) using International Commission on Radiological Protection (ICRP) 1990 and 2007 calculations of dose. Average tissue-absorbed dose, equivalent dose, and effective dose for a ProMax 3D CBCT with different dental protocols were calculated using thermoluminescent dosimeter chips in a human equivalent phantom. Effective doses were derived using ICRP 1990 and the superseding 2007 recommendations. Effective doses (ICRP 2007) for default patient sizes from small to large ranged from 102 to 298 μSv. The coefficient of determination (R(2)) between tube current and effective dose (ICRP 2007) was 0.90. When scanning with lower resolution settings, the effective doses were reduced significantly (P < .05). ProMax 3D can provide a wide range of radiation dose levels. Reduction in radiation dose can be achieved when using lower settings of exposure parameters. Copyright © 2010 Mosby, Inc. All rights reserved.

In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance.

PubMed

Dipasquale, Giovanna; Nouet, Philippe; Rouzaud, Michel; Dubouloz, Angèle; Miralbell, Raymond; Zilli, Thomas

2014-06-01

To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25-2.02 Gy) and 1.82 Gy (range, 0.19-2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, -0.11/+0.19 Gy, p=0.102) (median difference of 1.1%, range -6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., -8.9%). Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Estimated ultraviolet radiation doses in wetlands in six national parks

USGS Publications Warehouse

Diamond, S.A.; Trenham, P.C.; Adams, Michael J.; Hossack, B.R.; Knapp, R.A.; Stark, L.; Bradford, D.; Corn, P.S.; Czarnowski, K.; Brooks, P.D.; Fagre, D.B.; Breen, B.; Dentenbeck, N.E.; Tonnessen, K.

2005-01-01

Ultraviolet-B radiation (UV-B, 280–320-nm wavelengths) doses were estimated for 1024 wetlands in six national parks: Acadia (Acadia), Glacier (Glacier), Great Smoky Mountains (Smoky), Olympic (Olympic), Rocky Mountain (Rocky), and Sequoia/Kings Canyon (Sequoia). Estimates were made using ground-based UV-B data (Brewer spectrophotometers), solar radiation models, GIS tools, field characterization of vegetative features, and quantification of DOC concentration and spectral absorbance. UV-B dose estimates were made for the summer solstice, at a depth of 1 cm in each wetland. The mean dose across all wetlands and parks was 19.3 W-h m−2 (range of 3.4–32.1 W-h m−2). The mean dose was lowest in Acadia (13.7 W-h m−2) and highest in Rocky (24.4 W-h m−2). Doses were significantly different among all parks. These wetland doses correspond to UV-B flux of 125.0 μW cm−2 (range 21.4–194.7 μW cm−2) based on a day length, averaged among all parks, of 15.5 h. Dissolved organic carbon (DOC), a key determinant of water-column UV-B flux, ranged from 0.6 (analytical detection limit) to 36.7 mg C L−1 over all wetlands and parks, and reduced potential maximal UV-B doses at 1-cm depth by 1%–87 %. DOC concentration, as well as its effect on dose, was lowest in Sequoia and highest in Acadia (DOC was equivalent in Acadia, Glacier, and Rocky). Landscape reduction of potential maximal UV-B doses ranged from zero to 77% and was lowest in Sequoia. These regional differences in UV-B wetland dose illustrate the importance of considering all aspects of exposure in evaluating the potential impact of UV-B on aquatic organisms.

Aripiprazole Lauroxil

PubMed Central

Hard, Marjie L.; Mills, Richard J.; Sadler, Brian M.; Turncliff, Ryan Z.; Citrome, Leslie

2017-01-01

Abstract Background Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Methods Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. Findings The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441–882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. Conclusions This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice. PMID:28350572

SU-C-12A-05: Radiation Dose in High-Pitch Pediatric Cardiac CTA: Correlation Between Lung Dose and CTDIvol, DLP, and Size Specific Dose Estimates (SSDE)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J; Kino, A; Newman, B

2014-06-01

Purpose: To investigate the radiation dose for pediatric high pitch cardiac CTA Methods: A total of 14 cases were included in this study, with mean age of 6.2 years (ranges from 2 months to 15 years). Cardiac CTA was performed using a dual-source CT system (Definition Flash, Siemens). Tube voltage (70, 80 and 100kV) was chosen based on patient weight. All patients were scanned using a high-pitch spiral mode (pitch ranges from 2.5 to 3) with tube current modulation technique (CareDose4D, Siemens). For each case, the three dimensional dose distributions were calculated using a Monte Carlo software package (IMPACT-MC, CTmore » Image GmbH). Scanning parameters of each exam, including tube voltage, tube current, beamshaping filters, beam collimation, were defined in the Monte Carlo calculation. Tube current profile along projection angles was obtained from projection data of each tube, which included data within the over-scanning range along z direction. The volume of lungs was segmented out with CT images (3DSlicer). Lung doses of all patients were calculated and compared with CTDIvol, DLP, and SSDE. Results: The average (range) of CTDIvol, DLP and SSDE of all patients was 1.19 mGy (0.58 to 3.12mGy), 31.54 mGy*cm (12.56 to 99 mGy*cm), 2.26 mGy (1.19 to 6.24 mGy), respectively. Radiation dose to the lungs ranged from 0.83 to 4.18 mGy. Lung doses correlated with CTDIvol, DLP and SSDE with correlation coefficients(k) at 0.98, 0.93, and 0.99. However, for the cases with CTDIvol less than 1mGy, only SSDE preserved a strong correlation with lung doses (k=0.83), while much weaker correlations were found for CTDIvol (k=0.29) and DLP (k=-0.47). Conclusion: Lung doses to pediatric patients during Cardiac CTA were estimated. SSDE showed the most robust correlation with lung doses in contrast to CTDIvol and DLP.« less

Analytical probabilistic proton dose calculation and range uncertainties

NASA Astrophysics Data System (ADS)

Bangert, M.; Hennig, P.; Oelfke, U.

2014-03-01

We introduce the concept of analytical probabilistic modeling (APM) to calculate the mean and the standard deviation of intensity-modulated proton dose distributions under the influence of range uncertainties in closed form. For APM, range uncertainties are modeled with a multivariate Normal distribution p(z) over the radiological depths z. A pencil beam algorithm that parameterizes the proton depth dose d(z) with a weighted superposition of ten Gaussians is used. Hence, the integrals ∫ dz p(z) d(z) and ∫ dz p(z) d(z)2 required for the calculation of the expected value and standard deviation of the dose remain analytically tractable and can be efficiently evaluated. The means μk, widths δk, and weights ωk of the Gaussian components parameterizing the depth dose curves are found with least squares fits for all available proton ranges. We observe less than 0.3% average deviation of the Gaussian parameterizations from the original proton depth dose curves. Consequently, APM yields high accuracy estimates for the expected value and standard deviation of intensity-modulated proton dose distributions for two dimensional test cases. APM can accommodate arbitrary correlation models and account for the different nature of random and systematic errors in fractionated radiation therapy. Beneficial applications of APM in robust planning are feasible.

SU-E-J-146: A Research of PET-CT SUV Range for the Online Dose Verification in Carbon Ion Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, L; Hu, W; Moyers, M

2015-06-15

Purpose: Positron-emitting isotope distributions can be used for the image fusion of the carbon ion planning CT and online target verification PETCT, after radiation in the same decay period,the relationship between the same target volume and the SUV value of different every single fraction dose can be found,then the range of SUV for the radiation target could be decided.So this online range also can provide reference for the correlation and consistency in planning target dose verification and evaluation for the clinical trial. Methods: The Rando head phantom can be used as real body,the 10cc cube volume target contouring is done,beammore » ISO Center depth is 7.6cm and the 90 degree fixed carbon ion beams should be delivered in single fraction effective dose of 2.5GyE,5GyE and 8GyE.After irradiation,390 seconds later the 30 minutes PET-CT scanning is performed,parameters are set to 50Kg virtual weight,0.05mCi activity.MIM Maestro is used for the image processing and fusion,five 16mm diameter SUV spheres have been chosen in the different direction in the target.The average SUV in target for different fraction dose can be found by software. Results: For 10cc volume target,390 seconds decay period,the Single fraction effective dose equal to 2.5Gy,Ethe SUV mean value is 3.42,the relative range is 1.72 to 6.83;Equal to 5GyE,SUV mean value is 9.946,the relative range is 7.016 to 12.54;Equal or above to 8GyE,SUV mean value is 20.496,the relative range is 11.16 to 34.73. Conclusion: Making an evaluation for accuracy of the dose distribution using the SUV range which is from the planning CT with after treatment online PET-CT fusion for the normal single fraction carbon ion treatment is available.Even to the plan which single fraction dose is above 2GyE,in the condition of other parameters all the same,the SUV range is linearly dependent with single fraction dose,so this method also can be used in the hyper-fraction treatment plan.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mead, H; St. Jude Children’s Research Hospital, Memphis, TN; Brady, S

Purpose: To discover if a previously published methodology for estimating patient-specific organ dose in a pediatric population (5–55kg) is translatable to the adult sized patient population (> 55 kg). Methods: An adult male anthropomorphic phantom was scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations in the chest and abdominopelvic regions to determine absolute organ dose. Organ-dose-to-SSDE correlation factors were developed by dividing individual phantom organ doses by SSDE of the phantom; where SSDE was calculated at the center of the scan volume of the chest and abdomen/pelvis separately. Organ dose correlation factors developedmore » in phantom were multiplied by 28 chest and 22 abdominopelvic patient SSDE values to estimate organ dose. The median patient weight from the CT examinations was 68.9 kg (range 57–87 kg) and median age was 17 years (range 13–28 years). Calculated organ dose estimates were compared to published Monte Carlo simulated patient and phantom results. Results: Organ-dose-to-SSDE correlation was determined for a total of 23 organs in the chest and abdominopelvic regions. For organs fully covered by the scan volume, correlation in the chest (median 1.3; range 1.1–1.5) and abdominopelvic (median 0.9; range 0.7–1.0) was 1.0 ± 10%. For organs that extended beyond the scan volume (i.e. skin bone marrow and bone surface) correlation was determined to be a median of 0.3 (range 0.1–0.4). Calculated patient organ dose using patient SSDE agreed to better than 6% (chest) and 15% (abdominopelvic) to published values. Conclusion: This study demonstrated that our previous published methodology for calculating organ dose using patient-specific SSDE for the chest and abdominopelvic regions is translatable to adult sized patients for organs fully covered by the scan volume.« less

Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

PubMed

Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

2017-02-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

Dosimetric properties of a proton beamline dedicated to the treatment of ocular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

2014-01-15

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

SU-E-J-11: Measurement of Eye Lens Dose for Varian On-Board Imaging with Different CBCT Acquisition Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deshpande, S; Dhote, D; Kumar, R

Purpose: To measure actual patient eye lens dose for different cone beam computed tomography (CBCT) acquisition protocol of Varian’s On Board Imagining (OBI) system using Optically Stimulated Luminescence (OSL) dosimeter and study the eye lens dose with patient geometry and distance of isocenter to the eye lens Methods: OSL dosimeter was used to measure eye lens dose of patient. OSL dosimeter was placed on patient forehead center during CBCT image acquisition to measure eye lens dose. For three different cone beam acquisition protocol (standard dose head, low dose head and high quality head) of Varian On-Board Imaging, eye lens dosesmore » were measured. Measured doses were correlated with patient geometry and distance between isocenter to eye lens. Results: Measured eye lens dose for standard dose head was in the range of 1.8 mGy to 3.2 mGy, for high quality head protocol dose was in range of 4.5mGy to 9.9 mGy whereas for low dose head was in the range of 0.3mGy to 0.7mGy. Dose to eye lens is depends upon position of isocenter. For posterioraly located tumor eye lens dose is less. Conclusion: From measured doses it can be concluded that by proper selection of imagining protocol and frequency of imaging, it is possible to restrict the eye lens dose below the new limit set by ICRP. However, undoubted advantages of imaging system should be counter balanced by careful consideration of imaging protocol especially for very intense imaging sequences for Adoptive Radiotherapy or IMRT.« less

Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sailer, Anna M., E-mail: karmanna@stanford.edu; Paulis, Leonie, E-mail: leonie.paulis@mumc.nl; Vergoossen, Laura

PurposeKnowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.Materials and MethodsAll interventional radiologists, vascular surgeons, and technicians wore personal dose meters (PDMs, DoseAware, Philips Healthcare). The dose monitoring system simultaneously registered for each procedure dose-related data as the dose area product (DAP) and effective staff dose (E) from PDMs. Use and type of shielding were recorded separately. All procedures were analyzed according to proceduremore » type; these included among others cerebral interventions (n = 112), iliac and/or caval venous recanalization procedures (n = 68), endovascular aortic repair procedures (n = 63), biliary duct interventions (n = 58), and percutaneous gastrostomy procedure (n = 28).ResultsMedian (±IQR) DAP doses ranged from 2.0 (0.8–3.1) (percutaneous gastrostomy) to 84 (53–147) Gy cm{sup 2} (aortic repair procedures). Median (±IQR) first operator doses ranged from 1.6 (1.1–5.0) μSv to 33.4 (12.1–125.0) for these procedures, respectively. The relative exposure, determined as first operator dose normalized to procedural DAP, ranged from 1.9 in biliary interventions to 0.1 μSv/Gy cm{sup 2} in cerebral interventions, indicating large variation in staff dose per unit DAP among the procedure types.ConclusionReal-time dose monitoring was able to identify the types of interventions with either an absolute or relatively high staff dose, and may allow for specific optimization of radiation protection.« less

Correlation of Radiation Dose Estimates by DIC with the METREPOL Hematological Classes of Disease Severity.

PubMed

Port, M; Pieper, B; Dörr, H D; Hübsch, A; Majewski, M; Abend, M

2018-05-01

The degree of severity of hematologic acute radiation syndrome (HARS) may vary across the range of radiation doses, such that dose alone may be a less reliable predictor of clinical course. We sought to elucidate the relationship between absorbed dose and risk of clinically relevant HARS in humans. We used the database SEARCH (System for Evaluation and Archiving of Radiation Accidents based on Case Histories), which contains the histories of radiation accident victims. From 153 cases we extracted data on dose estimates using the dicentric assay to measure individual biological dosimetry. The data were analyzed according to the corresponding hematological response categories of clinical significance (H1-4). These categories are derived from the medical treatment protocols for radiation accident victims (METREPOL) and represent the clinical outcome of HARS based on severity categories ranging from 1-4. In addition, the category H0 represents a post-exposure hematological response that is within the normal range for nonexposed individuals. Age at exposure, gender and ethnicity were considered as potential confounders in unconditional cumulative logistic regression analysis. In most cases, victims were Caucasian (82.4%) and male (92.8%), who originated from either the Chernobyl (69.3%) or Goiânia (10.5%) accident, and nearly 60% were aged 20-40 years at time of exposure. All individuals were whole-body exposed (mean 3.8 Gy, stdev ±3.1), and single exposures were predominantly reported (79%). Seventy percent of victims in category H0 were exposed to ≤1 Gy, with rapidly decreasing proportions of H0 seen at doses up to 5 Gy. There were few HARS H4 cases reported at exposed dose of 1-2 Gy, while 82% of H4 cases received doses of >5 Gy. HARS H1-3 cases varied among dose ranges from 1-5 Gy. In summary, single whole-body radiation doses <1 Gy and >5 Gy corresponded in general with H0 and H3-4, respectively, and this was consistent with medical expectations. This underlines the usefulness of dose estimates for HARS prediction. However, whole-body doses between 1-5 Gy poorly corresponded to HARS H1-3. The dose range of 1-5 Gy was of limited value for medical decision-making regarding, e.g., hospitalization for H2-3, but not H1 and treatment decisions that differ between H1-3. Also, there were some H0 cases at high doses and H2-4 cases at low doses, thereby challenging an individual recommendation based solely on dose.

An end-to-end assessment of range uncertainty in proton therapy using animal tissues.

PubMed

Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

2016-11-21

Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams' superior dose advantage over conventional photon-based radiation therapy.

Methods for Probabilistic Radiological Dose Assessment at a High-Level Radioactive Waste Repository.

NASA Astrophysics Data System (ADS)

Maheras, Steven James

Methods were developed to assess and evaluate the uncertainty in offsite and onsite radiological dose at a high-level radioactive waste repository to show reasonable assurance that compliance with applicable regulatory requirements will be achieved. Uncertainty in offsite dose was assessed by employing a stochastic precode in conjunction with Monte Carlo simulation using an offsite radiological dose assessment code. Uncertainty in onsite dose was assessed by employing a discrete-event simulation model of repository operations in conjunction with an occupational radiological dose assessment model. Complementary cumulative distribution functions of offsite and onsite dose were used to illustrate reasonable assurance. Offsite dose analyses were performed for iodine -129, cesium-137, strontium-90, and plutonium-239. Complementary cumulative distribution functions of offsite dose were constructed; offsite dose was lognormally distributed with a two order of magnitude range. However, plutonium-239 results were not lognormally distributed and exhibited less than one order of magnitude range. Onsite dose analyses were performed for the preliminary inspection, receiving and handling, and the underground areas of the repository. Complementary cumulative distribution functions of onsite dose were constructed and exhibited less than one order of magnitude range. A preliminary sensitivity analysis of the receiving and handling areas was conducted using a regression metamodel. Sensitivity coefficients and partial correlation coefficients were used as measures of sensitivity. Model output was most sensitive to parameters related to cask handling operations. Model output showed little sensitivity to parameters related to cask inspections.

SU-F-J-197: A Novel Intra-Beam Range Detection and Adaptation Strategy for Particle Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, M; Jiang, S; Shao, Y

2016-06-15

Purpose: In-vivo range detection/verification is crucial in particle therapy for effective and safe delivery. The state-of-art techniques are not sufficient for in-vivo on-line range verification due to conflicts among patient dose, signal statistics and imaging time. We propose a novel intra-beam range detection and adaptation strategy for particle therapy. Methods: This strategy uses the planned mid-range spots as probing beams without adding extra radiation to patients. Such choice of probing beams ensures the Bragg peaks to remain inside the tumor even with significant range variation from the plan. It offers sufficient signal statistics for in-beam positron emission tomography (PET) duemore » to high positron activity of therapeutic dose. The probing beam signal can be acquired and reconstructed using in-beam PET that allows for delineation of the Bragg peaks and detection of range shift with ease of detection enabled by single-layered spots. If the detected range shift is within a pre-defined tolerance, the remaining spots will be delivered as the original plan. Otherwise, a fast re-optimization using range-shifted beamlets and accounting for the probing beam dose is applied to consider the tradeoffs posed by the online anatomy. Simulated planning and delivery studies were used to demonstrate the effectiveness of the proposed techniques. Results: Simulations with online range variations due to shifts of various foreign objects into the beam path showed successful delineation of the Bragg peaks as a result of delivering probing beams. Without on-line delivery adaptation, dose distribution was significantly distorted. In contrast, delivery adaptation incorporating detected range shift recovered well the planned dose. Conclusion: The proposed intra-beam range detection and adaptation utilizing the planned mid-range spots as probing beams, which illuminate the beam range with strong and accurate PET signals, is a safe, practical, yet effective approach to address range uncertainty issues in particle therapy.« less

Variation in Prescribing Patterns and Therapeutic Drug Monitoring of Intravenous Busulfan in Pediatric Hematopoietic Cell Transplant Recipients

PubMed Central

McCune, Jeannine S.; Baker, K. Scott; Blough, David K.; Gamis, Alan; Bemer, Meagan J.; Kelton-Rehkopf, Megan C.; Winter, Laura; Barrett, Jeffrey S.

2016-01-01

Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors’ group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children. PMID:23444282

Dose Response Data for Hormonally Active Chemicals ...

EPA Pesticide Factsheets

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

The impact of different algorithms for ideal body weight on screening for hydroxychloroquine retinopathy in women.

PubMed

Browning, David J; Lee, Chong; Rotberg, David

2014-01-01

To determine how algorithms for ideal body weight (IBW) affect hydroxychloroquine dosing in women. This was a retrospective study of 520 patients screened for hydroxychloroquine retinopathy. Charts were reviewed for sex, height, weight, and daily dose. The outcome measures were ranges of IBW across algorithms; rates of potentially toxic dosing; height thresholds below which 400 mg/d dosing is potentially toxic; and rates for which actual body weight (ABW) was less than IBW. Women made up 474 (91%) of the patients. The IBWs for a height varied from 30-34 pounds (13.6-15.5 kg) across algorithms. The threshold heights below which toxic dosing occurred varied from 62-70 inches (157.5-177.8 cm). Different algorithms placed 16%-98% of women in the toxic dosing range. The proportion for whom dosing should have been based on ABW rather than IBW ranged from 5%-31% across algorithms. Although hydroxychloroquine dosing should be based on the lesser of ABW and IBW, there is no consensus about the definition of IBW. The Michaelides algorithm is associated with the most frequent need to adjust dosing; the Metropolitan Life Insurance, large frame, mean value table with the least frequent need. No evidence indicates that one algorithm is superior to others.

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases

NASA Astrophysics Data System (ADS)

Denis-Bacelar, Ana M.; Chittenden, Sarah J.; Murray, Iain; Divoli, Antigoni; McCready, V. Ralph; Dearnaley, David P.; O'Sullivan, Joe M.; Johnson, Bernadette; Flux, Glenn D.

2017-04-01

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r  =  0.98, P  <  0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

Food irradiation dosimetry by opti-chromic technique

NASA Astrophysics Data System (ADS)

Zhan-Jun, Liu; Radak, B. B.; McLaughlin, W. L.

The measurement of gamma-radiation quantities, e.g., absorbed dose in materials such as water, plastics, foodstuffs, is a convenient means of quality assurance in radiation processing. A new dosimetry system, called the "Opti-Chromic" dosimeter, is commercially available in large batches for use as a routine measurement system in the absorbed dose range 10 to 2x10 4 Gy. This dose range covers most food irradiation applications. A statistical evaluation was made of the reproducibility of this dosimeter for measuring doses appropriate for the disinfestation and shelf-life extension of many foods, namely 10 to 2x10 3 Gy. In addition, the small dosimeters were used to map absorbed dose distributions in boxes of foods having four different bulk densities (grapefruit, lemons, peanuts, and wheat bran). It is demonstrated that the dosimeters are rugged and stable enough to be used over a wide temperature and humidity range, and, in fact, can be placed in such environments as the inside of citrus fruits without adverse effects on their ability to give satisfactory dose assessment.

Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

PubMed

Hard, Marjie L; Mills, Richard J; Sadler, Brian M; Turncliff, Ryan Z; Citrome, Leslie

2017-06-01

Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441-882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

PubMed

Karlsson, Kristin; Nyman, Jan; Baumann, Pia; Wersäll, Peter; Drugge, Ninni; Gagliardi, Giovanna; Johansson, Karl-Axel; Persson, Jan-Olov; Rutkowska, Eva; Tullgren, Owe; Lax, Ingmar

2013-11-01

To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D(0.1cm3)) was used for further analysis. The median value of D(0.1cm3) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown. Copyright © 2013 Elsevier Inc. All rights reserved.

Gafchromic EBT‐XD film: Dosimetry characterization in high‐dose, volumetric‐modulated arc therapy

PubMed Central

Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-01-01

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT‐XD films have been designed for optimal performance in the 40–4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose‐response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high‐dose volumetric‐modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0–4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter‐free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose‐rate dependence. For clinical examinations, we compared the dose distribution measured with EBT‐XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT‐XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ∼3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ∼1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ∼1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film‐ measured and treatment planning system (TPS)‐calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. PACS number(s): 87.56 Fc PMID:27929504

SU-E-T-616: Comparison of Plan Dose Accuracy for Anterior Vs. Lateral Fields in Proton Therapy of Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moteabbed, M; Trofimov, A; Testa, M

2014-06-01

Purpose: With the anticipated introduction of in vivo range verification methods, the use of anterior fields for proton therapy of prostate cancer may become an attractive treatment option, and improve upon the dose distributions achievable with conventional lateral-opposed fields. This study aimed to evaluate and compare the planned dose accuracy for lateral versus anterior oblique field arrangements. Methods: Four patients with low/intermediate risk prostate cancer, participating in a clinical trial at our institution, were selected for this study. All patients were treated using lateral-opposed fields (LAT). The clinical target volume (CTV) received a total dose of 79.2 Gy in 44more » fractions. Anterior oblique research plans (ANT) were created using the clinical planning system, and featured beams with ±35-degree gantry angle, 1.2 cm aperture margins, 3-mm range compensator smearing and no range uncertainty margins. Monte Carlo (MC) simulations were performed for both beam arrangements using TOPAS. Dose volume histograms were analyzed and compared for planned and MC dose distributions. Differences between MC and planned DVH parameters were computed as a percentage of the total prescribed dose. Results: For all patients, CTV dose was systematically lower (∼2–2.5%) for MC than the plan. This discrepancy was slightly larger (∼0.5%) for LAT compared to ANT plans for all cases. Although the dose differences for bladder and anterior rectal wall remained within 0.7% for all LAT cases, they were slightly larger for ANT plans, especially for case 3 due to larger patient size and MC-plan range difference. The EUD difference for femoral heads was within 0.6% for both LAT and ANT cases. Conclusion: The dose calculated by the treatment planning system using pencil beam algorithm agrees with MC to within 2.5% and is comparable for lateral and anterior scenarios. The dose agreement in the anterior rectal wall is range- and hence, patient-dependent for ANT treatments.« less

IMRT and RapidArc commissioning of a TrueBeam linear accelerator using TG-119 protocol cases.

PubMed

Wen, Ning; Zhao, Bo; Kim, Jinkoo; Chin-Snyder, Karen; Bellon, Maria; Glide-Hurst, Carri; Barton, Kenneth; Chen, Daiquan; Chetty, Indrin J

2014-09-08

The purpose of this study is to evaluate the overall accuracy of intensity-modulated radiation therapy (IMRT) and RapidArc delivery using both flattening filter (FF) and flattening filter-free (FFF) modalities based on test cases developed by AAPM Task Group 119. Institutional confidence limits (CLs) were established as the baseline for patient specific treatment plan quality assurance (QA). The effects of gantry range, gantry speed, leaf speed, dose rate, as well as the capability to capture intentional errors, were evaluated by measuring a series of Picket Fence (PF) tests using the electronic portal imaging device (EPID) and EBT3 films. Both IMRT and RapidArc plans were created in a Solid Water phantom (30 × 30 × 15 cm3) for the TG-119 test cases representative of normal clinical treatment sites for all five photon energies (6X, 10X, 15X, 6X-FFF, 10X-FFF) and the Exact IGRT couch was included in the dose calculation. One high-dose point in the PTV and one low-dose point in the avoidance structure were measured with an ion chamber in each case for each energy. Similarly, two GAFCHROMIC EBT3 films were placed in the coronal planes to measure planar dose distributions in both high- and low-dose regions. The confidence limit was set to have 95% of the measured data fall within the tolerance. The mean of the absolute dose deviation for variable dose rate and gantry speed during RapidArc delivery was within 0.5% for all energies. The corresponding results for leaf speed tests were all within 0.4%. The combinations of dynamic leaf gap (DLG) and MLC transmission factor were optimized based on the ion chamber measurement results of RapidArc delivery for each energy. The average 95% CLs for the high-dose point in the PTV were 0.030 ± 0.007 (range, 0.022-0.038) for the IMRT plans and 0.029 ± 0.011 (range, 0.016-0.043) for the RapidArc plans. For low-point dose in the avoidance structures, the CLs were 0.029 ± 0.006 (range, 0.024-0.039) for the IMRT plans and 0.027 ± 0.013 (range, 0.017-0.047) for the RapidArc plans. The average 95% CLs using 3%/3 mm gamma criteria in the high-dose region were 5.9 ± 2.7 (range, 1.4-8.6) and 3.9 ± 2.9 (range, 1.5-8.8) for IMRT and RapidArc plans, respectively. The average 95% CLs in the low-dose region were 5.3 ± 2.6 (range, 1.2-7.4) and 3.7 ± 2.8 (range, 1.8-8.3) for IMRT and RapidArc plans, respectively. Based on ion chamber, as well as film measurements, we have established CLs values to ensure the high precision of IMRT and RapidArc delivery for both FF and FFF modalities.

SU-E-T-75: A Simple Technique for Proton Beam Range Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burgdorf, B; Kassaee, A; Garver, E

2015-06-15

Purpose: To develop a measurement-based technique to verify the range of proton beams for quality assurance (QA). Methods: We developed a simple technique to verify the proton beam range with in-house fabricated devices. Two separate devices were fabricated; a clear acrylic rectangular cuboid and a solid polyvinyl chloride (PVC) step wedge. For efficiency in our clinic, we used the rectangular cuboid for double scattering (DS) beams and the step wedge for pencil beam scanning (PBS) beams. These devices were added to our QA phantom to measure dose points along the distal fall-off region (between 80% and 20%) in addition tomore » dose at mid-SOBP (spread out Bragg peak) using a two-dimensional parallel plate chamber array (MatriXX™, IBA Dosimetry, Schwarzenbruck, Germany). This method relies on the fact that the slope of the distal fall-off is linear and does not vary with small changes in energy. Using a multi-layer ionization chamber (Zebra™, IBA Dosimetry), percent depth dose (PDD) curves were measured for our standard daily QA beams. The range (energy) for each beam was then varied (i.e. ±2mm and ±5mm) and additional PDD curves were measured. The distal fall-off of all PDD curves was fit to a linear equation. The distal fall-off measured dose for a particular beam was used in our linear equation to determine the beam range. Results: The linear fit of the fall-off region for the PDD curves, when varying the range by a few millimeters for a specific QA beam, yielded identical slopes. The calculated range based on measured point dose(s) in the fall-off region using the slope resulted in agreement of ±1mm of the expected beam range. Conclusion: We developed a simple technique for accurately verifying the beam range for proton therapy QA programs.« less

Radiosurgery for Para-IAC Meningiomas: The Effect of Radiation Dose to the Cochlea on Hearing Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young-Hoon; Department of Neurosurgery, Seoul National University College of Medicine, Seoul; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr

2012-11-01

Purpose: This study was performed to assess the radiosurgical results of meningiomas extending into the internal acoustic canal (para-IAC meningiomas), with a particular focus on the effect of radiation dose to the cochlea on hearing outcome. Methods and Materials: A total of 50 patients who underwent radiosurgery for para-IAC meningiomas between 1998 and 2009, which were followed for 2 years, were enrolled. The mean age was 55.8 years (range, 15-75). The mean tumor volume was 6.1 cm{sup 3} (range, 1.0-19.0), the mean tumor length in the IAC was 6.9 mm (range, 1.3-13.3), and the mean prescribed marginal dose was 13.1more » Gy (range, 10-15) at an isodose line of 50%. The mean follow-up duration was 46 months (range, 24-122). Results: Eight (16.0%) patients had nonserviceable hearing at the time of surgery. At the last follow-up, the tumor control rate was 94%; unchanged in 17 patients, decreased in 30 patients, and increased in 3 patients. Among 42 patients with serviceable hearing at the time of radiosurgery, it was preserved in 41 (97.6%) patients at the last follow-up. The maximal and mean radiation doses to the cochleae of these 41 patients were 5.8 Gy {+-} 0.3 (range, 3.1-11.5) and 4.3 Gy {+-} 0.2 (range, 2.2-7.5), respectively. The maximal dose to the cochlea of the patient who lost hearing after radiosurgery was 4.7 Gy. Conclusions: The radiation dose to the cochlea may have the minimal toxic effect on the hearing outcome in patients who undergo radiosurgery for para-IAC meningiomas.« less

Extended range radiation dose-rate monitor

DOEpatents

Valentine, Kenneth H.

1988-01-01

An extended range dose-rate monitor is provided which utilizes the pulse pileup phenomenon that occurs in conventional counting systems to alter the dynamic response of the system to extend the dose-rate counting range. The current pulses from a solid-state detector generated by radiation events are amplified and shaped prior to applying the pulses to the input of a comparator. The comparator generates one logic pulse for each input pulse which exceeds the comparator reference threshold. These pulses are integrated and applied to a meter calibrated to indicate the measured dose-rate in response to the integrator output. A portion of the output signal from the integrator is fed back to vary the comparator reference threshold in proportion to the output count rate to extend the sensitive dynamic detection range by delaying the asymptotic approach of the integrator output toward full scale as measured by the meter.

Dosimetry study of diagnostic X-ray using doped iodide normoxic polymer gels

NASA Astrophysics Data System (ADS)

Huang, Y. R.; Chang, Y. J.; Hsieh, L. L.; Liu, M. H.; Liu, J. S.; Chu, C. H.; Hsieh, B. T.

2014-11-01

In radiotherapy, polymer gel dosimeters are used for three-dimensional (3D) dose distribution. However, the doses are within the Gy range. In this study, we attempted to develop a low-dose 3D dosimeter within the mGy range for diagnostic radiology. The effect of the iodinated compound was used as a dose enhancement sensitizer to enhance the dose sensitivity of normoxic polymer gel dosimeters. This study aims to use N-isopropylacrylamide(NIPAM)-based and methacrylic acid (MAGAT)-based gels to evaluate the potential dose enhancement sensitizer, as well as to compare two gels that may be suitable for measuring diagnostic radiation doses. The suitable formulation of NIPAM gel [5% (w/w) gelatin, 5% (w/w) NIPAM, 3% (w/w) N,N‧-methylenebisacrylamide (BIS), 5 mM tetrakis (hydroxymethyl) phosphonium chloride (THPC), and 87% (w/w) deionized distilled water] and MAGAT gel (4% MAA, 9% gelatin, 87% deionized water, and 10 mM THPC) were used and loaded with clinical iodinated contrast medium agent (Iobitridol, Xenetix® 350). Irradiation was conducted using X-ray computed tomography. The irradiation doses ranged from 0 mGy to 80 mGy. Optical computed tomography was the employed gel measurement system. The results indicate that the iodinated contrast agent yields a quantifiable dose enhancement ratio. The dose enhancement ratios of NIPAM and MAGAT gels are 3.35±0.6 and 1.36±0.3, respectively. The developed NIPAM gel in this study could be suitable for measuring diagnostic radiation doses.

Study of the Phototransference in GR-200 Dosimetric Material and its Convenience for Dose Re-estimation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baly, L.; Otazo, M. R.; Molina, D.

2006-09-08

A study of the phototransference of charges from deep to dosimetric traps in GR-200 material is presented and its convenience for dose re-estimation in the dose range between 2 and 100mSv is also analyzed. The recovering coefficient (RC) defined as the ratio between the phototransferred thermoluminescence (PTTL) and the original thermoluminescence (TL) of the dosimetric trap was used to evaluate the ratio of phototransferred charges from deep traps and the original charges in the dosimetric traps. The results show the convenience of this method for dose re-estimation for this material in the selected range of doses.

Flat Ge-doped optical fibres for food irradiation dosimetry

NASA Astrophysics Data System (ADS)

Noor, N. Mohd; Jusoh, M. A.; Razis, A. F. Abdull; Alawiah, A.; Bradley, D. A.

2015-04-01

Exposing food to radiation can improve hygiene quality, germination control, retard sprouting, and enhance physical attributes of the food product. To provide for food safety, radiation dosimetry in irradiated food is required. Herein, fabricated germanium doped (Ge-doped) optical fibres have been used. The fibres have been irradiated using a gamma source irradiator, doses in the range 1 kGy to 10 kGy being delivered. Using Ge-doped optical fibres of variable size, type and dopant concentration, study has been made of linearity, reproducibility, and fading. The thermoluminescence (TL) yield of the fibres were obtained and compared. The fibres exhibit a linear dose response over the investigated range of doses, with mean reproducibility to within 2.69 % to 8.77 %, exceeding the dose range of all commercial dosimeters used in evaluating high doses for the food irradiation industry. TL fading of the Ge-doped flat fibres has been found to be < 13%.

EPR TOOTH DOSIMETRY OF SNTS AREA INHABITANTS.

PubMed

Sholom, Sergey; Desrosiers, Marc; Bouville, André; Luckyanov, Nicholas; Chumak, Vadim; Simon, Steven L

2007-07-01

The determination of external dose to teeth of inhabitants of settlements near the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry technique to assess radiation doses associated with exposure to radioactive fallout from the test site. In this study, tooth doses have been reconstructed for 103 persons with all studied teeth having been formed before the first nuclear test in 1949. Doses above those received from natural background radiation, termed "accident doses", were found to lie in the range from zero to approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk city was approximately 9 Gy. The variability of reconstructed doses within each of the settlements demonstrated heterogeneity of the deposited fallout as well as variations in lifestyle. The village mean external gamma doses for residents of nine[ settlements were in the range from a few tens of mGy to approximately 100 mGy.

Assessment of pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers.

PubMed

Lim, Mi-sun; Seong, Sook Jin; Park, Jeonghyeon; Seo, Jeong Ju; Lee, Joomi; Yu, Kyung-Sang; Lee, Hae Won; Yoon, Young-Ran

2012-04-01

Levofloxacin and cyclosporine show different pharmacokinetic properties, but are known to be dose proportional within the therapeutic range. The authors evaluated the pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two independent, randomized, crossover studies were performed. For levofloxacin, eight volunteers were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or intravenously, followed by a 1-week washout period and administration via the alternate route. After another 1-week washout period, a therapeutic dose (750 mg) was administered to all eight subjects. For cyclosporine, another eight volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with a 1-week washout period. Drug concentrations were determined by LC-MS/MS. For levofloxacin, the mean values for dose-normalized C(max) and AUC(last) with the two doses were as follows: therapeutic dose, 15.2 ± 4.6 ng/ml/mg and 103.6 ± 15.5 ng·h/ml/mg, respectively; low dose, 17.1 ± 6.5 ng/ml/mg and 72.6 ± 8.7 ng·h/ml/mg, respectively. For cyclosporine, the mean values for dose-normalized C(max) and AUC(last) were as follows: therapeutic dose, 4.9 ± 1.5 ng/ml/mg and 15.4 ± 4.9 ng·h/ml/mg, respectively; low dose, 1.6 ± 0.6 ng/ml/mg and 9.3 ± 7.3 ng·h/ml/mg, respectively. In this study levofloxacin, which is completely absorbed and primarily eliminated renally without modification, showed better pharmacokinetic proportionality than cyclosporine, which is poorly absorbed and extensively metabolized.

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women
.

PubMed

Schultze-Mosgau, Marcus-Hillert; Schuett, Barbara; Hafner, Frank-Thorsten; Zollmann, Frank; Kaiser, Andreas; Hoechel, Joachim; Rohde, Beate

2017-01-01

Vilaprisan is a novel, potent, and highly selective progesterone receptor modulator, which might offer a promising option for the treatment of uterine fibroids. In this randomized, placebo-controlled, parallel-group phase 1 study, the pharmacokinetics and safety of vilaprisan were investigated in healthy postmenopausal women. Subjects received a single oral dose of vilaprisan (1, 5, 15, or 30 mg) or placebo and - after a wash-out period - daily doses of the same strength over 28 days. Safety assessments included vital signs, ECGs, clinical laboratory tests, and adverse events. Blood samples for pharmacokinetic (PK) profiles were collected over 14 days after single dose (sd) and multiple dose (md; day 28). Vilaprisan was well tolerated. Mild to moderate adverse events occurred with similar frequency at all dose levels. Following single dose, maximum vilaprisan concentrations were observed 1 - 2 hours post-dose. Terminal half-lives ranged from 31 to 38 hours. Maximum concentrations of vilaprisan (Cmax) and exposure to vilaprisan (AUC) increased roughly dose-proportionally from 3.74 µg/L (1 mg) to 68.6 µg/L (30 mg) and 58.5 µg×h/L to 1,590 µg×h/L, respectively. With daily dosing, accumulation consistent with the long terminal half-life was observed (AUC(0-24)md/AUC(0-24)sd ratios: 1.9 to 3.2). The ratio AUC(0-24)md/AUCsd increased with dose from ~ 1 (1 mg) to 1.5 (30 mg). Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range.
.

SU-E-T-396: Dosimetric Accuracy of Proton Therapy for Patients with Metal Implants in CT Scans Using Metal Deletion Technique (MDT) Artifacts Reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X; Kantor, M; Zhu, X

2014-06-01

Purpose: To evaluate the dosimetric accuracy for proton therapy patients with metal implants in CT using metal deletion technique (MDT) artifacts reduction. Methods: Proton dose accuracies under CT metal artifacts were first evaluated using a water phantom with cylindrical inserts of different materials (titanium and steel). Ranges and dose profiles along different beam angles were calculated using treatment planning system (Eclipse version 8.9) on uncorrected CT, MDT CT, and manually-corrected CT, where true Hounsfield units (water) were assigned to the streak artifacts. In patient studies, the treatment plans were developed on manually-corrected CTs, then recalculated on MDT and uncorrected CTs.more » DVH indices were compared between the dose distributions on all the CTs. Results: For water phantom study with 1/2 inch titanium insert, the proton range differences estimated by MDT CT were with 1% for all beam angles, while the range error can be up to 2.6% for uncorrected CT. For the study with 1 inch stainless steel insert, the maximum range error calculated by MDT CT was 1.09% among all the beam angles compared with maximum range error with 4.7% for uncorrected CT. The dose profiles calculated on MDT CTs for both titanium and steel inserts showed very good agreements with the ones calculated on manually-corrected CTs, while large dose discrepancies calculated using uncorrected CTs were observed in the distal end region of the proton beam. The patient study showed similar dose distribution and DVHs for organs near the metal artifacts recalculated on MDT CT compared with the ones calculated on manually-corrected CT, while the differences between uncorrected and corrected CTs were much pronounced. Conclusion: In proton therapy, large dose error could occur due to metal artifact. The MDT CT can be used for proton dose calculation to achieve similar dose accuracy as the current clinical practice using manual correction.« less

Measured Neutron Spectra and Dose Equivalents From a Mevion Single-Room, Passively Scattered Proton System Used for Craniospinal Irradiation.

PubMed

Howell, Rebecca M; Burgett, Eric A; Isaacs, Daniel; Price Hedrick, Samantha G; Reilly, Michael P; Rankine, Leith J; Grantham, Kevin K; Perkins, Stephanie; Klein, Eric E

2016-05-01

To measure, in the setting of typical passively scattered proton craniospinal irradiation (CSI) treatment, the secondary neutron spectra, and use these spectra to calculate dose equivalents for both internal and external neutrons delivered via a Mevion single-room compact proton system. Secondary neutron spectra were measured using extended-range Bonner spheres for whole brain, upper spine, and lower spine proton fields. The detector used can discriminate neutrons over the entire range of the energy spectrum encountered in proton therapy. To separately assess internally and externally generated neutrons, each of the fields was delivered with and without a phantom. Average neutron energy, total neutron fluence, and ambient dose equivalent [H* (10)] were calculated for each spectrum. Neutron dose equivalents as a function of depth were estimated by applying published neutron depth-dose data to in-air H* (10) values. For CSI fields, neutron spectra were similar, with a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate continuum between the evaporation and thermal peaks. Neutrons in the evaporation peak made the largest contribution to dose equivalent. Internal neutrons had a very low to negligible contribution to dose equivalent compared with external neutrons, largely attributed to the measurement location being far outside the primary proton beam. Average energies ranged from 8.6 to 14.5 MeV, whereas fluences ranged from 6.91 × 10(6) to 1.04 × 10(7) n/cm(2)/Gy, and H* (10) ranged from 2.27 to 3.92 mSv/Gy. For CSI treatments delivered with a Mevion single-gantry proton therapy system, we found measured neutron dose was consistent with dose equivalents reported for CSI with other proton beamlines. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

PubMed

Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

2016-02-01

Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to healthy volunteers. The absolute bioavailability of BBUP was 46% to 51% across a 16-fold dose range, with dose-proportional increases in systemic exposure. Apparent steady-state conditions occurred within 3 days of dosing. These pharmacokinetic results suggest that therapeutic buprenorphine plasma concentrations can be obtained with BBUP across a wide dose range in a shorter time than other (eg, transdermal) dosage forms. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

SU-F-T-57: Delivered Activity Accuracy of Radium 223 Dichloride Injections, When Being Administrated for Castration Resistant Prostate Cancer, Symptomatic Bone Metastases. The Impact of Residual Activity in the Spent Syringe and Dispensing Accuracy of Ra 223

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jennings, G

Purpose: To quantify the delivered activity accuracy of Radium 223 dichloride injections, when being administrated for castration – resistant prostate cancer, symptomatic bone metastases. The impact of residual activity in the spent syringe and dispensing accuracy of Ra 223. Methods: The administration is by slow intravenous injection over 1 minute followed by double flushing of the 10 mL syringe and IV with saline. Eighty (80) procedures was used to investigate variations in the activity from the amount prescribed (µCi) = 1.35 × Patient weight Kg. The Activity dispensed into a 10mL syringe using a NIST traceable Capintec CRC-25R Chamber andmore » a cross calibrated capintec CRC-15R to measure activity in the syringe immediately before and after administration Results: The patients weight range from 121Ib to 235lb and doses ranging 74.25 µCi to 144.2 µCi. The deviation of dispensed dose vs Prescribed dose average +2.1% with a range of −1.1% to +5.7%. The Dose measured before administration ranges 79.3 µCi to 154.9 µCi. Deviation from the dispensed dose was show to average +2.9% with a range of −0.8% to +7.3%. The average residual dose post injection was 2.5 µCi or 2.2% of the pre injection activity. Ranging from 0.9 µCi to 6.2 µCi, 0.7% to 5.4% respectively. Subtracting the residual activity from that measured activity before injection and comparing it to prescription dose was shown to have an average variation of +2.7% with a range of −0.8% to 7.4%. Conclusion: The case resulted in the 6.2 µCi maximum residual dose had two syringes. A small, 82.8 µCi activity, case resulted in the 7.4% maximum variation in measures less residual verses prescription dose. The average +2.1 % dispenses activity of Ra 223 over the prescription dosage was seen to counteract the average 2.2% residual dosage found to remain in the syringe.« less

On the use of volumetric-modulated arc therapy for single-fraction thoracic vertebral metastases stereotactic body radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar, E-mail: damodar.pokhrel@uky.edu; Sood, Sumit; McClinton, Christopher

To retrospectively evaluate quality, efficiency, and delivery accuracy of volumetric-modulated arc therapy (VMAT) plans for single-fraction treatment of thoracic vertebral metastases using image-guided stereotactic body radiosurgery (SBRS) after RTOG 0631 dosimetric compliance criteria. After obtaining credentialing for MD Anderson spine phantom irradiation validation, 10 previously treated patients with thoracic vertebral metastases with noncoplanar hybrid arcs using 1 to 2 3D-conformal partial arcs plus 7 to 9 intensity-modulated radiation therapy beams were retrospectively re-optimized with VMAT using 3 full coplanar arcs. Tumors were located between T2 and T12. Contrast-enhanced T1/T2-weighted magnetic resonance images were coregistered with planning computed tomography and planningmore » target volumes (PTV) were between 14.4 and 230.1 cc (median = 38.0 cc). Prescription dose was 16 Gy in 1 fraction with 6 MV beams at Novalis-TX linear accelerator consisting of micro multileaf collimators. Each plan was assessed for target coverage using conformality index, the conformation number, the ratio of the volume receiving 50% of the prescription dose over PTV, R50%, homogeneity index (HI), and PTV-1600 coverage per RTOG 0631 requirements. Organs-at-risk doses were evaluated for maximum doses to spinal cord (D{sub 0.03} {sub cc}, D{sub 0.35} {sub cc}), partial spinal cord (D{sub 10%}), esophagus (D{sub 0.03} {sub cc} and D{sub 5} {sub cc}), heart (D{sub 0.03} {sub cc} and D{sub 15} {sub cc}), and lung (V{sub 5}, V{sub 10}, and maximum dose to 1000 cc of lung). Dose delivery efficiency and accuracy of each VMAT-SBRS plan were assessed using quality assurance (QA) plan on MapCHECK device. Total beam-on time was recorded during QA procedure, and a clinical gamma index (2%/2 mm and 3%/3 mm) was used to compare agreement between planned and measured doses. All 10 VMAT-SBRS plans met RTOG 0631 dosimetric requirements for PTV coverage. The plans demonstrated highly conformal and homogenous coverage of the vertebral PTV with mean HI, conformality index, conformation number, and R{sub 50%} values of 0.13 ± 0.03 (range: 0.09 to 0.18), 1.03 ± 0.04 (range: 0.98 to 1.09), 0.81 ± 0.06 (range: 0.72 to 0.89), and 4.2 ± 0.94 (range: 2.7 to 5.4), respectively. All 10 patients met protocol guidelines with maximum dose to spinal cord (average: 8.83 ± 1.9 Gy, range: 5.9 to 10.9 Gy); dose to 0.35 cc of spinal cord (average: 7.62 ± 1.7 Gy, range: 5.4 to 9.6 Gy); and dose to 10% of partial spinal cord (average 6.31 ± 1.5 Gy, range: 3.5 to 8.5 Gy) less than 14, 10, and 10 Gy, respectively. For all 10 patients, the maximum dose to esophagus (average: 9.41 ± 4.3 Gy, range: 1.5 to 14.9 Gy) and dose to 5 cc of esophagus (average: 7.43 ± 3.8 Gy, range: 1.1 to 11.8 Gy) were kept less than protocol requirements 16 Gy and 11.9 Gy, respectively. In a similar manner, all 10 patients met protocol compliance criteria with maximum dose to heart (average: 4.62 ± 3.5 Gy, range: 1.3 to 10.2 Gy) and dose to 15 cc of heart (average: 2.23 ± 1.8 Gy, range: 0.3 to 5.6 Gy) less than 22 and 16 Gy, respectively. The dose to the lung was retained much lower than protocol guidelines for all 10 patients. The total number of monitor units was, on average, 6919 ± 1187. The average beam-on time was 11.5 ± 2.0 minutes. The VMAT plans demonstrated dose delivery accuracy of 95.8 ± 0.7%, on average, for clinical gamma passing rate with 2%/2 mm criteria and 98.3 ± 0.8%, on average, with 3%/3 mm criteria. All VMAT-SBRS plans were considered clinically acceptable per RTOG 0631 dosimetric compliance criteria. VMAT planning provided highly conformal and homogenous dose distributions for the lower-dose vertebral PTV and the spinal cord as well as organs-at-risk such as esophagus, heart, and lung. Higher QA pass rates and shorter beam-on time suggest that VMAT-SBRS is a clinically feasible, fast, and effective treatment option for patients with thoracic vertebral metastases.« less

Chemical Dosimeter Tube With Coaxial Sensing Rod

NASA Technical Reports Server (NTRS)

Lueck, Dale E.

1993-01-01

Improved length-of-stain (LOS) chemical dosimeter indicates total dose of chemical vapor in air. Made with rods and tubes of various diameters to obtain various sensitivities and dynamic ranges. Sensitivity larger and dose range smaller when more room for diffusion in gap between tube and rod. Offers greater resistance to changing of color of exposed dye back to color of unexposed condition, greater sensitivity, and higher degree of repeatability. Developed to measure doses of gaseous HCI, dosimeter modified by use of other dyes to indicate doses of other chemical vapors.

Intra-oral colonization of macaque monkeys by Actinobacillus actinomycetemcomitans

PubMed Central

Beighton, David; Taichman, Norton S.; Simpson, David L.; Dirienzo, Joseph M.; Johnson, Newell W.

2012-01-01

Actinobacillus actinomycetemcomitans was acquired by captive Macaca fascicularis 3 to 6 months after birth, and all monkeys aged over 6 months harbored detectable levels. This microorganism was most frequently isolated from the gingival plaque of the incisor (and other) teeth compared with other oral sites. Strains were leukotoxic by bioassay and Western blot analysis. Antibodies in macaque serum contained neutralized the leukotoxin of a human A. actinomycetemcomitans strain. High titres of maternal neutralizing anti-leukotoxin antibodies were detected in neonates; the titre then fell rapidly so that by 6 months the antibody titer was zero. Antileukotoxin antibody production was detected after 6 months of age, rapidly reaching a high level within 2 years after birth. The presence of leukotoxic strains of A. actinomycetemcomitans in the gingival region did not appear to be correlated with an increase in susceptibility to periodontal disease. PMID:2628866

76 FR 677 - Requirements for Importers of Nonhuman Primates

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

...CDC is proposing to amend its regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs. Filovirus testing will continue to be required only for Old World NHPs. CDC also is proposing to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their registrations, (from every 180 days to every two years). CDC proposes to incorporate existing guidelines into the regulations and add new provisions to address: NHPs imported as part of a trained animal act; NHPs imported or transferred by zoological societies; The transfer of NHPs from approved laboratories; and Non-live imported NHP products. CDC is also proposing that all NHPs be imported only through ports of entry where a CDC quarantine station is located.

Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

PubMed

Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

2002-08-01

Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

Resolution of the African hominoid trichotomy by use of a mitochondrial gene sequence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruvolo, M.; Disotell, T.R.; Allard, M.W.

1991-02-15

Mitochondrial DNA sequences encoding the cytochrome oxidase subunit II gene have been determined for five primate species, siamang (Hylobates syndactylus), lowland gorilla (Gorilla gorilla), pygmy chimpanzee (Pan paniscus), crab-eating macaque (Macaca fascicularis), and green monkey (Cercopithecus aethiops), and compared with published sequences of other primate and nonprimate species. Comparisons of cytochrome oxidase subunit II gene sequences provide clear-cut evidence from the mitochondrial genome for the separation of the African ape trichotomy into two evolutionary lineages, one leading to gorillas and the other to humans and chimpanzees. Several different tree-building methods support this same phylogenetic tree topology. The comparisons also yieldmore » trees in which a substantial length separates the divergence point of gorillas from that of humans and chimpanzees, suggesting that the lineage most immediately ancestral to humans and chimpanzees may have been in existence for a relatively long time.« less

Human Exposure to Herpesvirus B–Seropositive Macaques, Bali, Indonesia

PubMed Central

Engel, Gregory A.; Schillaci, Michael A.; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

2002-01-01

Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a “monkey forest” (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B. PMID:12141963

Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox.

PubMed

Johnson, Reed F; Yellayi, Srikanth; Cann, Jennifer A; Johnson, Anthony; Smith, Alvin L; Paragas, Jason; Jahrling, Peter B; Blaney, Joseph E

2011-09-30

Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease within 12 days post-inoculation in two independent experiments. Clinical observations and hematological and histopathological findings support hemorrhagic disease. Cowpox virus replicated to high levels in blood (8.0-9.0 log(10) gene copies/mL) and tissues including lymph nodes, thymus, spleen, bone marrow, and lungs. This unique model of hemorrhagic orthopoxvirus infection provides an accessible means to further study orthopoxvirus pathogenesis and to identify virus-specific and nonspecific therapies. Such studies will serve to complement the existing nonhuman primate models of more classical poxviral disease. Published by Elsevier Inc.

Differential regulation of amyloid-. beta. -protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, G.A.; Lewis, D.A.; Bahmanyar, S.

1988-02-01

The authors have mapped the neuroanatomical distribution of amyloid-..beta..-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-..beta..-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In the central nervous system of monkey and normal aged human, image analysis shows that neurons of the dentate gyrus and cornu Ammonis fields contain a 2.5-times-greater hybridization signal than is present in neurons of the subiculum and entorhinal cortex. In contrast, in the Alzheimer disease hippocampal formation, the levels of amyloid-..beta..-protein mRNAmore » in the cornu Ammonis field 3 and parasubiculum are equivalent. These findings suggest that within certain neuronal subpopulations cell type-specific regulation of amyloid-..beta..-protein gene expression may be altered in Alzheimer disease.« less

Proton therapy of prostate cancer by anterior-oblique beams: implications of setup and anatomy variations

NASA Astrophysics Data System (ADS)

Moteabbed, M.; Trofimov, A.; Sharp, G. C.; Wang, Y.; Zietman, A. L.; Efstathiou, J. A.; Lu, H.-M.

2017-03-01

Proton therapy of prostate by anterior beams could offer an attractive option for treating patients with hip prosthesis and limiting the high-dose exposure to the rectum. We investigated the impact of setup and anatomy variations on the anterior-oblique (AO) proton plan dose, and strategies to manage these effects via range verification and adaptive delivery. Ten patients treated by bilateral (BL) passive-scattering proton therapy (79.2 Gy in 44 fractions) who underwent weekly verification CT scans were selected. Plans with AO beams were additionally created. To isolate the effect of daily variations, initial AO plans did not include range uncertainty margins. The use of fixed planning margins and adaptive range adjustments to manage these effects was investigated. For each case, the planned dose was recalculated on weekly CTs, and accumulated on the simulation CT using deformable registration to approximate the delivered dose. Planned and accumulated doses were compared for each scenario to quantify dose deviations induced by variations. The possibility of estimating the necessary range adjustments before each treatment was explored by simulating the procedure of a diode-based in vivo range verification technique, which would potentially be used clinically. The average planned rectum, penile bulb and femoral heads mean doses were smaller for initial AO compared to BL plans (by 8.3, 16.1 and 25.9 Gy, respectively). After considering interfractional variations in AO plans, the target coverage was substantially reduced. The maximum reduction of V 79.2/D 95/D mean/EUD for AO (without distal margins) (25.3%/10.7/1.6/4.9 Gy, respectively) was considerably larger than BL plans. The loss of coverage was mainly related to changes in water equivalent path length of the prostate after fiducial-based setup, caused by discrepancies in patient anterior surface and bony-anatomy alignment. Target coverage was recovered partially when using fixed planning margins, and fully when applying adaptive range adjustments. The accumulated organs-at-risk dose for AO beams after range adjustment demonstrated full sparing of femoral heads and superior sparing of penile bulb and rectum compared to the conventional BL cases. Our study indicates that using AO beams makes prostate treatment more susceptible to target underdose induced by interfractional variations. Adaptive range verification/adjustment may facilitate the use of anterior beam approaches, and ensure adequate target coverage in every fraction of the treatment.

Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

PubMed

Craven, Meghan; Frank, Graeme R

2018-06-27

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 μg/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. This study is a retrospective chart review of infants with CH between 2002 and 2012. Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12±2.5 μg/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthyroxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2±2.4, 11.5±2.1 and 10.3±2.6 μg/kg/day, respectively (p≤0.0001). Of the 34% of infants treated with an initial dose of >12.5 μg/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was ≤12.5 μg/kg/day (p=0.007). Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.

WE-AB-BRB-08: Progress Towards a 2D OSL Dosimetry System Using Al2O3:C Films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, M F; Yukihara, E; Schnell, E

Purpose: To develop a 2D dosimetry system based on the optically stimulated luminescence (OSL) of Al{sub 2}O{sub 3}:C films for medical applications. Methods: A 2D laser scanning OSL reader was built for readout of newly developed Al2O3:C films (Landauer Inc.). An image reconstruction algorithm was developed to correct for inherent effects introduced by reader design and detector properties. The system was tested using irradiations with photon and carbon ion beams. A calibration was obtained using a 6 MV photon beam from clinical accelerator and the dose measurement precision was tested using a range of doses and different dose distributions (flatmore » field and wedge field). The dynamic range and performance of the system in the presence of large dose gradients was also tested using 430 MeV/u {sup 12}C single and multiple pencil beams. All irradiations were performed with Gafchromic EBT3 film for comparison. Results: Preliminary results demonstrate a near-linear OSL dose response to photon fields and the ability to measure dose in dose distributions such as flat field and wedge field. Tests using {sup 12}C pencil beam demonstrate ability to measure doses over four orders of magnitude. The dose profiles measured by the OSL film generally agreed well with that measured by the EBT3 film. The OSL image signal-to-noise ratio obtained in the current conditions require further improvement. On the other hand, EBT3 films had large uncertainties in the low dose region due to film-to-film or intra-film variation in the background. Conclusion: A 2D OSL dosimetry system was developed and initial tests have demonstrated a wide dynamic range as well as good agreement between the delivered and measured doses. The low background, wide dynamic range and wide range of linearity in dose response observed for the Al{sub 2}O{sub 3}:C OSL film can be beneficial for dosimetry in radiation therapy applications, especially for small field dosimetry. This work has been funded by Landauer Inc. Dr. Eduardo G. Yukihara also would like to thank the Alexander von Humboldt Foundation for his support at the DKFZ.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, J; Zhang, W; Lu, J

Purpose: To investigate the accuracy and feasibility of dose calculations using kilovoltage cone beam computed tomography in cervical cancer radiotherapy using a correction algorithm. Methods: The Hounsfield units (HU) and electron density (HU-density) curve was obtained for both planning CT (pCT) and kilovoltage cone beam CT (CBCT) using a CIRS-062 calibration phantom. The pCT and kV-CBCT images have different HU values, and if the HU-density curve of CBCT was directly used to calculate dose in CBCT images may have a deviation on dose distribution. It is necessary to normalize the different HU values between pCT and CBCT. A HU correctionmore » algorithm was used for CBCT images (cCBCT). Fifteen intensity-modulated radiation therapy (IMRT) plans of cervical cancer were chosen, and the plans were transferred to the pCT and cCBCT data sets without any changes for dose calculations. Phantom and patient studies were carried out. The dose differences and dose distributions were compared between cCBCT plan and pCT plan. Results: The HU number of CBCT was measured by several times, and the maximum change was less than 2%. To compare with pCT, the CBCT and cCBCT has a discrepancy, the dose differences in CBCT and cCBCT images were 2.48%±0.65% (range: 1.3%∼3.8%) and 0.48%±0.21% (range: 0.1%∼0.82%) for phantom study, respectively. For dose calculation in patient images, the dose differences were 2.25%±0.43% (range: 1.4%∼3.4%) and 0.63%±0.35% (range: 0.13%∼0.97%), respectively. And for the dose distributions, the passing rate of cCBCT was higher than the CBCTs. Conclusion: The CBCT image for dose calculation is feasible in cervical cancer radiotherapy, and the correction algorithm offers acceptable accuracy. It will become a useful tool for adaptive radiation therapy.« less

Estimation of organ and effective doses from newborn radiography of the chest and abdomen.

PubMed

Ma, Hillgan; Elbakri, Idris A; Reed, Martin

2013-09-01

Neonatal intensive care patients undergo frequent chest and abdomen radiographic imaging. In this study, the organ doses and the effective dose resulting from combined chest-abdomen radiography of the newborn child are determined. These values are calculated using the Monte Carlo simulation software PCXCM 2.0 and compared with direct dose measurements obtained from thermoluminescent detectors (TLDs) in a physical phantom. The effective dose obtained from PCXMC is 21.2 ± 0.7 μSv and that obtained from TLD measurements is 22.0 ± 0.5 μSv. While the two methods are in close agreement with regard to the effective dose, there is a wide range of variation in organ doses, ranging from 85 % difference for the testes to 1.4 % for the lungs. Large organ dose variations are attributed to organs at the edge of the field of view, or organs with large experimental error or simulation uncertainty. This study suggests that PCXMC can be used to estimate organ and effective doses for newborn patients.

A dose ranging study of ibuprofen suspension as an antipyretic.

PubMed Central

Marriott, S C; Stephenson, T J; Hull, D; Pownall, R; Smith, C M; Butler, A

1991-01-01

A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic. PMID:1929509

Energy spectrum control for modulated proton beams.

PubMed

Hsi, Wen C; Moyers, Michael F; Nichiporov, Dmitri; Anferov, Vladimir; Wolanski, Mark; Allgower, Chris E; Farr, Jonathan B; Mascia, Anthony E; Schreuder, Andries N

2009-06-01

In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.

Nectin-4 Interactions Govern Measles Virus Virulence in a New Model of Pathogenesis, the Squirrel Monkey (Saimiri sciureus).

PubMed

Delpeut, Sébastien; Sawatsky, Bevan; Wong, Xiao-Xiang; Frenzke, Marie; Cattaneo, Roberto; von Messling, Veronika

2017-06-01

In addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (MeV) infection. Disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain New World monkey species. To investigate if squirrel monkeys ( Saimiri sciureus ), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutics, we infected them with a green fluorescent protein-expressing MeV. Compared to cynomolgus macaques ( Macaca fascicularis ) infected with the same virus, the squirrel monkeys developed more-severe immunosuppression, higher viral load, and a broader range of clinical signs typical for measles. In contrast, infection with an MeV unable to interact with the epithelial receptor nectin-4, while causing immunosuppression, resulted in only a mild and transient rash and a short-lived elevation of the body temperature. Similar titers of the wild-type and nectin-4-blind MeV were detected in peripheral blood mononuclear cells and lymph node homogenates, but only the wild-type virus was found in tracheal lavage fluids and urine. Thus, our study demonstrates the importance of MeV interactions with nectin-4 for clinical disease in the new and better-performing S. sciureus model of measles pathogenesis. IMPORTANCE The characterization of mechanisms underlying measles virus clinical disease has been hampered by the lack of an animal model that reproduces the course of disease seen in human patients. Here, we report that infection of squirrel monkeys ( Saimiri sciureus ) fulfills these requirements. Comparative infection with wild-type and epithelial cell receptor-blind viruses demonstrated the importance of epithelial cell infection for clinical disease, highlighting the spread to epithelia as an attractive target for therapeutic strategies. Copyright © 2017 American Society for Microbiology.

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

Clinical Decision Support Improves Initial Dosing and Monitoring of Tobramycin and Amikacin

PubMed Central

Cox, Zachary L.; Nelsen, Cori L.; Waitman, Lemuel R.; McCoy, Jacob A.; Peterson, Josh F.

2010-01-01

Purpose Clinical decision support (CDS) systems could be valuable tools in reducing aminoglycoside prescribing errors. We evaluated the impact of CDS on initial dosing, interval, and pharmacokinetic outcomes of amikacin and tobramycin therapy. Methods A complex CDS advisor to provide guidance on initial dosing and monitoring, using both traditional and extended interval dosing strategies, was integrated into computerized provider order entry (CPOE) and compared to a control group which featured close pharmacy monitoring of all aminoglycoside orders. A random sample of 118 patients from an academic, tertiary care medical center prescribed amikacin and tobramycin prior to advisor implementation was compared to 98 patients admitted following advisor implementation. Primary outcome was an initial dose within 10% of a dose calculated to be adherent to published dose guidelines. Secondary outcomes were a guideline-adherent interval, trough and peak concentrations in goal range, and incidence of nephrotoxicity. Results Of 216 patients studied, 97 were prescribed amikacin and 119 were prescribed tobramycin. The primary outcome of initial dosing consistent with guideline-based care increased from 40% in the pre-advisor arm to 80% in the post-advisor arm (p<0.001), with a number needed to treat of 3 patients to prevent one incorrect dose. Correct initial interval based on renal function also increased from 63% to 87% (p<0.001). The changes in initial dosing and interval resulted in an increase of trough concentrations in the goal range from 59% pre-advisor to 89% post-advisor implementation (p=0.0004). There was no significant difference in peak concentrations in goal range or incidence of nephrotoxicity (25% vs. 17%, p=0.2). Conclusion An advisor for aminoglycoside dosing and monitoring integrated into CPOE significantly improves initial dosing, selection of interval, and trough concentrations at goal compared to unassisted physician dosing. PMID:21411805

Range-Finding Risk Assessment of Inhalation Exposure to Nanodiamonds in a Laboratory Environment

PubMed Central

Koivisto, Antti J.; Palomäki, Jaana E.; Viitanen, Anna-Kaisa; Siivola, Kirsi M.; Koponen, Ismo K.; Yu, Mingzhou; Kanerva, Tomi S.; Norppa, Hannu; Alenius, Harri T.; Hussein, Tareq; Savolainen, Kai M.; Hämeri, Kaarle J.

2014-01-01

This study considers fundamental methods in occupational risk assessment of exposure to airborne engineered nanomaterials. We discuss characterization of particle emissions, exposure assessment, hazard assessment with in vitro studies, and risk range characterization using calculated inhaled doses and dose-response translated to humans from in vitro studies. Here, the methods were utilized to assess workers’ risk range of inhalation exposure to nanodiamonds (NDs) during handling and sieving of ND powder. NDs were agglomerated to over 500 nm particles, and mean exposure levels of different work tasks varied from 0.24 to 4.96 µg·m−3 (0.08 to 0.74 cm−3). In vitro-experiments suggested that ND exposure may cause a risk for activation of inflammatory cascade. However, risk range characterization based on in vitro dose-response was not performed because accurate assessment of delivered (settled) dose on the cells was not possible. Comparison of ND exposure with common pollutants revealed that ND exposure was below 5 μg·m−3, which is one of the proposed exposure limits for diesel particulate matter, and the workers’ calculated dose of NDs during the measurement day was 74 ng which corresponded to 0.02% of the modeled daily (24 h) dose of submicrometer urban air particles. PMID:24840353

Oral desmopressin in central diabetes insipidus.

PubMed Central

Westgren, U; Wittström, C; Harris, A S

1986-01-01

Seven paediatric patients with central diabetes insipidus were studied in an open dose ranging study in hospital followed by a six month study on an outpatient basis to assess the efficacy and safety of peroral administration of DDAVP (desmopressin) tablets. In the dose ranging study a dose dependent antidiuretic response was observed. The response to 12.5-50 mcg was, however, less effective in correcting baseline polyuria than were doses of 100 mcg and above. Patients were discharged from hospital on a preliminary dosage regimen ranging from 100 to 400 mcg three times daily. After an initial adjustment in dosage in three patients at one week follow up, all patients were stabilised on treatment with tablets and reported an adequate water turnover at six months. As with the intranasal route of administration dosage requirements varied from patient to patient, and a dose range rather than standard doses were required. A significant correlation, however, was found for the relation between previous intranasal and present oral daily dosage. No adverse reactions were reported. No clinically significant changes were noted in blood chemistry and urinalysis. All patients expressed a preference for the oral over existing intranasal treatment. Treatment with tablets offers a beneficial alternative to the intranasal route, particularly in patients with chronic rhinitis or impaired vision. PMID:3963868

Effect of processor temperature on film dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Shiv P.; Das, Indra J., E-mail: idas@iupui.edu

2012-07-01

Optical density (OD) of a radiographic film plays an important role in radiation dosimetry, which depends on various parameters, including beam energy, depth, field size, film batch, dose, dose rate, air film interface, postexposure processing time, and temperature of the processor. Most of these parameters have been studied for Kodak XV and extended dose range (EDR) films used in radiation oncology. There is very limited information on processor temperature, which is investigated in this study. Multiple XV and EDR films were exposed in the reference condition (d{sub max.}, 10 Multiplication-Sign 10 cm{sup 2}, 100 cm) to a given dose. Anmore » automatic film processor (X-Omat 5000) was used for processing films. The temperature of the processor was adjusted manually with increasing temperature. At each temperature, a set of films was processed to evaluate OD at a given dose. For both films, OD is a linear function of processor temperature in the range of 29.4-40.6 Degree-Sign C (85-105 Degree-Sign F) for various dose ranges. The changes in processor temperature are directly related to the dose by a quadratic function. A simple linear equation is provided for the changes in OD vs. processor temperature, which could be used for correcting dose in radiation dosimetry when film is used.« less

Dosimetry investigation of MOSFET for clinical IMRT dose verification.

PubMed

Deshpande, Sudesh; Kumar, Rajesh; Ghadi, Yogesh; Neharu, R M; Kannan, V

2013-06-01

In IMRT, patient-specific dose verification is followed regularly at each centre. Simple and efficient dosimetry techniques play a very important role in routine clinical dosimetry QA. The MOSFET dosimeter offers several advantages over the conventional dosimeters such as its small detector size, immediate readout, immediate reuse, multiple point dose measurements. To use the MOSFET as routine clinical dosimetry system for pre-treatment dose verification in IMRT, a comprehensive set of experiments has been conducted, to investigate its linearity, reproducibility, dose rate effect and angular dependence for 6 MV x-ray beam. The MOSFETs shows a linear response with linearity coefficient of 0.992 for a dose range of 35 cGy to 427 cGy. The reproducibility of the MOSFET was measured by irradiating the MOSFET for ten consecutive irradiations in the dose range of 35 cGy to 427 cGy. The measured reproducibility of MOSFET was found to be within 4% up to 70 cGy and within 1.4% above 70 cGy. The dose rate effect on the MOSFET was investigated in the dose rate range 100 MU/min to 600 MU/min. The response of the MOSFET varies from -1.7% to 2.1%. The angular responses of the MOSFETs were measured at 10 degrees intervals from 90 to 270 degrees in an anticlockwise direction and normalized at gantry angle zero and it was found to be in the range of 0.98 ± 0.014 to 1.01 ± 0.014. The MOSFETs were calibrated in a phantom which was later used for IMRT verification. The measured calibration coefficients were found to be 1 mV/cGy and 2.995 mV/cGy in standard and high sensitivity mode respectively. The MOSFETs were used for pre-treatment dose verification in IMRT. Nine dosimeters were used for each patient to measure the dose in different plane. The average variation between calculated and measured dose at any location was within 3%. Dose verification using MOSFET and IMRT phantom was found to quick and efficient and well suited for a busy radiotherapy department.

The Impact of Azilsartan Medoxomil Treatment (Capsule Formulation) at Doses Ranging From 10 to 80 mg: Significant, Rapid Reductions in Clinic Diastolic and Systolic Blood Pressure.

PubMed

Perez, Alfonso; Cao, Charlie

2017-03-01

In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d. ©2016 Wiley Periodicals, Inc.

Electron paramagnetic resonance (EPR) dosimetry using lithium formate in radiotherapy: comparison with thermoluminescence (TL) dosimetry using lithium fluoride rods.

PubMed

Vestad, Tor Arne; Malinen, Eirik; Olsen, Dag Rune; Hole, Eli Olaug; Sagstuen, Einar

2004-10-21

Solid-state radiation dosimetry by electron paramagnetic resonance (EPR) spectroscopy and thermoluminescence (TL) was utilized for the determination of absorbed doses in the range of 0.5-2.5 Gy. The dosimeter materials used were lithium formate and lithium fluoride (TLD-100 rods) for EPR dosimetry and TL dosimetry, respectively. 60Co gamma-rays and 4, 6, 10 and 15 MV x-rays were employed. The main objectives were to compare the variation in dosimeter reading of the respective dosimetry systems and to determine the photon energy dependence of the two dosimeter materials. The EPR dosimeter sensitivity was constant over the dose range in question, while the TL sensitivity increased by more than 5% from 0.5 to 2.5 Gy, thus displaying a supralinear dose response. The average relative standard deviation in the dosimeter reading per dose was 3.0% and 1.2% for the EPR and TL procedures, respectively. For EPR dosimeters, the relative standard deviation declined significantly from 4.3% to 1.1% over the dose range in question. The dose-to-water energy response for the megavoltage x-ray beams relative to 60Co gamma-rays was in the range of 0.990-0.979 and 0.984-0.962 for lithium formate and lithium fluoride, respectively. The results show that EPR dosimetry with lithium formate provides dose estimates with a precision comparable to that of TL dosimetry (using lithium fluoride) for doses above 2 Gy, and that lithium formate is slightly less dependent on megavoltage photon beam energy than lithium fluoride.

Electron paramagnetic resonance (EPR) dosimetry using lithium formate in radiotherapy: comparison with thermoluminescence (TL) dosimetry using lithium fluoride rods

NASA Astrophysics Data System (ADS)

Vestad, Tor Arne; Malinen, Eirik; Rune Olsen, Dag; Olaug Hole, Eli; Sagstuen, Einar

2004-10-01

Solid-state radiation dosimetry by electron paramagnetic resonance (EPR) spectroscopy and thermoluminescence (TL) was utilized for the determination of absorbed doses in the range of 0.5-2.5 Gy. The dosimeter materials used were lithium formate and lithium fluoride (TLD-100 rods) for EPR dosimetry and TL dosimetry, respectively. 60Co ggr-rays and 4, 6, 10 and 15 MV x-rays were employed. The main objectives were to compare the variation in dosimeter reading of the respective dosimetry systems and to determine the photon energy dependence of the two dosimeter materials. The EPR dosimeter sensitivity was constant over the dose range in question, while the TL sensitivity increased by more than 5% from 0.5 to 2.5 Gy, thus displaying a supralinear dose response. The average relative standard deviation in the dosimeter reading per dose was 3.0% and 1.2% for the EPR and TL procedures, respectively. For EPR dosimeters, the relative standard deviation declined significantly from 4.3% to 1.1% over the dose range in question. The dose-to-water energy response for the megavoltage x-ray beams relative to 60Co ggr-rays was in the range of 0.990-0.979 and 0.984-0.962 for lithium formate and lithium fluoride, respectively. The results show that EPR dosimetry with lithium formate provides dose estimates with a precision comparable to that of TL dosimetry (using lithium fluoride) for doses above 2 Gy, and that lithium formate is slightly less dependent on megavoltage photon beam energy than lithium fluoride.

Effect of proton irradiation dose on InAlN/GaN metal-oxide semiconductor high electron mobility transistors with Al 2O 3 gate oxide

DOE PAGES

Ahn, Shihyun; Kim, Byung -Jae; Lin, Yi -Hsuan; ...

2016-07-26

The effects of proton irradiation on the dc performance of InAlN/GaN metal-oxide-semiconductor high electron mobility transistors (MOSHEMTs) with Al 2O 3 as the gate oxide were investigated. The InAlN/GaN MOSHEMTs were irradiated with doses ranging from 1×10 13 to 1×10 15cm –2 at a fixed energy of 5MeV. There was minimal damage induced in the two dimensional electron gas at the lowest irradiation dose with no measurable increase in sheet resistance, whereas a 9.7% increase of the sheet resistance was observed at the highest irradiation dose. By sharp contrast, all irradiation doses created more severe degradation in the Ohmic metalmore » contacts, with increases of specific contact resistance from 54% to 114% over the range of doses investigated. These resulted in source-drain current–voltage decreases ranging from 96 to 242 mA/mm over this dose range. The trap density determined from temperature dependent drain current subthreshold swing measurements increased from 1.6 × 10 13 cm –2 V –1 for the reference MOSHEMTs to 6.7 × 10 13 cm –2 V –1 for devices irradiated with the highest dose. In conclusion, the carrier removal rate was 1287 ± 64 cm –1, higher than the authors previously observed in AlGaN/GaN MOSHEMTs for the same proton energy and consistent with the lower average bond energy of the InAlN.« less

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

PubMed

Broome, E J; Brown, D L; Mitchel, R E J

2002-08-01

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.

Use of Microdosing and Accelerator Mass Spectrometry To Evaluate the Pharmacokinetic Linearity of a Novel Tricyclic GyrB/ParE Inhibitor in Rats

PubMed Central

Lao, Victoria; Ramos, Courtney L.; Ong, Voon S.; Turteltaub, Kenneth W.

2014-01-01

Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a 14C-labeled microdose versus a 14C-labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng · h/ml and 1,336 ng · h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng · h/ml for the microdose and 418.2 ng · h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals. PMID:25136019

SU-E-T-135: Investigation of Commercial-Grade Flatbed Scanners and a Medical- Grade Scanner for Radiochromic EBT Film Dosimetry.

PubMed

Syh, J; Patel, B; Syh, J; Wu, H; Rosen, L; Durci, M; Katz, S; Sibata, C

2012-06-01

To evaluate the characteristics of commercial-grade flatbed scanners and medical-grade scanners for radiochromic EBT film dosimetry. Performance aspects of a Vidar Dosimetry Pro Advantage (Red), Epson 750 Pro, Microtek ArtixScan 1800f, and Microtek ScanMaker 8700 scanner for EBT2 Gafchromic film were evaluated in the categories of repeatability, maximum distinguishable optical density (OD) differentiation, OD variance, and dose curve characteristics. OD step film by Stouffer Industries containing 31 steps ranging from 0.05 to 3.62 OD was used. EBT films were irradiated with dose ranging from 20 to 600 cGy in 6×6 cm 2 field sizes and analyzed 24 hours later using RIT113 and Tomotherapy Film Analyzer software. Scans were performed in transmissive mode, landscape orientation, 16-bit image. The mean and standard deviation Analog to Digital (A/D) scanner value was measured by selecting a 3×3 mm 2 uniform area in the central region of each OD step from a total of 20 scans performed over several weeks. Repeatability was determined from the variance of OD step 0.38. Maximum distinguishable OD was defined as the last OD step whose range of A/D values does not overlap with its neighboring step. Repeatability uncertainty ranged from 0.1% for Vidar to 4% for Epson. Average standard deviation of OD steps ranged from 0.21% for Vidar to 6.4% for ArtixScan 1800f. Maximum distinguishable optical density ranged from 3.38 for Vidar to 1.32 for ScanMaker 8700. A/D range of each OD step corresponds to a dose range. Dose ranges of OD steps varied from 1% for Vidar to 20% for ScanMaker 8700. The Vidar exhibited a dose curve that utilized a broader range of OD values than the other scanners. Vidar exhibited higher maximum distinguishable OD, smaller variance in repeatability, smaller A/D value deviation per OD step, and a shallower dose curve with respect to OD. © 2012 American Association of Physicists in Medicine.

Postsacral vertebral morphology in relation to tail length among primates and other mammals.

PubMed

Russo, Gabrielle A

2015-02-01

Tail reduction/loss independently evolved in a number of mammalian lineages, including hominoid primates. One prerequisite to appropriately contextualizing its occurrence and understanding its significance is the ability to track evolutionary changes in tail length throughout the fossil record. However, to date, the bony correlates of tail length variation among living taxa have not been comprehensively examined. This study quantifies postsacral vertebral morphology among living primates and other mammals known to differ in relative tail length (RTL). Linear and angular measurements with known biomechanical significance were collected on the first, mid-, and transition proximal postsacral vertebrae, and their relationship with RTL was assessed using phylogenetic generalized least-squares regression methods. Compared to shorter-tailed primates, longer-tailed primates possess a greater number of postsacral vertebral features associated with increased proximal tail flexibility (e.g., craniocaudally longer vertebral bodies), increased intervertebral body joint range of motion (e.g., more circularly shaped cranial articular surfaces), and increased leverage of tail musculature (e.g., longer spinous processes). These observations are corroborated by the comparative mammalian sample, which shows that distantly related short-tailed (e.g., Phascolarctos, Lynx) and long-tailed (e.g., Dendrolagus, Acinonyx) nonprimate mammals morphologically converge with short-tailed (e.g., Macaca tonkeana) and long-tailed (e.g., Macaca fascicularis) primates, respectively. Multivariate models demonstrate that the variables examined account for 70% (all mammals) to 94% (only primates) of the variance in RTL. Results of this study may be used to infer the tail lengths of extinct primates and other mammals, thereby improving our understanding about the evolution of tail reduction/loss. © 2014 Wiley Periodicals, Inc.

Properties of cerebellar fastigial neurons during translation, rotation, and eye movements

NASA Technical Reports Server (NTRS)

Shaikh, Aasef G.; Ghasia, Fatema F.; Dickman, J. David; Angelaki, Dora E.

2005-01-01

The most medial of the deep cerebellar nuclei, the fastigial nucleus (FN), receives sensory vestibular information and direct inhibition from the cerebellar vermis. We investigated the signal processing in the primate FN by recording single-unit activities during translational motion, rotational motion, and eye movements. Firing rate modulation during horizontal plane translation in the absence of eye movements was observed in all non-eye-movement-sensitive cells and 26% of the pursuit eye-movement-sensitive neurons in the caudal FN. Many non-eye-movement-sensitive cells recorded in the rostral FN of three fascicularis monkeys exhibited convergence of signals from both the otolith organs and the semicircular canals. At low frequencies of translation, the majority of these rostral FN cells changed their firing rates in phase with head velocity rather than linear acceleration. As frequency increased, FN vestibular neurons exhibited a wide range of response dynamics with most cells being characterized by increasing phase leads as a function of frequency. Unlike cells in the vestibular nuclei, none of the rostral FN cells responded to rotational motion alone, without simultaneously exhibiting sensitivity to translational motion. Modulation during earth-horizontal axis rotation was observed in more than half (77%) of the neurons, although with smaller gains than during translation. In contrast, only 47% of the cells changed their firing rates during earth-vertical axis rotations in the absence of a dynamic linear acceleration stimulus. These response properties suggest that the rostral FN represents a main processing center of otolith-driven information for inertial motion detection and spatial orientation.

Developing a musculoskeletal model of the primate skull: predicting muscle activations, bite force, and joint reaction forces using multibody dynamics analysis and advanced optimisation methods.

PubMed

Shi, Junfen; Curtis, Neil; Fitton, Laura C; O'Higgins, Paul; Fagan, Michael J

2012-10-07

An accurate, dynamic, functional model of the skull that can be used to predict muscle forces, bite forces, and joint reaction forces would have many uses across a broad range of disciplines. One major issue however with musculoskeletal analyses is that of muscle activation pattern indeterminacy. A very large number of possible muscle force combinations will satisfy a particular functional task. This makes predicting physiological muscle recruitment patterns difficult. Here we describe in detail the process of development of a complex multibody computer model of a primate skull (Macaca fascicularis), that aims to predict muscle recruitment patterns during biting. Using optimisation criteria based on minimisation of muscle stress we predict working to balancing side muscle force ratios, peak bite forces, and joint reaction forces during unilateral biting. Validation of such models is problematic; however we have shown comparable working to balancing muscle activity and TMJ reaction ratios during biting to those observed in vivo and that peak predicted bite forces compare well to published experimental data. To our knowledge the complexity of the musculoskeletal model is greater than any previously reported for a primate. This complexity, when compared to more simple representations provides more nuanced insights into the functioning of masticatory muscles. Thus, we have shown muscle activity to vary throughout individual muscle groups, which enables them to function optimally during specific masticatory tasks. This model will be utilised in future studies into the functioning of the masticatory apparatus. Copyright © 2012 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate XVMC computed rib doses for peripherally located non-small-cell-lung tumors treated with SBRT following RTOG-0915 guidelines. Methods: Twenty patients with solitary peripherally located non-small-cell-lung tumors were treated using XVMC-based SBRT to 50–54Gy in 5−3 fractions, respectively, for PTV(V100%)=95%. Based on 4D-CT, ITV was delineated on MaximumIP images and organs-at-risk(OARs) including ribs were contoured on MeanIP images. Mean PTV(ITV+5mm uniform margin) was 46.1±38.7cc (range, 11.1–163.0cc). XVMC SBRT treatment plans were generated with a combination of non-coplanar 3D-conformal arcs/beams, and were delivered by Novalis-TX consisting of HD-MLCs and a 6MV-SRS(1000MU/min) beam, following RTOG-0915 criteria. XVMC rib maximum dose and dosemore » to <1cc, <5cc, <10cc were evaluated as a function of PTV, prescription dose and 3D-distance from tumor isocenter to the most proximal rib contour. Plans were re-computed using heterogeneity-corrected pencil-beam (PB-hete) algorithm utilizing identical beam geometry/MLC positions and MUs and subsequently compared to XVMC. Results: XVMC average maximum rib dose was 50.9±6.4Gy (range, 35.1–59.3Gy). XVMC mean rib dose to <1cc was 41.6±5.6Gy (range, 27.9–47.9Gy), <5cc was 31.2±7.3Gy (range, 10.6–43.1Gy), and <10cc was 21.2±8.7Gy (range, 1.1–36Gy), respectively. For the given prescription, correlation between PTV and rib doses to <5cc (p=0.005) and <10cc (p=0.018) was observed. 3D-distance from the tumor isocenter to the proximal rib contour strongly correlated with maximum rib dose (p=0.0001). PB-hete algorithm overestimated maximum rib dose and dose to <1cc, <5cc, and <10cc of ribs by 5%, 3%, 3%, and 3%, respectively. Conclusion: PB-hete overestimates ribs dose relative to XVMC. Since all the clinical XVMC plans were generated without compromising the target coverage (per RTOG-0915), almost all patient’s ribs doses were higher than the protocol guidelines. As expected, larger tumor size and proximity to ribs received higher absolute dose to ribs. Prospective observation is needed to determine if XVMC delivered rib doses correlates with patient symptoms including chest wall pain and/or rib fractures.« less

EPR TOOTH DOSIMETRY OF SNTS AREA INHABITANTS

PubMed Central

Sholom, Sergey; Desrosiers, Marc; Bouville, André; Luckyanov, Nicholas; Chumak, Vadim

2009-01-01

The determination of external dose to teeth of inhabitants of settlements near the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry technique to assess radiation doses associated with exposure to radioactive fallout from the test site. In this study, tooth doses have been reconstructed for 103 persons with all studied teeth having been formed before the first nuclear test in 1949. Doses above those received from natural background radiation, termed “accident doses”, were found to lie in the range from zero to approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk city was approximately 9 Gy. The variability of reconstructed doses within each of the settlements demonstrated heterogeneity of the deposited fallout as well as variations in lifestyle. The village mean external gamma doses for residents of nine[ settlements were in the range from a few tens of mGy to approximately 100 mGy. PMID:19590746

Cytogenetic effect of low dose gamma-radiation in Hordeum vulgare seedlings: non-linear dose-effect relationship.

PubMed

Geras'kin, Stanislav A; Oudalova, Alla A; Kim, Jin Kyu; Dikarev, Vladimir G; Dikareva, Nina S

2007-03-01

The induction of chromosome aberrations in Hordeum vulgare germinated seeds was studied after ionizing irradiation with doses in the range of 10-1,000 mGy. The relationship between the frequency of aberrant cells and the absorbed dose was found to be nonlinear. A dose-independent plateau in the dose range from about 50 to 500 mGy was observed, where the level of cytogenetic damage was significantly different from the spontaneous level. The comparison of the goodness of the experimental data fitting with mathematical models of different complexity, using the most common quantitative criteria, demonstrated the advantage of a piecewise linear model over linear and polynomial models in approximating the frequency of cytogenetical disturbances. The results of the study support the hypothesis of indirect mechanisms of mutagenesis induced by low doses. Fundamental and applied implications of these findings are discussed.

Derivation of a reference dose for a complex petroleum hydrocarbon mixture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryer-Powder, J.E.; LaPirre, A.; Scofield, R.

1997-12-31

Petroleum hydrocarbon mixtures pose a challenge in assessing potential health effects associated with environmental exposures through impacted media. Two components of risk assessment that must be addressed when evaluating these mixtures are toxicity and environmental fate. In this paper, we focus on issues regarding toxicity. Specifically, we have developed a methodology to derive a reference dose (RfD) for a complex petroleum hydrocarbon mixture referred to as diluent. Diluent is a solvent used in the production of crude oil and is composed of hydrocarbons in the middle distillate range. Two conservative approaches to developing a reference dose for diluent are presented.more » Both involve separating the diluent into carbon number ranges (e.g., diluent consists of hydrocarbons containing between 5 carbons and greater than 21 carbons, so, the mixture can be divided into mixtures of hydrocarbons having 5 carbons, 6-11 carbons, etcetera) and assigning each range a representative RfD. In the first approach, the representative RfD for each range is that of one specific chemical within the range (e.g., the reference dose for the C{sub 5}-C{sub 8} carbon range is that of n-hexane). In the second approach, the RfD dose for each range is that of a mixture of chemicals representative of each carbon number range (e.g., the RfD for the C{sub 6} to C{sub 11} carbon range is that of mineral spirits). The RfD for each carbon range is then multiplied by the percent of diluent in the corresponding range and the products are added to arrive at a final RfD. The RfD for diluent using the first approach is estimated at 2 mg/kg-day and that using the second approach is estimated at 1 mg/kg-day.« less

Four-dimensional layer-stacking carbon-ion beam dose distribution by use of a lung numeric phantom.

PubMed

Mori, Shinichiro; Kumagai, Motoki; Miki, Kentaro

2015-07-01

To extend layer-stacking irradiation to accommodate intrafractional organ motion, we evaluated the carbon-ion layer-stacking dose distribution using a numeric lung phantom. We designed several types of range compensators. The planning target volume was calculated from the respective respiratory phases for consideration of intrafractional beam range variation. The accumulated dose distribution was calculated by registering of the dose distributions at respective phases to that at the reference phase. We evaluated the dose distribution based on the following six parameters: motion displacement, direction, gating window, respiratory cycle, range-shifter change time, and prescribed dose. All parameters affected the dose conformation to the moving target. By shortening of the gating window, dose metrics for superior-inferior (SI) and anterior-posterior (AP) motions were decreased from a D95 of 94 %, Dmax of 108 %, and homogeneity index (HI) of 23 % at T00-T90, to a D95 of 93 %, Dmax of 102 %, and HI of 20 % at T40-T60. In contrast, all dose metrics except the HI were independent of respiratory cycle. All dose metrics in SI motion were almost the same in respective motion displacement, with a D95 of 94 %, Dmax of 108 %, Dmin of 89 %, and HI of 23 % for the ungated phase, and D95 of 93 %, Dmax of 102 %, Dmin of 85 %, and HI of 20 % for the gated phase. The dose conformation to a moving target was improved by the gating strategy and by an increase in the prescribed dose. A combination of these approaches is a practical means of adding them to existing treatment protocols without modifications.

Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

PubMed

Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

2014-04-01

Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

Degradation of the Bragg peak due to inhomogeneities.

PubMed

Urie, M; Goitein, M; Holley, W R; Chen, G T

1986-01-01

The rapid fall-off of dose at the end of range of heavy charged particle beams has the potential in therapeutic applications of sparing critical structures just distal to the target volume. Here we explored the effects of highly inhomogeneous regions on this desirable depth-dose characteristic. The proton depth-dose distribution behind a lucite-air interface parallel to the beam was bimodal, indicating the presence of two groups of protons with different residual ranges, creating a step-like depth-dose distribution at the end of range. The residual ranges became more spread out as the interface was angled at 3 degrees, and still more at 6 degrees, to the direction of the beam. A second experiment showed little significant effect on the distal depth-dose of protons having passed through a mosaic of teflon and lucite. Anatomic studies demonstrated significant effects of complex fine inhomogeneities on the end of range characteristics. Monoenergetic protons passing through the petrous ridges and mastoid air cells in the base of skull showed a dramatic degradation of the distal Bragg peak. In beams with spread out Bragg peaks passing through regions of the base of skull, the distal fall-off from 90 to 20% dose was increased from its nominal 6 to well over 32 mm. Heavy ions showed a corresponding degradation in their ends of range. In the worst case in the base of skull region, a monoenergetic neon beam showed a broadening of the full width at half maximum of the Bragg peak to over 15 mm (compared with 4 mm in a homogeneous unit density medium). A similar effect was found with carbon ions in the abdomen, where the full width at half maximum of the Bragg peak (nominally 5.5 mm) was found to be greater than 25 mm behind gas-soft-tissue interfaces. We address the implications of these data for dose computation with heavy charged particles.

SU-E-T-638: Evaluation and Comparison of Landauer Microstar (OSLD) Readers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souri, S; Ahmed, Y; Cao, Y

2014-06-15

Purpose: To evaluate and compare characteristic performance of a new Landauer nanodot Reader with the previous model. Methods: In order to calibrate and test the reader, a set of nanodots were irradiated using a Varian Truebeam Linac. Solid water slabs and bolus were used in the process of irradiation. Calibration sets of nanodots were irradiated for radiation dose ranges: 0 to 10 and 20 to 1000 cGy, using 6MV photons. Additionally, three sets of nanodots were each irradiated using 6MV, 10MV and 15MV beams. For each beam energy, and selected dose in the range of 3 to 1000 cGy, amore » pair of nanodots was irradiated and three readings were obtained with both readers. Results: The analysis shows that for 3 photon beam energies and selected ranges of dose, the calculated absorbed dose agrees well with the expected value. The results illustrate that the new Microstar II reader is a highly consistent system and that the repeated readings provide results with a reasonably small standard deviation. For all practical purposes, the response of system is linear for all radiation beam energies. Conclusion: The Microstar II nanodot reader is consistent, accurate, and reliable. The new hardware design and corresponding software contain several advantages over the previous model. The automatic repeat reading mechanism, that helps improve reproducibility and reduce processing time, and the smaller unit size that renders ease of transport, are two of such features. Present study shows that for high dose ranges a polynomial calibration equation provides more consistent results. A 3rd order polynomial calibration curve was used to analyze the readings of dosimeters exposed to high dose range radiation. It was observed that the results show less error compared to those calculated by using linear calibration curves, as provided by Landauer system software for all dose ranges.« less

High dose-per-pulse electron beam dosimetry: Usability and dose-rate independence of EBT3 Gafchromic films.

PubMed

Jaccard, Maud; Petersson, Kristoffer; Buchillier, Thierry; Germond, Jean-François; Durán, Maria Teresa; Vozenin, Marie-Catherine; Bourhis, Jean; Bochud, François O; Bailat, Claude

2017-02-01

The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose-per-pulse linear accelerator (linac), capable of delivering electron beams with a mean dose-rate (Ḋ m ) ranging from 0.07 to 3000 Gy/s and a dose-rate in pulse (Ḋ p ) of up to 8 × 10 6 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose-rate dependence of their response. Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋ m dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Ḋ m between 0.55 and 4.40 Gy/min, while Ḋ p dependence was probed at the prototype machine for Ḋ p ranging from 7 × 10 3 to 8 × 10 6 Gy/s. Ḋ p dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo-luminescent dosimeters (TLD) that have been reported as being dose-rate independent up to such high dose-rates. We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋ m dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋ p range attainable at the prototype linac confirming the absence of any dose-rate dependence within the investigated range (7 × 10 3 to 8 × 10 6 Gy/s). This aspect was further corroborated by the linear relationship between the dose-per-pulse (D p ) measured by films and the charge per pulse (C p ) measured at the prototype linac exit. Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose-rate and energy independent. © 2016 American Association of Physicists in Medicine.

The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.

PubMed Central

Baylor, D A; Nunn, B J; Schnapf, J L

1984-01-01

Visual transduction in rods of the cynomolgus monkey, Macaca fascicularis, was studied by recording membrane current from single outer segments projecting from small pieces of retina. Light flashes evoked transient outward-going photocurrents with saturating amplitudes of up to 34 pA. A flash causing twenty to fifty photoisomerizations gave a response of half the saturating amplitude. The response-stimulus relation was of the form 1-e-x where x is flash strength. The response to a dim flash usually had a time to peak of 150-250 ms and resembled the impulse response of a series of six low-pass filters. From the average spectral sensitivity of ten rods the rhodopsin was estimated to have a peak absorption near 491 nm. The spectral sensitivity of the rods was in good agreement with the average human scotopic visibility curve determined by Crawford (1949), when the human curve was corrected for lens absorption and self-screening of rhodopsin. Fluctuations in the photocurrent evoked by dim lights were consistent with a quantal event about 0.7 pA in peak amplitude. A steady light causing about 100 photoisomerizations s-1 reduced the flash sensitivity to half the dark-adapted value. At higher background levels the rod rapidly saturated. These results support the idea that dim background light desensitizes human scotopic vision by a mechanism central to the rod outer segments while scotopic saturation may occur within the outer segments. Recovery of the photocurrent after bright flashes was marked by quantized step-like events. The events had the properties expected if bleached rhodopsin in the disks occasionally caused an abrupt blockage of the dark current over about one-twentieth of the length of the outer segment. It is suggested that superposition of these events after bleaching may contribute to the threshold elevation measured psychophysically. The current in darkness showed random fluctuations which disappeared in bright light. The continuous component of the noise had a variance of about 0.03 pA2 and a power spectrum that fell to half near 3 Hz. A second component, consisting of discrete events resembling single-photon responses, was estimated to occur at a rate of 0.006 s-1. It is suggested that the continuous component of the noise may be removed from scotopic vision by a thresholding operation near the rod output. PMID:6512705

The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis.

PubMed

Baylor, D A; Nunn, B J; Schnapf, J L

1984-12-01

Visual transduction in rods of the cynomolgus monkey, Macaca fascicularis, was studied by recording membrane current from single outer segments projecting from small pieces of retina. Light flashes evoked transient outward-going photocurrents with saturating amplitudes of up to 34 pA. A flash causing twenty to fifty photoisomerizations gave a response of half the saturating amplitude. The response-stimulus relation was of the form 1-e-x where x is flash strength. The response to a dim flash usually had a time to peak of 150-250 ms and resembled the impulse response of a series of six low-pass filters. From the average spectral sensitivity of ten rods the rhodopsin was estimated to have a peak absorption near 491 nm. The spectral sensitivity of the rods was in good agreement with the average human scotopic visibility curve determined by Crawford (1949), when the human curve was corrected for lens absorption and self-screening of rhodopsin. Fluctuations in the photocurrent evoked by dim lights were consistent with a quantal event about 0.7 pA in peak amplitude. A steady light causing about 100 photoisomerizations s-1 reduced the flash sensitivity to half the dark-adapted value. At higher background levels the rod rapidly saturated. These results support the idea that dim background light desensitizes human scotopic vision by a mechanism central to the rod outer segments while scotopic saturation may occur within the outer segments. Recovery of the photocurrent after bright flashes was marked by quantized step-like events. The events had the properties expected if bleached rhodopsin in the disks occasionally caused an abrupt blockage of the dark current over about one-twentieth of the length of the outer segment. It is suggested that superposition of these events after bleaching may contribute to the threshold elevation measured psychophysically. The current in darkness showed random fluctuations which disappeared in bright light. The continuous component of the noise had a variance of about 0.03 pA2 and a power spectrum that fell to half near 3 Hz. A second component, consisting of discrete events resembling single-photon responses, was estimated to occur at a rate of 0.006 s-1. It is suggested that the continuous component of the noise may be removed from scotopic vision by a thresholding operation near the rod output.

Dosimetry in differentiated thyroid carcinoma (12-1402R)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier

2013-01-15

Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. Withmore » those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose-effect correlation could be determined.« less

Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women.

PubMed

McKeand, William

2017-09-01

Bazedoxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and lipid metabolism while having neutral or estrogen antagonist effects on the breast and endometrium. The present report describes findings from 3 Phase I clinical studies that evaluated the single-dose pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n = 23), and absolute bioavailability (study 3; n = 18) of bazedoxifene. All 3 studies enrolled healthy postmenopausal women who were either naturally postmenopausal or had undergone bilateral oophorectomy at least 6 months before the start of the study. Study 1 showed that unconjugated and total (unconjugated and conjugated) bazedoxifene levels increased proportionally with ascending oral doses of bazedoxifene (through the dose range of 5-120 mg). Evaluation with or without food intake was conducted at the 10-mg dose, with no clinically relevant effect on pharmacokinetic parameters. Study 2 showed that bazedoxifene achieved steady state in 1 week and exhibited linear pharmacokinetics in doses of 5 to 40 mg with no unexpected accumulation over the dose range. In accordance with a linear pharmacokinetic profile, mean maximum plasma concentration values increased with increasing dose, with values of 1.6, 6.2, and 12.5 ng/mL for the 5-, 20-, and 40-mg doses, respectively. In study 3, tablet and capsule formulations of bazedoxifene formulations had an estimated oral bioavailability of ~6%. The clearance of bazedoxifene was 0.4 (0.1) L/h/kg based on intravenous administration. The oral formulations had comparable exposure profiles with respect to AUC and AUC0-t, and the 90% CIs for these values were within the bioequivalence limits of 80% to 125%. Bazedoxifene was safe and well tolerated in all 3 studies. These pharmacokinetic evaluations in healthy postmenopausal women found that bazedoxifene displayed linear pharmacokinetics with doses ranging from 5 to 40 mg, with no unexpected accumulation. Food did not seem to have any clinically relevant impact on pharmacokinetic parameters. Bazedoxifene had an estimated oral bioavailability of ~6% and was safe and well tolerated in the range of doses evaluated. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

SU-F-T-613: Multi-Lesion Cranial SRS VMAT Plan Quality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ballangrud, A; Kuo, L; Happersett, L

Purpose: Cranial SRS VMAT plans must have steep dose gradient around each target to reduce dose to normal brain. This study reports on the correlation between gradient index (GI=V50%/V100%), target size and target dose heterogeneity index (HI=PTV Dmax/prescription dose) for multi-lesion cranial SRS VMAT plans. Methods: VMAT plans for 10 cranial cases with 3 to 6 lesions (total 39 lesions) generated in Varian Eclipse V11.0.47 with a fine-tuned AAA beam model and 0.125 cm dose grid were analyzed. One or two iso centers were used depending on the spatial distribution of lesions. Two to nine coplanar and non-coplanar arcs weremore » used per isocenter. Conformity index (CI= V100%/VPTV), HI, and GI were determined for each lesion. Dose to critical structures were recorded. Results: Lesion size ranged from 0.05–11.00 cm3. HI ranged from 1.2–1.4, CI ranged from 1.0–2.8 and GI from 3.1–8.4. Maximum dose to brainstem, chiasm, lenses, optic nerves and eyes ranged from 120–1946 cGy, 47–463 cGy, 9–121 cGy, 14–512 cGy, and 17–294 cGy, respectively. Brain minus PTV (Brain-PTV) V7Gy was in the range 1.1–6.5%, and Brain-PTV Dmean was in the range 94–324 cGy. Conclusion: This work shows that a GI < 5 can be achieved for lesions > 0.4cc. For smaller lesions, GI increases rapidly. GI is lower when HI is increased. Based on this study, recommend HI is 1.4, and recommended GI is for volumes <0.1cc GI<9, 0.1–0.4cc GI<6, 0.4–0.1.0cc GI<5, and for volumes >1.0cc GI<4. CI is < 1.3 for all lesions except for targets < 0.1cc. Cranial SRS VMAT plans must be optimized to lower the GI to reduce the dose to normal brain tissue.« less

Safety and immunogenicity of a primary series of Sabin-IPV with and without aluminum hydroxide in infants.

PubMed

Verdijk, Pauline; Rots, Nynke Y; van Oijen, Monique G C T; Weldon, William C; Oberste, M Steven; Okayasu, Hiromasa; Sutter, Roland W; Bakker, Wilfried A M

2014-09-03

An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle-income countries in the context of the global polio eradication initiative. Safety and immunogenicity of Sabin-IPV (sIPV) was evaluated in a double-blind, randomized, controlled, dose-escalation trial in the target population. Healthy infants (n=20/group) aged 56-63 days, received a primary series of three intramuscular injections with low-, middle- or high-dose sIPV with or without aluminum hydroxide or with the conventional IPV based on wild poliovirus strains (wIPV). Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after three vaccinations. The incidence of local and systemic reactions was comparable with the wIPV. Seroconversion rates after three vaccinations were 100% for type 2 and type 3 polioviruses (both Sabin and wild strains) and 95-100% for type 1 polioviruses. Median titers were high in all groups. Titers were well above the log2(titer) correlated with protection (=3) for all groups. Median titers for Sabin-2 were 9.3 (range 6.8-11.5) in the low-dose sIPV group, 9.2 (range 6.8-10.2) in the low-dose adjuvanted sIPV group and 9.8 (range 5.5-15.0) in the wIPV group, Median titers against MEF-1 (wild poliovirus type 2) were 8.2 (range 4.8-10.8) in the low-dose sIPV group, 7.3 (range 4.5-10.2) in the low-dose adjuvanted Sabin-IPV group and 10.3 (range 8.5-17.0) in the wIPV group. For all poliovirus types the median titers increased with increasing dose levels. sIPV and sIPV adjuvanted with aluminum hydroxide were immunogenic and safe at all dose levels, and comparable with the wIPV. EudraCTnr: 2011-003792-11, NCT01709071. Copyright © 2014. Published by Elsevier Ltd.

Genetic effects of radiotherapy for childhood cancer: gonadal dose reconstruction.

PubMed

Stovall, Marilyn; Donaldson, Sarah S; Weathers, Rita E; Robison, Leslie L; Mertens, Ann C; Winther, Jeanette Falck; Olsen, Jorgen H; Boice, John D

2004-10-01

To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death. The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account. Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy. Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.

Reversible anaesthesia of free-ranging lions (Panthera leo) in Zimbabwe.

PubMed

Fahlman, A; Loveridge, A; Wenham, C; Foggin, C; Arnemo, J M; Nyman, G

2005-12-01

The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo). Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg) were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg/kg (total dose 4-11 mg) and zolazepam-tiletamine at 0.38-1.32 mg/kg (total dose 50-275 mg) were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2) were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepam-tiletamine doses < 1 mg/kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.

Feasibility of MR-only proton dose calculations for prostate cancer radiotherapy using a commercial pseudo-CT generation method

NASA Astrophysics Data System (ADS)

Maspero, Matteo; van den Berg, Cornelis A. T.; Landry, Guillaume; Belka, Claus; Parodi, Katia; Seevinck, Peter R.; Raaymakers, Bas W.; Kurz, Christopher

2017-12-01

A magnetic resonance (MR)-only radiotherapy workflow can reduce cost, radiation exposure and uncertainties introduced by CT-MRI registration. A crucial prerequisite is generating the so called pseudo-CT (pCT) images for accurate dose calculation and planning. Many pCT generation methods have been proposed in the scope of photon radiotherapy. This work aims at verifying for the first time whether a commercially available photon-oriented pCT generation method can be employed for accurate intensity-modulated proton therapy (IMPT) dose calculation. A retrospective study was conducted on ten prostate cancer patients. For pCT generation from MR images, a commercial solution for creating bulk-assigned pCTs, called MR for Attenuation Correction (MRCAT), was employed. The assigned pseudo-Hounsfield Unit (HU) values were adapted to yield an increased agreement to the reference CT in terms of proton range. Internal air cavities were copied from the CT to minimise inter-scan differences. CT- and MRCAT-based dose calculations for opposing beam IMPT plans were compared by gamma analysis and evaluation of clinically relevant target and organ at risk dose volume histogram (DVH) parameters. The proton range in beam’s eye view (BEV) was compared using single field uniform dose (SFUD) plans. On average, a (2%, 2 mm) gamma pass rate of 98.4% was obtained using a 10% dose threshold after adaptation of the pseudo-HU values. Mean differences between CT- and MRCAT-based dose in the DVH parameters were below 1 Gy (<1.5% ). The median proton range difference was 0.1 mm, with on average 96% of all BEV dose profiles showing a range agreement better than 3 mm. Results suggest that accurate MR-based proton dose calculation using an automatic commercial bulk-assignment pCT generation method, originally designed for photon radiotherapy, is feasible following adaptation of the assigned pseudo-HU values.

There Is No Correlation Between Erectile Dysfunction and Dose to Penile Bulb and Neurovascular Bundles Following Real-Time Low-Dose-Rate Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solan, Amy N.; Cesaretti, Jamie A.; Stone, Nelson N.

2009-04-01

Purpose: We evaluated the relationship between the onset of erectile dysfunction and dose to the penile bulb and neurovascular bundles (NVBs) after real-time ultrasound-guided prostate brachytherapy. Methods and Materials: One hundred forty-seven patients who underwent prostate brachytherapy met the following eligibility criteria: (1) treatment with {sup 125}I brachytherapy to a prescribed dose of 160 Gy with or without hormones without supplemental external beam radiation therapy, (2) identification as potent before the time of implantation based on a score of 2 or higher on the physician-assigned Mount Sinai Erectile Function Score and a score of 16 or higher on the abbreviatedmore » International Index of Erectile Function patient assessment, and (3) minimum follow-up of 12 months. Median follow-up was 25.7 months (range, 12-47 months). Results: The 3-year actuarial rate of impotence was 23% (34 of 147 patients). An additional 43% of potent patients (49 of 113 patients) were using a potency aid at last follow-up. The penile bulb volume receiving 100% of the prescription dose (V{sub 100}) ranged from 0-0.05 cc (median, 0 cc), with a dose to the hottest 5% (D{sub 5}) range of 12.5-97.9 Gy (median, 40.8 Gy). There was no correlation between penile bulb D{sub 5} or V{sub 100} and postimplantation impotency on actuarial analysis. For the combined right and left NVB structures, V{sub 100} range was 0.3-5.1 cc (median, 1.8 cc), and V{sub 150} range was 0-1.5 cc (median, 0.31 cc). There was no association between NVB V{sub 100} or V{sub 150} and postimplantation impotency on actuarial analysis. Conclusion: Penile bulb doses are low after real-time ultrasound-guided prostate brachytherapy. We found no correlation between dose to either the penile bulb or NVBs and the development of postimplantation impotency.« less

Accounting for range uncertainties in the optimization of intensity modulated proton therapy.

PubMed

Unkelbach, Jan; Chan, Timothy C Y; Bortfeld, Thomas

2007-05-21

Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches--although conceptually different--yield very similar results on a qualitative level.

Treatment Plan Technique and Quality for Single-Isocenter Stereotactic Ablative Radiotherapy of Multiple Lung Lesions with Volumetric-Modulated Arc Therapy or Intensity-Modulated Radiosurgery

PubMed Central

Quan, Kimmen; Xu, Karen M.; Lalonde, Ron; Horne, Zachary D.; Bernard, Mark E.; McCoy, Chuck; Clump, David A.; Burton, Steven A.; Heron, Dwight E.

2015-01-01

The aim of this study is to provide a practical approach to the planning technique and evaluation of plan quality for the multi-lesion, single-isocenter stereotactic ablative radiotherapy (SABR) of the lung. Eleven patients with two or more lung lesions underwent single-isocenter volumetric-modulated arc therapy (VMAT) radiosurgery or IMRS. All plans were normalized to the target maximum dose. For each plan, all targets were treated to the same dose. Plan conformity and dose gradient were maximized with dose-control tuning structures surrounding targets. For comparison, multi-isocenter plans were retrospectively created for four patients. Conformity index (CI), homogeneity index (HI), gradient index (GI), and gradient distance (GD) were calculated for each plan. V5, V10, and V20 of the lung and organs at risk (OARs) were collected. Treatment time and total monitor units (MUs) were also recorded. One patient had four lesions and the remainder had two lesions. Six patients received VMAT and five patients received intensity-modulated radiosurgery (IMRS). For those treated with VMAT, two patients received 3-arc VMAT and four received 2-arc VMAT. For those treated with IMRS, two patients were treated with 10 and 11 beams, respectively, and the rest received 12 beams. Prescription doses ranged from 30 to 54 Gy in three to five fractions. The median prescribed isodose line was 84% (range: 80–86%). The median maximum dose was 57.1 Gy (range: 35.7–65.1 Gy). The mean combined PTV was 49.57 cm3 (range: 14.90–87.38 cm3). For single-isocenter plans, the median CI was 1.15 (range: 0.97–1.53). The median HI was 1.19 (range: 1.16–1.28). The median GI was 4.60 (range: 4.16–7.37). The median maximum radiation dose (Dmax) to total lung was 55.6 Gy (range: 35.7–62.0 Gy). The median mean radiation dose to the lung (Dmean) was 4.2 Gy (range: 1.1–9.3 Gy). The median lung V5 was 18.7% (range: 3.8–41.3%). There was no significant difference in CI, HI, GI, GD, V5, V10, and V20 (lung, heart, trachea, esophagus, and spinal cord) between single-isocenter and multi-isocenter plans. This multi-lesion, single-isocenter lung SABR planning technique demonstrated excellent plan quality and clinical efficiency and is recommended for radiosurgical treatment of two or more lung targets for well-suited patients. PMID:26500888

Assessment of radiation doses from residential smoke detectors that contain americium-241

NASA Astrophysics Data System (ADS)

Odonnell, F. R.; Etnier, E. L.; Holton, G. A.; Travis, C. C.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv to 20 nSv for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 micro-Sv (0.0006 to 8 mrem) to total body and from 0.06 to 800 micro-Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft squared.

TU-H-CAMPUS-JeP1-05: Dose Deformation Error Associated with Deformable Image Registration Pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Surucu, M; Woerner, A; Roeske, J

Purpose: To evaluate errors associated with using different deformable image registration (DIR) pathways to deform dose from planning CT (pCT) to cone-beam CT (CBCT). Methods: Deforming dose is controversial because of the lack of quality assurance tools. We previously proposed a novel metric to evaluate dose deformation error (DDE) by warping dose information using two methods, via dose and contour deformation. First, isodose lines of the pCT were converted into structures and then deformed to the CBCT using an image based deformation map (dose/structure/deform). Alternatively, the dose matrix from the pCT was deformed to CBCT using the same deformation map,more » and then the same isodose lines of the deformed dose were converted into structures (dose/deform/structure). The doses corresponding to each structure were queried from the deformed dose and full-width-half-maximums were used to evaluate the dose dispersion. The difference between the FWHM of each isodose level structure is defined as the DDE. Three head-and-neck cancer patients were identified. For each patient, two DIRs were performed between the pCT and CBCT, either deforming pCT-to-CBCT or CBCT-to-pCT. We evaluated the errors associated by using either of these pathways to deform dose. A commercially available, Demons based DIR was used for this study, and 10 isodose levels (20% to 105%) were used to evaluate the errors in various dose levels. Results: The prescription dose for all patients was 70 Gy. The mean DDE for CT-to-CBCT deformation was 1.0 Gy (range: 0.3–2.0 Gy) and this was increased to 4.3 Gy (range: 1.5–6.4 Gy) for CBCT-to-CT deformation. The mean increase in DDE between the two deformations was 3.3 Gy (range: 1.0–5.4 Gy). Conclusion: The proposed DDF was used to quantitatively estimate dose deformation errors caused by different pathways to perform DIR. Deforming dose using CBCT-to-CT deformation produced greater error than CT-to-CBCT deformation.« less

Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation.

PubMed

Tran, Van; Little, Mark P

2017-11-01

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and non-malignant, show downward curvature in the dose response, and for most endpoints this is statistically significant (p < 0.05). Associated with this, the low-dose extrapolation factor associated with neutron exposure is generally statistically significantly less than 1 for most malignant and non-malignant endpoints, with central estimates mostly in the range 0.1-0.9. In contrast to the situation at higher dose rates, there are statistically non-significant decreases of risk per unit dose at gamma dose rates of less than or equal to 5 mGy/h for most malignant endpoints, and generally non-significant increases in risk per unit dose at gamma dose rates ≤5 mGy/h for most non-malignant endpoints. Associated with this, the dose-rate extrapolation factor, the ratio of high dose-rate to low dose-rate (≤5 mGy/h) gamma dose response slopes, for many tumour sites is in the range 1.2-2.3, albeit not statistically significantly elevated from 1, while for most non-malignant endpoints the gamma dose-rate extrapolation factor is less than 1, with most estimates in the range 0.2-0.8. After neutron exposure there are non-significant indications of lower risk per unit dose at dose rates ≤5 mGy/h compared to higher dose rates for most malignant endpoints, and for all tumours (p = 0.001), and respiratory tumours (p = 0.007) this reduction is conventionally statistically significant; for most non-malignant outcomes risks per unit dose non-significantly increase at lower dose rates. Associated with this, the neutron dose-rate extrapolation factor is less than 1 for most malignant and non-malignant endpoints, in many cases statistically significantly so, with central estimates mostly in the range 0.0-0.2.

Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter.

PubMed

Venning, A J; Mather, M L; Baldock, C

2005-06-01

The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and R2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the R2-dose response and R2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest R2-dose response and R2-dose sensitivity occurred at 96 hours.

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer.

PubMed

Wu, Chen-Ta; Motegi, Atsushi; Motegi, Kana; Hotta, Kenji; Kohno, Ryosuke; Tachibana, Hidenobu; Kumagai, Motoki; Nakamura, Naoki; Hojo, Hidehiro; Niho, Seiji; Goto, Koichi; Akimoto, Tetsuo

2016-08-10

To assess the feasibility of proton beam therapy for the patients with locally advanced non-small lung cancer. The dosimetry was analyzed retrospectively to calculate the doses to organs at risk, such as the lung, heart, esophagus and spinal cord. A dosimetric comparison between proton beam therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy) plans was performed. Dummy intensity-modulated radiotherapy plans were also generated for the patients for whom curative three-dimensional conformal radiotherapy plans could not be generated. Overall, 33 patients with stage III non-small cell lung cancer were treated with proton beam therapy between December 2011 and August 2014. The median age of the eligible patients was 67 years (range: 44-87 years). All the patients were treated with chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was 23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0-19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal radiotherapy planning, 12 patients were regarded as not being suitable for radical thoracic three-dimensional conformal radiotherapy. All the dose parameters of proton beam therapy, except for the esophageal dose, were lower than those for the dummy three-dimensional conformal radiotherapy plans. In comparison to the intensity-modulated radiotherapy plan, proton beam therapy also achieved dose reduction in the normal lung. None of the patients experienced grade 4 or worse non-hematological toxicities. Proton beam therapy for patients with stage III non-small cell lung cancer was feasible and was superior to three-dimensional conformal radiotherapy for several dosimetric parameters. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SU-F-T-184: 3D Range-Modulator for Scanned Particle Therapy: Development, Monte Carlo Simulations and Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simeonov, Y; Penchev, P; Ringbaek, T Printz

2016-06-15

Purpose: Active raster scanning in particle therapy results in highly conformal dose distributions. Treatment time, however, is relatively high due to the large number of different iso-energy layers used. By using only one energy and the so called 3D range-modulator irradiation times of a few seconds only can be achieved, thus making delivery of homogeneous dose to moving targets (e.g. lung cancer) more reliable. Methods: A 3D range-modulator consisting of many pins with base area of 2.25 mm2 and different lengths was developed and manufactured with rapid prototyping technique. The form of the 3D range-modulator was optimised for a sphericalmore » target volume with 5 cm diameter placed at 25 cm in a water phantom. Monte Carlo simulations using the FLUKA package were carried out to evaluate the modulating effect of the 3D range-modulator and simulate the resulting dose distribution. The fine and complicated contour form of the 3D range-modulator was taken into account by a specially programmed user routine. Additionally FLUKA was extended with the capability of intensity modulated scanning. To verify the simulation results dose measurements were carried out at the Heidelberg Ion Therapy Center (HIT) with a 400.41 MeV 12C beam. Results: The high resolution measurements show that the 3D range-modulator is capable of producing homogeneous 3D conformal dose distributions, simultaneously reducing significantly irradiation time. Measured dose is in very good agreement with the previously conducted FLUKA simulations, where slight differences were traced back to minor manufacturing deviations from the perfect optimised form. Conclusion: Combined with the advantages of very short treatment time the 3D range-modulator could be an alternative to treat small to medium sized tumours (e.g. lung metastasis) with the same conformity as full raster-scanning treatment. Further simulations and measurements of more complex cases will be conducted to investigate the full potential of the 3D range-modulator.« less

Validation of a low dose simulation technique for computed tomography images.

PubMed

Muenzel, Daniela; Koehler, Thomas; Brown, Kevin; Zabić, Stanislav; Fingerle, Alexander A; Waldt, Simone; Bendik, Edgar; Zahel, Tina; Schneider, Armin; Dobritz, Martin; Rummeny, Ernst J; Noël, Peter B

2014-01-01

Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT) images from an original higher dose scan. Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV) of a swine were acquired (approved by the regional governmental commission for animal protection). Simulations of CT acquisition with a lower dose (simulated 10-80 mAs) were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was -1.2% (range -9% to 3.2%) and -0.2% (range -8.2% to 3.2%), respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9-10.2 HU (noise) and 1.9-13.4 HU (CT values), without significant differences (p>0.05). Subjective observer evaluation of image appearance showed no visually detectable difference. Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques.

Computational analysis of the dose rates at JSI TRIGA reactor irradiation facilities.

PubMed

Ambrožič, K; Žerovnik, G; Snoj, L

2017-12-01

The JSI TRIGA Mark II, IJS research reactor is equipped with numerous irradiation positions, where samples can be irradiated by neutrons and γ-rays. Irradiation position selection is based on its properties, such as physical size and accessibility, as well as neutron and γ-ray spectra, flux and dose intensities. This paper presents an overview on the neutron and γ-ray fluxes, spectra and dose intensities calculations using Monte Carlo MCNP software and ENDF/B-VII.0 nuclear data libraries. The dose-rates are presented in terms of ambient dose equivalents, air kerma, and silicon dose equivalent. At full reactor power the neutron ambient dose equivalent ranges from 5.5×10 3 Svh -1 to 6×10 6 Svh -1 , silicon dose equivalent from 6×10 2 Gy/h si to 3×10 5 Gy/h si , and neutron air kerma from 4.3×10 3 Gyh -1 to 2×10 5 Gyh -1 . Ratio of fast (1MeV

High-pitch computed tomography coronary angiography-a new dose-saving algorithm: estimation of radiation exposure.

PubMed

Ketelsen, Dominik; Buchgeister, Markus; Korn, Andreas; Fenchel, Michael; Schmidt, Bernhard; Flohr, Thomas G; Thomas, Christoph; Schabel, Christoph; Tsiflikas, Ilias; Syha, Roland; Claussen, Claus D; Heuschmid, Martin

2012-01-01

Purpose. To estimate effective dose and organ equivalent doses of prospective ECG-triggered high-pitch CTCA. Materials and Methods. For dose measurements, an Alderson-Rando phantom equipped with thermoluminescent dosimeters was used. The effective dose was calculated according to ICRP 103. Exposure was performed on a second-generation dual-source scanner (SOMATOM Definition Flash, Siemens Medical Solutions, Germany). The following scan parameters were used: 320 mAs per rotation, 100 and 120 kV, pitch 3.4 for prospectively ECG-triggered high-pitch CTCA, scan range of 13.5 cm, collimation 64 × 2 × 0.6 mm with z-flying focal spot, gantry rotation time 280 ms, and simulated heart rate of 60 beats per minute. Results. Depending on the applied tube potential, the effective whole-body dose of the cardiac scan ranged from 1.1 mSv to 1.6 mSv and from 1.2 to 1.8 mSv for males and females, respectively. The radiosensitive breast tissue in the range of the primary beam caused an increased female-specific effective dose of 8.6%±0.3% compared to males. Decreasing the tube potential, a significant reduction of the effective dose of 35.8% and 36.0% can be achieved for males and females, respectively (P < 0.001). Conclusion. The radiologist and the CT technician should be aware of this new dose-saving strategy to keep the radiation exposure as low as reasonablly achievable.

32 CFR 218.3 - Dose reconstruction methodology.

Code of Federal Regulations, 2013 CFR

2013-07-01

... effects of shot-specific parameters such as weapon type and yield, neutron and gamma output, source and... specific personnel activities. Due to the range of activities, times, geometries, shielding, and weapon... that could have led to atypical doses. Radiation dose from neutrons and dose commitments due to inhaled...

32 CFR 218.3 - Dose reconstruction methodology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... effects of shot-specific parameters such as weapon type and yield, neutron and gamma output, source and... specific personnel activities. Due to the range of activities, times, geometries, shielding, and weapon... that could have led to atypical doses. Radiation dose from neutrons and dose commitments due to inhaled...

32 CFR 218.3 - Dose reconstruction methodology.

Code of Federal Regulations, 2012 CFR

2012-07-01

... effects of shot-specific parameters such as weapon type and yield, neutron and gamma output, source and... specific personnel activities. Due to the range of activities, times, geometries, shielding, and weapon... that could have led to atypical doses. Radiation dose from neutrons and dose commitments due to inhaled...

Neutron organ dose and the influence of adipose tissue

NASA Astrophysics Data System (ADS)

Simpkins, Robert Wayne

Neutron fluence to dose conversion coefficients have been assessed considering the influences of human adipose tissue. Monte Carlo code MCNP4C was used to simulate broad parallel beam monoenergetic neutrons ranging in energy from thermal to 10 MeV. Simulated Irradiations were conducted for standard irradiation geometries. The targets were on gender specific mathematical anthropomorphic phantoms modified to approximate human adipose tissue distributions. Dosimetric analysis compared adipose tissue influence against reference anthropomorphic phantom characteristics. Adipose Male and Post-Menopausal Female Phantoms were derived introducing interstitial adipose tissue to account for 22 and 27 kg additional body mass, respectively, each demonstrating a Body Mass Index (BMI) of 30. An Adipose Female Phantom was derived introducing specific subcutaneous adipose tissue accounting for 15 kg of additional body mass demonstrating a BMI of 26. Neutron dose was shielded in the superficial tissues; giving rise to secondary photons which dominated the effective dose for Incident energies less than 100 keV. Adipose tissue impact on the effective dose was a 25% reduction at the anterior-posterior incidence ranging to a 10% increase at the lateral incidences. Organ dose impacts were more distinctive; symmetrically situated organs demonstrated a 15% reduction at the anterior-posterior Incidence ranging to a 2% increase at the lateral incidences. Abdominal or asymmetrically situated organs demonstrated a 50% reduction at the anterior-posterior incidence ranging to a 25% increase at the lateral incidences.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giantsoudi, D; Adams, J; MacDonald, S

Purpose: In proton radiation therapy of posterior fossa tumors, to spare other sensitive structures, the preferred beam geometry results in placing the treatment field distal edge within or just beyond the brainstem, including in at least partially in the treatment volume. Concerns for brainstem toxicity are increased and a controversy exists as to weather the beam’s distal edge should be placed within the brainstem or beyond it, to avoid elevated linear energy transfer (LET) and relative biological effectiveness (RBE) within the brainstem. The dosimetric efficacy of these techniques was examined, accounting for LET- and dose-dependent variable RBE distributions. Methods: Threemore » treatment planning techniques were applied in six ependymoma cases: (a) three-field dose-sparing, with beams’ distal edge within the brainstem; (b) three-field LET-sparing, using same beam directions as (a) but extended field ranges beyond the brainstem; (c) two-posterior-oblique LET-sparing, with extended ranges as (b). Monte Carlo calculated dose, LET and RBE-weighted dose distributions were compared. Results: Lower LET values in the brainstem were accompanied by higher median dose: 53.7 Gy[RBE] and 54.3 Gy[RBE] for techniques (b) and (c) versus 52.1 Gy[RBE] for (a). Accounting for variable RBE, a 15% increase of the brainstem volume receiving at least 60 Gy[RBE] was observed for technique (c) versus (a). Maximum variable-RBE-weighted brainstem dose was comparable for all techniques. Conclusion: Extending the treatment beam range beyond the brainstem, significantly increased its volume receiving high dose radiation, even when accounting for the decreased LET values. The dosimetric benefits of techniques limiting the brainstem dose may outweigh the impact of LET reduction achieved through this technique, especially since clinical consequences of increased LET at the end of range have not been proven yet.« less

Childhood leukemia incidence and exposure to indoor radon, terrestrial and cosmic gamma radiation.

PubMed

Evrard, Anne-Sophie; Hémon, Denis; Billon, Solenne; Laurier, Dominique; Jougla, Eric; Tirmarche, Margot; Clavel, Jacqueline

2006-06-01

This study was undertaken to evaluate the ecological association between terrestrial and cosmic gamma radiation, indoor radon, and acute leukemia incidence among children under 15 y of age. From 1990 to 2001, 5,330 cases of acute leukemia were registered by the French National Registry of Childhood Leukemia and Lymphoma. Exposure to terrestrial gamma radiation was based on measurements, using thermoluminescent dosimeters, at about 1,000 sites covering all the "Départements." In addition, 8,737 indoor terrestrial gamma dose rate measurements covering 62% of the "Départements" and 13,240 indoor radon concentration measurements covering all the "Départements" were made during a national campaign. Cosmic ray doses were estimated in each of the 36,363 "Communes" of France. There was no evidence of an ecological association between terrestrial gamma dose (range: 0.22-0.90 mSv y) or total gamma dose (range: 0.49-1.28 mSv y) and childhood acute leukemia incidence, for acute myeloid leukemia (AML) or for acute lymphoblastic leukemia (ALL), in univariate or multivariate regression analyses including indoor radon. A significant positive association between indoor radon (range: 22-262 Bq m) and AML incidence among children was observed and remained significant in multivariate regression analyses including either terrestrial gamma dose [SIR per 100 Bq m = 1.29 (1.09-1.53)] or total gamma dose [SIR per 100 Bq m = 1.29 (1.09-1.53)]. The study showed no ecological association between terrestrial gamma radiation and childhood leukemia for the range of variation in gamma dose rates observed in France. The moderate ecological association between childhood AML incidence and indoor radon does not appear to be confounded by terrestrial gamma dose.

Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants.

PubMed

Tekgündüz, Kadir Şerafettin; Ceviz, Naci; Caner, İbrahim; Olgun, Haşim; Demirelli, Yaşar; Yolcu, Canan; Şahin, İrfan Oğuz; Kara, Mustafa

2015-08-01

Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology.

PubMed

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C; Morelli, John N

2017-01-01

We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms "interventional/computed tomography" and "radiation dose/radiation dose reduction." A PubMed query using the above-mentioned search terms for the years of 2005-2015 was performed. Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6-27) and 246±105 diagnostic radiology abstracts (range, 112-389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79-187) and 1205±307 publications (range, 829-1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted.

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology

PubMed Central

Hansmann, Jan; Henzler, Thomas; Gaba, Ron C.; Morelli, John N.

2017-01-01

PURPOSE We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities. METHODS Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms “interventional/computed tomography” and “radiation dose/radiation dose reduction.” A PubMed query using the above-mentioned search terms for the years of 2005–2015 was performed. RESULTS Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6–27) and 246±105 diagnostic radiology abstracts (range, 112–389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79–187) and 1205±307 publications (range, 829–1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001). CONCLUSION The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted. PMID:28287072

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Direct Measurement of Perchlorate Exposure Biomarkers in a Highly Exposed Population: A Pilot Study

PubMed Central

Wong, Michelle; Copan, Lori; Olmedo, Luis; Patton, Sharyle; Haas, Robert; Atencio, Ryan; Xu, Juhua; Valentin-Blasini, Liza

2011-01-01

Exposure to perchlorate is ubiquitous in the United States and has been found to be widespread in food and drinking water. People living in the lower Colorado River region may have perchlorate exposure because of perchlorate in ground water and locally-grown produce. Relatively high doses of perchlorate can inhibit iodine uptake and impair thyroid function, and thus could impair neurological development in utero. We examined human exposures to perchlorate in the Imperial Valley among individuals consuming locally grown produce and compared perchlorate exposure doses to state and federal reference doses. We collected 24-hour urine specimen from a convenience sample of 31 individuals and measured urinary excretion rates of perchlorate, thiocyanate, nitrate, and iodide. In addition, drinking water and local produce were also sampled for perchlorate. All but two of the water samples tested negative for perchlorate. Perchlorate levels in 79 produce samples ranged from non-detect to 1816 ppb. Estimated perchlorate doses ranged from 0.02 to 0.51 µg/kg of body weight/day. Perchlorate dose increased with the number of servings of dairy products consumed and with estimated perchlorate levels in produce consumed. The geometric mean perchlorate dose was 70% higher than for the NHANES reference population. Our sample of 31 Imperial Valley residents had higher perchlorate dose levels compared with national reference ranges. Although none of our exposure estimates exceeded the U. S. EPA reference dose, three participants exceeded the acceptable daily dose as defined by bench mark dose methods used by the California Office of Environmental Health Hazard Assessment. PMID:21394205

Performance characteristics of the EPR dosimetry system with table sugar in radiotherapy applications.

PubMed

Mikou, M; Ghosne, N; El Baydaoui, R; Zirari, Z; Kuntz, F

2015-05-01

Performance characteristics of the megavoltage photon dose measurements with EPR and table sugar were analyzed. An advantage of sugar as a dosimetric material is its tissue equivalency. The minimal detectable dose was found to be 1.5Gy for both the 6 and 18MV photons. The dose response curves are linear up to at least 20Gy. The energy dependence of the dose response in the megavoltage energy range is very weak and probably statistically insignificant. Reproducibility of measurements of various doses in this range performed with the peak-to-peak and double-integral methods is reported. The method can be used in real-time dosimetry in radiation therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

PubMed

Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses.

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

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

BENZENE METABOLISM IN RODENTS AT DOSES RELEVANT TO HUMAN EXPOSURE FROM URBAN AIR

EPA Science Inventory

Investigators, led by Dr. Kenneth Turteltaub, researched benzene metabolism in rodents over a hundred million–fold dose range. This range encompassed concentrations close to those of human ambient exposure, generally 1 to 10 parts per billion. Turteltaub and his ...

SU-G-TeP4-04: An Automated Monte Carlo Based QA Framework for Pencil Beam Scanning Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, J; Jee, K; Clasie, B

2016-06-15

Purpose: Prior to treating new PBS field, multiple (three) patient-field-specific QA measurements are performed: two 2D dose distributions at shallow depth (M1) and at the tumor depth (M2) with treatment hardware at zero gantry angle; one 2D dose distribution at iso-center (M3) without patient specific devices at the planned gantry angle. This patient-specific QA could be simplified by the use of MC model. The results of MC model commissioning for a spot-scanning system and the fully automated TOPAS/MC-based QA framework will be presented. Methods: We have developed in-house MC interface to access a TPS (Astroid) database from a computer clustermore » remotely. Once a plan is identified, the interface downloads information for the MC simulations, such as patient images, apertures points, and fluence maps and initiates calculations in both the patient and QA geometries. The resulting calculations are further analyzed to evaluate the TPS dose accuracy and the PBS delivery. Results: The Monte Carlo model of our system was validated within 2.0 % accuracy over the whole range of the dose distribution (proximal/shallow part, as well as target dose part) due to the location of the measurements. The averaged range difference after commissioning was 0.25 mm over entire treatment ranges, e.g., 6.5 cm to 31.6 cm. Conclusion: As M1 depths range typically from 1 cm to 4 cm from the phantom surface, The Monte Carlo model of our system was validated within +− 2.0 % in absolute dose level over a whole treatment range. The averaged range difference after commissioning was 0.25 mm over entire treatment ranges, e.g., 6.5 cm to 31.6 cm. This work was supported by NIH/NCI under CA U19 21239.« less

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.

Oseltamivir Pharmacokinetics, Dosing, and Resistance Among Children Aged <2 Years With Influenza

PubMed Central

Kimberlin, David W.; Acosta, Edward P.; Prichard, Mark N.; Sánchez, Pablo J.; Ampofo, Krow; Lang, David; Ashouri, Negar; Vanchiere, John A.; Abzug, Mark J.; Abughali, Nazha; Caserta, Mary T.; Englund, Janet A.; Sood, Sunil K.; Spigarelli, Michael G.; Bradley, John S.; Lew, Judy; Michaels, Marian G.; Wan, Wen; Cloud, Gretchen; Jester, Penelope; Lakeman, Fred D.; Whitley, Richard J.; Giles, Dusty; Cotton, Bari; Judy, Sharon; Cowie, Margaret; Francis, Jeanne; Evans, Candice; O'Donnell, Nan; Shiraishi, Ofelia Vargas; Latiolais, Lisa; Aymami, Valeri; Dole, Ken; Gaultier, Julie; Lofthus, Gerry; Kinnunen, Diane; Lacombe, Kirsten; Stellato, Nancy; Denlinger, Julie; Hingtgen, Sara; Mason, Christina; Jeffrey, Noreen

2013-01-01

Background. Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown. Methods. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age–de-escalation, adaptive design with a targeted systemic exposure. Results. From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0–8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9–11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12–23 months receiving the Food and Drug Administration–approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment. Conclusions. The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9–11 months old is 3.5 mg/kg. Clinical Trials Registration. NCT00391768. PMID:23230059

Patient-specific dose estimation for pediatric abdomen-pelvis CT

NASA Astrophysics Data System (ADS)

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

2009-02-01

The purpose of this study is to develop a method for estimating patient-specific dose from abdomen-pelvis CT examinations and to investigate dose variation across patients in the same weight group. Our study consisted of seven pediatric patients in the same weight/protocol group, for whom full-body computer models were previously created based on the patients' CT data obtained for clinical indications. Organ and effective dose of these patients from an abdomen-pelvis scan protocol (LightSpeed VCT scanner, 120-kVp, 85-90 mA, 0.4-s gantry rotation period, 1.375-pitch, 40-mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated for the same CT system. The seven patients had effective dose of 2.4-2.8 mSv, corresponding to normalized effective dose of 6.6-8.3 mSv/100mAs (coefficient of variation: 7.6%). Dose variations across the patients were small for large organs in the scan coverage (mean: 6.6%; range: 4.9%-9.2%), larger for small organs in the scan coverage (mean: 10.3%; range: 1.4%-15.6%), and the largest for organs partially or completely outside the scan coverage (mean: 14.8%; range: 5.7%-27.7%). Normalized effective dose correlated strongly with body weight (correlation coefficient: r = -0.94). Normalized dose to the kidney and the adrenal gland correlated strongly with mid-liver equivalent diameter (kidney: r = -0.97; adrenal glands: r = -0.98). Normalized dose to the small intestine correlated strongly with mid-intestine equivalent diameter (r = -0.97). These strong correlations suggest that patient-specific dose may be estimated for any other child in the same size group who undergoes the abdomen-pelvis scan.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, J.J.; Friedman, R.; Orr, K.

1990-05-01

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

Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

PubMed Central

Ron, Elaine; Brenner, Alina

2013-01-01

Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karlsson, Kristin, E-mail: kristin.karlsson@karolinska.se; Department of Oncology-Pathology, Karolinska Institute, Stockholm; Nyman, Jan

2013-11-01

Purpose: To evaluate the dose–response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm{sup 3} up to 2.0 cm{sup 3}]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showedmore » a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm{sup 3} (D{sub 0.1cm3}) was used for further analysis. The median value of D{sub 0.1cm3} (α/β = 3 Gy) was EQD{sub 2,LQ} = 147 Gy{sub 3} (range, 20-293 Gy{sub 3}). For patients who developed atelectasis the median value was EQD{sub 2,LQ} = 210 Gy{sub 3}, and for patients who did not develop atelectasis, EQD{sub 2,LQ} = 105 Gy{sub 3}. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose–response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.« less

SU-E-J-08: Comparison of Unintended Radiation Doses to Organs at Risk Resulting From the Out-Of-Field Therapeutic Beams and From Image-Guidance X-Ray Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, G; Wang, L

Purpose: The unintended radiation dose to organs at risk (OAR) can be contributed from imaging guidance procedures as well as from leakage and scatter of therapeutic beams. This study compares the imaging dose with the unintended out-of-field therapeutic dose to patient sensitive organs. Methods: The Monte Carlo EGSnrc user codes, BEAMnrc and DOSXYZnrc, were used to simulate kV X-ray sources from imaging devices as well as the therapeutic IMRT/VMAT beams and to calculate doses to target and OARs on patient treatment planning CT images. The accuracy of the Monte Carlo simulations was benchmarked against measurements in phantoms. The dose-volume histogrammore » was utilized in analyzing the patient organ doses. Results: The dose resulting from Standard Head kV-CBCT scans to bone and soft tissues ranges from 0.7 to 1.1 cGy and from 0.03 to 0.3 cGy, respectively. The dose resulting from Thorax scans on the chest to bone and soft tissues ranges from 1.1 to 1.8 cGy and from 0.3 to 0.6 cGy, respectively. The dose resulting from Pelvis scans on the abdomen to bone and soft tissues range from 3.2 to 4.2 cGy and from 1.2 to 2.2 cGy, respectively. The out-of-field doses to OAR are sensitive to the distance between the treated target and the OAR. For a typical Head-and-Neck IMRT/VMAT treatment the out-of-field doses to eyes are 1–3% of the target dose, or 2–6 cGy per fraction. Conclusion: The imaging doses to OAR are predictable based on the imaging protocols used when OARs are within the imaged volume and can be estimated and accounted for by using tabulated values. The unintended out-of-field doses are proportional to the target dose, strongly depend on the distance between the treated target and OAR, and are generally higher comparing to the imaging dose. This work was partially supported by Varian research grant VUMC40590.« less

Lack of Radiation Maculopathy After Palladium-103 Plaque Radiotherapy for Iris Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yousef, Yacoub A.; Finger, Paul T., E-mail: pfinger@eyecancer.com

2012-07-15

Purpose: To report on the risk of radiation maculopathy for iris and iridociliary melanomas treated by {sup 103}Pd plaque radiotherapy. Methods and Materials: This is a retrospective clinical case series of 30 eyes in 30 patients with melanomas limited to the iris or invading the ciliary body. The main outcome measures included demographic information, laterality, tumor size, location, visual acuity, radiation dose, local control, retinal evaluation, and duration of follow-up. Results: Thirty patients were followed for a median 36 months (range, 12-90 months). Sixteen of 30 tumors (53%) were pure iris melanomas, and 14 (47%) were primary iris melanomas extendingmore » into the ciliary body. Radiation dosimetry showed that the median tumor apex dose was 85 Gy (range, 75-100 Gy), lens dose 43.5 Gy (range, 17.8-60 Gy), fovea dose 1.8 Gy (range, 1.3-5 Gy), and central optic disc dose 1.7 Gy (range, 1.3-4.7 Gy). Cataracts developed in 20 of the 28 phakic eyes (71.4%). No patient in this series developed radiation maculopathy or radiation optic neuropathy. Last best-corrected visual acuity was {>=}20/25 in 28 patients (93%) at a median 36 months' follow-up. Conclusion: Though visual acuities were transiently affected by radiation cataract, no radiation maculopathy or optic neuropathy has been noted after {sup 103}Pd treatment of iris and iridociliary melanomas.« less

Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

PubMed

Inaniwa, Taku; Kohno, Toshiyuki; Tomitani, Takehiro; Urakabe, Eriko; Sato, Shinji; Kanazawa, Mitsutaka; Kanai, Tatsuaki

2006-09-07

In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an ionization chamber. The good agreement between the derived and the measured distributions implies that the deposited dose distribution in a target can be estimated from the detected annihilation gamma-ray distribution with a positron camera.

Dose Response Data for Hormonally Active Chemicals: Estrogens, Antiandrogens and Androgens

EPA Science Inventory

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

First clinical implementation of the Capri applicator

PubMed Central

2014-01-01

This study was to assess the Capri applicator for patients with endometrial cancer undergoing high‐radiation dose treatments following external‐beam radiation therapy. The Capri applicator is an inflatable vaginal cylinder with multiple channels. It is used to tailor the dose distribution to an asymmetric vaginal disease, and better spare organs at risk. Five patients with high‐risk endometrial cancer were selected for this study. The patients were treated with a high dose of radiation using the Capri applicator: daily fraction of 7 Gy was prescribed for a total dose of 21 Gy. The treatment plans included radiobiological parameters such as equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and tumor control probability (TCP). Based on the dose‐volume histograms (DVH), we also calculated four quality factors: conformity index (CI), dose homogeneity index (DHI), dose nonuniformity index (DNR), and overdose index (OI). The TCP values range from 82.26% to 95.92%. Very low values of NTCP were observed for the bladder and rectum. The EUDs to organs at risk ranged from 4.65 Gy to 18.22 Gy for the bladder, and from 3.41 Gy from to 6.56 Gy for the rectum. The mean CI was 1.05(SD=0.0008). The mean DNR was 0.10(range0.0−0.295,SD=0.100). The mean OI was 0.019(SD=0.028). The DHIs were in the range of 1.0−0.754(mean0.886,SD=0.116). The use of a multichannel vaginal cylinder may not only help cover extensive vaginal disease, but also reduce the dose to the rectum. This dosimetric analysis shows that rectal doses could be reduced using a multichannel cylinder. However, the dose delivered to the bladder based on EUD calculation may be higher than that obtained with other methods. Each patient must be evaluated independently to determine if a multichannel treatment is appropriate. Clinical followup will show whether this rectal dose sparing translates into a real toxicity improvement. PACS number: 3.6.96.0 PMID:24423857

Independent dose verification system with Monte Carlo simulations using TOPAS for passive scattering proton therapy at the National Cancer Center in Korea

NASA Astrophysics Data System (ADS)

Shin, Wook-Geun; Testa, Mauro; Kim, Hak Soo; Jeong, Jong Hwi; Byeong Lee, Se; Kim, Yeon-Joo; Min, Chul Hee

2017-10-01

For the independent validation of treatment plans, we developed a fully automated Monte Carlo (MC)-based patient dose calculation system with the tool for particle simulation (TOPAS) and proton therapy machine installed at the National Cancer Center in Korea to enable routine and automatic dose recalculation for each patient. The proton beam nozzle was modeled with TOPAS to simulate the therapeutic beam, and MC commissioning was performed by comparing percent depth dose with the measurement. The beam set-up based on the prescribed beam range and modulation width was automated by modifying the vendor-specific method. The CT phantom was modeled based on the DICOM CT files with TOPAS-built-in function, and an in-house-developed C++ code directly imports the CT files for positioning the CT phantom, RT-plan file for simulating the treatment plan, and RT-structure file for applying the Hounsfield unit (HU) assignment, respectively. The developed system was validated by comparing the dose distributions with those calculated by the treatment planning system (TPS) for a lung phantom and two patient cases of abdomen and internal mammary node. The results of the beam commissioning were in good agreement of up to 0.8 mm2 g-1 for B8 option in both of the beam range and the modulation width of the spread-out Bragg peaks. The beam set-up technique can predict the range and modulation width with an accuracy of 0.06% and 0.51%, respectively, with respect to the prescribed range and modulation in arbitrary points of B5 option (128.3, 132.0, and 141.2 mm2 g-1 of range). The dose distributions showed higher than 99% passing rate for the 3D gamma index (3 mm distance to agreement and 3% dose difference) between the MC simulations and the clinical TPS in the target volume. However, in the normal tissues, less favorable agreements were obtained for the radiation treatment planning with the lung phantom and internal mammary node cases. The discrepancies might come from the limitations of the clinical TPS, which is the inaccurate dose calculation algorithm for the scattering effect, in the range compensator and inhomogeneous material. Moreover, the steep slope of the compensator, conversion of the HU values to the human phantom, and the dose calculation algorithm for the HU assignment also could be reasons of the discrepancies. The current study could be used for the independent dose validation of treatment plans including high inhomogeneities, the steep compensator, and riskiness such as lung, head & neck cases. According to the treatment policy, the dose discrepancies predicted with MC could be used for the acceptance decision of the original treatment plan.

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs

PubMed Central

Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-01-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day. PMID:25874036

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs.

PubMed

Nam, Chunja; Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-03-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

[Acute toxicity of bemithyl and bromithyl].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2000-01-01

The experiments on rats showed for bemithyl LD50 = 581.48 (350.17-965.57) mg/kg and for bromithyl LD50 = 1750.30 (1463.07-2093.92) mg/kg (males) and 1584.29 (1280.46-1960.22) mg/kg (females). The therapeutic ratios are 4-6 for both drugs, while the toxicity index is 10-15 for bemithyl and 20 <196> 22 for bromithyl. It was established that ergotropic effects prevail in the toxicity of bemithyl administered in the 20-80 mg/kg dose range, while trophotropic effects are dominating at doses above 100 mg/kg. Bromithyl exhibits a dose-dependent trophotropic effect in the entire dose range.

Performance of Al2O3:C optically stimulated luminescence dosimeters for clinical radiation therapy applications.

PubMed

Hu, B; Wang, Y; Zealey, W

2009-12-01

A commercial Optical Stimulated Luminescence (OSL) dosimetry system developed by Landauer was tested to analyse the possibility of using OSL dosimetry for external beam radiotherapy planning checks. Experiments were performed to determine signal sensitivity, dose response range, beam type/energy dependency, reproducibility and linearity. Optical annealing processes to test OSL material reusability were also studied. In each case the measurements were converted into absorbed dose. The experimental results show that OSL dosimetry provides a wide dose response range, good linearity and reproducibility for the doses up to 800cGy. The OSL output is linear with dose up to 600cGy range showing a maximum deviation from linearity of 2.0% for the doses above 600cGy. The standard deviation in response of 20 dosimeters was 3.0%. After optical annealing using incandescent light, the readout intensity decreased by approximately 98% in the first 30 minutes. The readout intensity, I, decreased after repeated optical annealing as a power law, given by I infinity t (-1.3). This study concludes that OSL dosimetry can provide an alternative dosimetry technique for use in in-vivo dosimetry if rigorous measurement protocols are established.

Individual variation in botulism.

PubMed Central

Smith, G. R.

1986-01-01

Mice were treated per os with one oral LD100 of toxic filtrate from a culture of Clostridium botulinum type C. The period between dosing and the first appearance of clinical signs varied greatly (2-31 h) from one animal to another. The duration of the pre-clinical and clinical phases together ranged from 5.5 to greater than 55 h. The duration of the clinical phase alone ranged from 1.25 to greater than 24 h, except for a minority of mice in which death occurred suddenly from apparent heart failure with no premonitory signs 4.75-31 h after dosing. Toxaemia was demonstrable in all mice that had just begun to show a clinical response 3.75-6.5 h after dosing, and in some that had not. Outside these time limits toxaemia was demonstrable only rarely, and beyond 12 h after dosing never. Therefore the many (approximately 50%) mice that began to show clinical signs more than 12 h after dosing had no demonstrable toxaemia throughout the entire clinical phase of the disease. The concentrations of toxin demonstrated in the blood ranged from less than 5 to greater than or equal to 20 (but less than 40) intravenous mouse-lethal doses/ml. PMID:3741778

Dosimetric characteristics of a MOSFET dosimeter for clinical electron beams.

PubMed

Manigandan, D; Bharanidharan, G; Aruna, P; Devan, K; Elangovan, D; Patil, Vikram; Tamilarasan, R; Vasanthan, S; Ganesan, S

2009-09-01

The fundamental dosimetric characteristics of commercially available metal oxide semiconductor field effect transistor (MOSFET) detectors were studied for clinical electron beam irradiations. MOSFET showed excellent linearity against doses measured using an ion chamber in the dose range of 20-630cGy. MOSFET reproducibility is better at high doses compared to low doses. The output factors measured with the MOSFET were within +/-3% when compared with those measured with a parallel plate chamber. From 4 to 12MeV, MOSFETs showed a large angular dependence in the tilt directions and less in the axial directions. MOSFETs do not show any dose-rate dependence between 100 and 600MU/min. However, MOSFETs have shown under-response when the dose per pulse of the beam is decreased. No measurable effect in MOSFET response was observed in the temperature range of 23-40 degrees C. The energy dependence of a MOSFET dosimeter was within +/-3.0% for 6-18MeV electron beams and 5.5% for 4MeV ones. This study shows that MOSFET detectors are suitable for dosimetry of electron beams in the energy range of 4-18MeV.

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning.

PubMed

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A

2016-05-01

Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose-volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Radiotherapy dose verification on a customised head and neck perspex phantom

NASA Astrophysics Data System (ADS)

Eng, K. Y.; Kandaiya, S.; Yahaya, N. Z.

2017-05-01

IMRT dose planned for head and neck radiotherapy was verified using a customised acrylic head-and-neck phantom. The dosimeters used were calibrated Gafchromic EBT2 film and metal-oxide-semiconductor-field-effect-transistor (MOSFET). Target volumes (TV) and organs-at-risk (OAR) which were previously contoured by an oncologist on selected nasopharynx (NPC) patients were transferred to this phantom by an image fusion procedure. Three radiotherapy plans were done: Plan1 with 7-fields intensity-modulated radiotherapy (IMRT) of prescribed dose 70 Gy using 33 fractions; Plan2 with 7-fields IMRT plan at 70 Gy and 35 fractions; and Plan3 which was a mid-plane-dose (MPD) plan of 66 Gy at 33 fractions. The dose maps were first verified using MapCheck2 by SNC-PatientTM software. The passing rates from gamma analysis were 97.7% (Plan1), 93.1% (Plan2) and 100% (Plan3). Percentage difference between Treatment Planning System (TPS) calculated dose and MOSFET measured dose was comparatively higher than those from EBT2. Calculated dose and EBT2 measured doses showed differences of within the range of ±3% for TV and <±10% for OARs. However MOSFET had differences of within the range of ±6% for TV and within the range of ±10% for OARs between measured and planned doses. An overdose treatment may occur as TPS calculated doses were lower than the measured doses in these plans. This may be due to the effects of leaf leakage, leaf scatter and photon backscatter into the measuring tools (Pawlicki et al., 1999 and Ma et al., 2000). More IMRT plans have to be studied to validate this conclusion. However, the dose measurements were still within the 10% tolerance (AAPM Task Group 119). In conclusion, both GafchromicEBT2 film and MOSFET are suitable for IMRT radiotherapy dosimetry.

Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms.

PubMed

Koivisto, Juha H; Wolff, Jan E; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-07-08

The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50-90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point-dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k = 2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low-dose limit. The sensitivity was 3.09 ± 0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was -8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD-comparable low-dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low.

SU-F-I-32: Organ Doses from Pediatric Head CT Scan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, H; Liu, Q; Qiu, J

Purpose: To evaluate the organ doses of pediatric patients who undergoing head CT scan using Monte Carlo (MC) simulation and compare it with measurements in anthropomorphic child phantom.. Methods: A ten years old children voxel phantom was developed from CT images, the voxel size of the phantom was 2mm*2mm*2mm. Organ doses from head CT scan were simulated using MCNPX software, 180 detectors were placed in the voxel phantom to tally the doses of the represented tissues or organs. When performing the simulation, 120 kVp and 88 mA were selected as the scan parameters. The scan range covered from the topmore » of the head to the end of the chain, this protocol was used at CT simulator for radiotherapy. To validate the simulated results, organ doses were measured with radiophotoluminescence (RPL) detectors, placed in the 28 organs of the 10 years old CIRS ATOM phantom. Results: The organ doses results matched well between MC simulation and phantom measurements. The eyes dose was showed to be as expected the highest organ dose: 28.11 mGy by simulation and 27.34 mGy by measurement respectively. Doses for organs not included in the scan volume were much lower than those included in the scan volume, thymus doses were observed more than 10 mGy due the CT protocol for radiotherapy covered more body part than routine head CT scan. Conclusion: As the eyes are superficial organs, they may receive the highest radiation dose during the CT scan. Considering the relatively high radio sensitivity, using shielding material or organ based tube current modulation technique should be encouraged to reduce the eye radiation risks. Scan range was one of the most important factors that affects the organ doses during the CT scan. Use as short as reasonably possible scan range should be helpful to reduce the patient radiation dose. This work was supported by the National Natural Science Foundation of China(11475047)« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Islam, M; Ahmad, S; Jin, H

Purpose: The out-of-beam dose is important for understanding the peripheral dose in radiation therapy. In proton radiotherapy, the study of out-of-beam dose is scarce and the treatment planning system (TPS) based on pencil beam algorithm cannot accurately predict the out-of-beam dose. This study investigates the out-of-beam dose for the single-room Mevion S250 double scattering proton therapy system using experimentally measured and treatment planning software generated data. The results are compared with those reported for conventional photon beam therapy. However, this study does not incorporate the neutron contribution in the scattered dose. Methods: A total of seven proton treatment plans weremore » generated using Varian Eclipse TPS for three different sites (brain, lung, and pelvis) in an anthropomorphic phantom. Three field sizes of 5×5, 10×10, and 20×20 cm{sup 2} (lung only) with typical clinical range (13.3–22.8 g/cm{sup 2}) and modulation widths (5.3–14.0 g/cm{sup 2}) were used. A single beam was employed in each treatment plan to deliver a dose of 181.8 cGy (200.0 cGy (RBE)) to the selected target. The out-of-beam dose was measured at 2.0, 5.0, 10.0, and 15.0 cm from the beam edge in the phantom using a thimble chamber (PTW TN31010). Results: The out-of-beam dose generally increased with field size, range, and volume irradiated. For all the plans, the scattered dose sharply fell off with distance. At 2.0 cm, the out-of-beam dose ranged from 0.35% to 2.16% of the delivered dose; however, the dose was clinically negligible (<0.3%) at a distance of 5.0 cm and greater. In photon therapy, the slightly greater out-of-beam dose was reported (TG36; 4%, 2%, and 1% for 2.0, 5.0, and 10.0 cm, respectively, using 6 MV beam). Conclusion: The measured out-of-beam dose in proton therapy excluding neutron contribution was observed higher than the TPS calculated dose and comparable to that of photon beam therapy.« less

Determination of output factors for small proton therapy fields.

PubMed

Fontenot, Jonas D; Newhauser, Wayne D; Bloch, Charles; White, R Allen; Titt, Uwe; Starkschall, George

2007-02-01

Current protocols for the measurement of proton dose focus on measurements under reference conditions; methods for measuring dose under patient-specific conditions have not been standardized. In particular, it is unclear whether dose in patient-specific fields can be determined more reliably with or without the presence of the patient-specific range compensator. The aim of this study was to quantitatively assess the reliability of two methods for measuring dose per monitor unit (DIMU) values for small-field treatment portals: one with the range compensator and one without the range compensator. A Monte Carlo model of the Proton Therapy Center-Houston double-scattering nozzle was created, and estimates of D/MU values were obtained from 14 simulated treatments of a simple geometric patient model. Field-specific D/MU calibration measurements were simulated with a dosimeter in a water phantom with and without the range compensator. D/MU values from the simulated calibration measurements were compared with D/MU values from the corresponding treatment simulation in the patient model. To evaluate the reliability of the calibration measurements, six metrics and four figures of merit were defined to characterize accuracy, uncertainty, the standard deviations of accuracy and uncertainty, worst agreement, and maximum uncertainty. Measuring D/MU without the range compensator provided superior results for five of the six metrics and for all four figures of merit. The two techniques yielded different results primarily because of high-dose gradient regions introduced into the water phantom when the range compensator was present. Estimated uncertainties (approximately 1 mm) in the position of the dosimeter in these regions resulted in large uncertainties and high variability in D/MU values. When the range compensator was absent, these gradients were minimized and D/MU values were less sensitive to dosimeter positioning errors. We conclude that measuring D/MU without the range compensator present provides more reliable results than measuring it with the range compensator in place.

Size-specific dose estimate (SSDE) provides a simple method to calculate organ dose for pediatric CT examinations

PubMed Central

Moore, Bria M.; Brady, Samuel L.; Mirro, Amy E.; Kaufman, Robert A.

2014-01-01

Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) were then multiplied by patient-specific SSDE to estimate patient organ dose. The \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. Individual\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ , was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusions: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ±10%. In addition, this study provides a complete list of organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE. PMID:24989395

Quantities for assessing high photon doses to the body: a calculational approach.

PubMed

Eakins, Jonathan S; Ainsbury, Elizabeth A

2018-06-01

Tissue reactions are the most clinically significant consequences of high-dose exposures to ionising radiation. However, currently there is no universally recognized dose quantity that can be used to assess and report generalised risks to individuals following whole body exposures in the high-dose range. In this work, a number of potential dose quantities are presented and discussed, with mathematical modelling techniques employed to compare them and explore when their differences are most or least manifest. The results are interpreted to propose the average (D GRB ) of the absorbed doses to the stomach, small intestine, red bone marrow, and brain as the optimum quantity for informing assessments of risk. A second, maximally conservative dose quantity (D Max ) is also suggested, which places limits on any under-estimates resulting from the adoption of D GRB . The primary aim of this work is to spark debate, with further work required to refine the final choice of quantity or quantities most appropriate for the full range of different potential exposure scenarios.

Flat Ge-doped optical fibres for food irradiation dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noor, N. Mohd; Jusoh, M. A.; Razis, A. F. Abdull

Exposing food to radiation can improve hygiene quality, germination control, retard sprouting, and enhance physical attributes of the food product. To provide for food safety, radiation dosimetry in irradiated food is required. Herein, fabricated germanium doped (Ge-doped) optical fibres have been used. The fibres have been irradiated using a gamma source irradiator, doses in the range 1 kGy to 10 kGy being delivered. Using Ge-doped optical fibres of variable size, type and dopant concentration, study has been made of linearity, reproducibility, and fading. The thermoluminescence (TL) yield of the fibres were obtained and compared. The fibres exhibit a linear dosemore » response over the investigated range of doses, with mean reproducibility to within 2.69 % to 8.77 %, exceeding the dose range of all commercial dosimeters used in evaluating high doses for the food irradiation industry. TL fading of the Ge-doped flat fibres has been found to be < 13%.« less

Estimation of breast dose reduction potential for organ-based tube current modulated CT with wide dose reduction arc

NASA Astrophysics Data System (ADS)

Fu, Wanyi; Sturgeon, Gregory M.; Agasthya, Greeshma; Segars, W. Paul; Kapadia, Anuj J.; Samei, Ehsan

2017-03-01

This study aimed to estimate the organ dose reduction potential for organ-dose-based tube current modulated (ODM) thoracic CT with wide dose reduction arc. Twenty-one computational anthropomorphic phantoms (XCAT, age range: 27- 75 years, weight range: 52.0-105.8 kg) were used to create a virtual patient population with clinical anatomic variations. For each phantom, two breast tissue compositions were simulated: 50/50 and 20/80 (glandular-to-adipose ratio). A validated Monte Carlo program was used to estimate the organ dose for standard tube current modulation (TCM) (SmartmA, GE Healthcare) and ODM (GE Healthcare) for a commercial CT scanner (Revolution, GE Healthcare) with explicitly modeled tube current modulation profile, scanner geometry, bowtie filtration, and source spectrum. Organ dose was determined using a typical clinical thoracic CT protocol. Both organ dose and CTDIvol-to-organ dose conversion coefficients (h factors) were compared between TCM and ODM. ODM significantly reduced all radiosensitive organ doses (p<0.01). The breast dose was reduced by 30+/-2%. For h factors, organs in the anterior region (e.g. thyroid, stomach) exhibited substantial decreases, and the medial, distributed, and posterior region either saw an increase or no significant change. The organ-dose-based tube current modulation significantly reduced organ doses especially for radiosensitive superficial anterior organs such as the breasts.

Tumor Control Outcomes Following Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases from Renal Cell Carcinoma

PubMed Central

Zelefsky, Michael J; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei, Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

2014-01-01

Purpose To report tumor local progression-free outcomes following treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Methods and Materials Between 2004 and 2010, a total of 105 lesions from renal cell carcinomas were treated with either SD-IGRT to prescription doses of 18–24 Gy (median, 24 Gy) or hypofractionation (3 or 5 fractions) with prescription doses ranging between 20 and 30 Gy. The median follow-up was 12 months (range, 1–48 months). Results The overall 3-year actuarial local progression-free survival (LPFS) for all lesions was 44%. The 3-year LPFS for those who received high single-dose (24 Gy; n = 45), low single-dose (< 24 Gy; n = 14), and hypofractionation regimens (n = 46) were 88%, 21%, and 17%, respectively (high single dose versus low single dose, p = 0.001; high single dose versus hypofractionation, p < 0.001). Multivariate analysis revealed the following variables as significant predictors of improved LPFS: dose of 24 Gy compared with lower dose (p = 0.009), and single dose versus hypofractionation (p = 0.008). Conclusion High-dose SD-IGRT is a non-invasive procedure resulting in high probability of local tumor control for metastatic renal cell cancers, generally considered radioresistant according to classical radiobiological ranking. PMID:21596489

Organ doses for reference adult male and female undergoing computed tomography estimated by Monte Carlo simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel

2011-03-15

Purpose: To develop a computed tomography (CT) organ dose estimation method designed to readily provide organ doses in a reference adult male and female for different scan ranges to investigate the degree to which existing commercial programs can reasonably match organ doses defined in these more anatomically realistic adult hybrid phantomsMethods: The x-ray fan beam in the SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code MCNPX2.6. The simulated CT scanner model was validated through comparison with experimentally measured lateral free-in-air dose profiles and computed tomography dose index (CTDI) values. The reference adult malemore » and female hybrid phantoms were coupled with the established CT scanner model following arm removal to simulate clinical head and other body region scans. A set of organ dose matrices were calculated for a series of consecutive axial scans ranging from the top of the head to the bottom of the phantoms with a beam thickness of 10 mm and the tube potentials of 80, 100, and 120 kVp. The organ doses for head, chest, and abdomen/pelvis examinations were calculated based on the organ dose matrices and compared to those obtained from two commercial programs, CT-EXPO and CTDOSIMETRY. Organ dose calculations were repeated for an adult stylized phantom by using the same simulation method used for the adult hybrid phantom. Results: Comparisons of both lateral free-in-air dose profiles and CTDI values through experimental measurement with the Monte Carlo simulations showed good agreement to within 9%. Organ doses for head, chest, and abdomen/pelvis scans reported in the commercial programs exceeded those from the Monte Carlo calculations in both the hybrid and stylized phantoms in this study, sometimes by orders of magnitude. Conclusions: The organ dose estimation method and dose matrices established in this study readily provides organ doses for a reference adult male and female for different CT scan ranges and technical parameters. Organ doses from existing commercial programs do not reasonably match organ doses calculated for the hybrid phantoms due to differences in phantom anatomy, as well as differences in organ dose scaling parameters. The organ dose matrices developed in this study will be extended to cover different technical parameters, CT scanner models, and various age groups.« less

Systemic levels of local anaesthetic after intra-peritoneal application--a systematic review.

PubMed

Kahokehr, A; Sammour, T; Vather, R; Taylor, M; Stapelberg, F; Hill, A G

2010-07-01

There is a lack of cohesive reports on the systemic levels of local anaesthetic after intraperitoneal application. A comprehensive systematic review with no language restriction was conducted. Eighteen suitable articles were identified. Data were compiled and presented according to local anaesthetic agent. Intraperitoneal local anaesthetic has been studied in many different procedures, including open and laparoscopic surgery. A total of 415 patients were included for analysis. There were no cases of clinical toxicity. There were 11 (2.7%) cases with a systemic level above or close to a safe threshold (as determined by the report authors) in three trials utilising intraperitoneal local anaesthetic after laparoscopic cholecystectomy. Intraperitoneal lignocaine doses varied from 100 to 1000 mg, mean Cmax ranged from 1.01 to 4.32 microg/ml and mean Tmax ranged from 15 to 40 minutes. Intraperitoneal bupivacaine doses varied from 50 to 150 mg (weight based doses also reported), mean Cmax ranged from 0.29 to 1.14 microg/ml and mean Tmax ranged from 15 to 60 minutes. Intraperitoneal ropivacaine doses varied from 100 to 300 mg, mean Cmax ranged from 0.66 to 3.76 microg/ml and mean Tmax ranged from 15 to 35 minutes. The addition of adrenaline to intraperitoneal local anaesthetic almost halves systemic levels and prolongs Tmax. Intraperitoneal local anaesthetic results in detectable systemic levels in the perioperative setting. Despite a lack of clinical toxicity, careful attention to dose is still required to prevent potential systemic toxic levels. Clinicians should also consider the addition of adrenaline to intraperitoneal local anaesthetic solutions to further add to the systemic safety profile.

Pharmacologically active phenylpropanoids from Senra incana.

PubMed

Farah, M H; Samuelsson, G

1992-02-01

Coniferaldehyde, scopoletin, sinapaldehyde, and syringaldehyde were isolated from an aqueous extract of Senra incana. All four compounds inhibited prostaglandin synthetase in a dose-dependent way. Compared to aspirin, the potency of coniferaldehyde and scopoletin was about five times higher, whereas syringaldehyde and sinapaldehyde had about half the potency of this reference compound. On topical application, sinapaldehyde and scopoletin dose-dependently inhibited ethyl phenylpropiolate-induced edema of the rat ear. The active dose range was 1-10 micrograms/ear. Higher doses had a lower effect. Syringaldehyde was active in the range 20-100 micrograms/ear, whereas the effect of coniferaldehyde was inconclusive. Coniferaldehyde and sinapaldehyde inhibited electrically induced contractions of the guinea pig ileum in a dose-dependent way. Syringaldehyde showed a weak inhibition at a concentration of 550 microM.

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose.

PubMed

Andrews, Louise M; de Winter, Brenda C M; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H N; Koch, Birgit C P; van Gelder, Teun; Hesselink, Dennis A

2017-02-01

Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients.

Validation of a Low Dose Simulation Technique for Computed Tomography Images

PubMed Central

Muenzel, Daniela; Koehler, Thomas; Brown, Kevin; Žabić, Stanislav; Fingerle, Alexander A.; Waldt, Simone; Bendik, Edgar; Zahel, Tina; Schneider, Armin; Dobritz, Martin; Rummeny, Ernst J.; Noël, Peter B.

2014-01-01

Purpose Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT) images from an original higher dose scan. Materials and Methods Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV) of a swine were acquired (approved by the regional governmental commission for animal protection). Simulations of CT acquisition with a lower dose (simulated 10–80 mAs) were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. Results Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was −1.2% (range −9% to 3.2%) and −0.2% (range −8.2% to 3.2%), respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9–10.2 HU (noise) and 1.9–13.4 HU (CT values), without significant differences (p>0.05). Subjective observer evaluation of image appearance showed no visually detectable difference. Conclusion Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques. PMID:25247422

Verification of calculated skin doses in postmastectomy helical tomotherapy.

PubMed

Ito, Shima; Parker, Brent C; Levine, Renee; Sanders, Mary Ella; Fontenot, Jonas; Gibbons, John; Hogstrom, Kenneth

2011-10-01

To verify the accuracy of calculated skin doses in helical tomotherapy for postmastectomy radiation therapy (PMRT). In vivo thermoluminescent dosimeters (TLDs) were used to measure the skin dose at multiple points in each of 14 patients throughout the course of treatment on a TomoTherapy Hi·Art II system, for a total of 420 TLD measurements. Five patients were evaluated near the location of the mastectomy scar, whereas 9 patients were evaluated throughout the treatment volume. The measured dose at each location was compared with calculations from the treatment planning system. The mean difference and standard error of the mean difference between measurement and calculation for the scar measurements was -1.8% ± 0.2% (standard deviation [SD], 4.3%; range, -11.1% to 10.6%). The mean difference and standard error of the mean difference between measurement and calculation for measurements throughout the treatment volume was -3.0% ± 0.4% (SD, 4.7%; range, -18.4% to 12.6%). The mean difference and standard error of the mean difference between measurement and calculation for all measurements was -2.1% ± 0.2% (standard deviation, 4.5%: range, -18.4% to 12.6%). The mean difference between measured and calculated TLD doses was statistically significant at two standard deviations of the mean, but was not clinically significant (i.e., was <5%). However, 23% of the measured TLD doses differed from the calculated TLD doses by more than 5%. The mean of the measured TLD doses agreed with TomoTherapy calculated TLD doses within our clinical criterion of 5%. Copyright © 2011 Elsevier Inc. All rights reserved.

Verification of Calculated Skin Doses in Postmastectomy Helical Tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ito, Shima; Parker, Brent C., E-mail: bcparker@marybird.com; Mary Bird Perkins Cancer Center, Baton Rouge, LA

2011-10-01

Purpose: To verify the accuracy of calculated skin doses in helical tomotherapy for postmastectomy radiation therapy (PMRT). Methods and Materials: In vivo thermoluminescent dosimeters (TLDs) were used to measure the skin dose at multiple points in each of 14 patients throughout the course of treatment on a TomoTherapy Hi.Art II system, for a total of 420 TLD measurements. Five patients were evaluated near the location of the mastectomy scar, whereas 9 patients were evaluated throughout the treatment volume. The measured dose at each location was compared with calculations from the treatment planning system. Results: The mean difference and standard errormore » of the mean difference between measurement and calculation for the scar measurements was -1.8% {+-} 0.2% (standard deviation [SD], 4.3%; range, -11.1% to 10.6%). The mean difference and standard error of the mean difference between measurement and calculation for measurements throughout the treatment volume was -3.0% {+-} 0.4% (SD, 4.7%; range, -18.4% to 12.6%). The mean difference and standard error of the mean difference between measurement and calculation for all measurements was -2.1% {+-} 0.2% (standard deviation, 4.5%: range, -18.4% to 12.6%). The mean difference between measured and calculated TLD doses was statistically significant at two standard deviations of the mean, but was not clinically significant (i.e., was <5%). However, 23% of the measured TLD doses differed from the calculated TLD doses by more than 5%. Conclusions: The mean of the measured TLD doses agreed with TomoTherapy calculated TLD doses within our clinical criterion of 5%.« less

Continuous Toxicological Dose-Response Relationships Are Pretty Homogeneous (Society for Risk Analysis Annual Meeting)

EPA Science Inventory

Dose-response relationships for a wide range of in vivo and in vitro continuous datasets are well-described by a four-parameter exponential or Hill model, based on a recent analysis of multiple historical dose-response datasets, mostly with more than five dose groups (Slob and Se...

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

PubMed

Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

2015-04-01

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Effect of γ-dose rate and total dose interrelation on the polymeric hydrogel: A novel injectable male contraceptive

NASA Astrophysics Data System (ADS)

Jha, Pradeep K.; Jha, Rakhi; Gupta, B. L.; Guha, Sujoy K.

2010-05-01

Functional necessity to use a particular range of dose rate and total dose of γ-initiated polymerization to manufacture a novel polymeric hydrogel RISUG ® (reversible inhibition of sperm under guidance) made of styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), for its broad biomedical application explores new dimension of research. The present work involves 16 irradiated samples. They were tested by fourier transform infrared spectroscopy, matrix assisted laser desorption/ionization-TOF, field emission scanning electron microscopy, high resolution transmission electron microscopy, etc. to see the interrelation effect of gamma dose rates (8.25, 17.29, 20.01 and 25.00 Gy/min) and four sets of doses (1.8, 2.0, 2.2 and 2.4 kGy) on the molecular weight, molecular weight distribution and porosity analysis of the biopolymeric drug RISUG ®. The results of randomized experiment indicated that a range of 18-24 Gy/min γ-dose rate and 2.0-2.4 kGy γ-total doses is suitable for the desirable in vivo performance of the contraceptive copolymer.

Assessment of radiation doses from residential smoke detectors that contain americium-241

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Donnell, F.R.; Etnier, E.L.; Holton, G.A.

1981-10-01

External dose equivalents and internal dose commitments were estimated for individuals and populations from annual distribution, use, and disposal of 10 million ionization chamber smoke detectors that contain 110 kBq (3 ..mu..Ci) americium-241 each. Under exposure scenarios developed for normal distribution, use, and disposal using the best available information, annual external dose equivalents to average individuals were estimated to range from 4 fSv (0.4 prem) to 20 nSv (2 ..mu..rem) for total body and from 7 fSv to 40 nSv for bone. Internal dose commitments to individuals under post disposal scenarios were estimated to range from 0.006 to 80 ..mu..Svmore » (0.0006 to 8 mrem) to total body and from 0.06 to 800 ..mu..Sv to bone. The total collective dose (the sum of external dose equivalents and 50-year internal dose commitments) for all individuals involved with distribution, use, or disposal of 10 million smoke detectors was estimated to be about 0.38 person-Sv (38 person-rem) to total body and 00 ft/sup 2/).« less

Limitations of analytical dose calculations for small field proton radiosurgery.

PubMed

Geng, Changran; Daartz, Juliane; Lam-Tin-Cheung, Kimberley; Bussiere, Marc; Shih, Helen A; Paganetti, Harald; Schuemann, Jan

2017-01-07

The purpose of the work was to evaluate the dosimetric uncertainties of an analytical dose calculation engine and the impact on treatment plans using small fields in intracranial proton stereotactic radiosurgery (PSRS) for a gantry based double scattering system. 50 patients were evaluated including 10 patients for each of 5 diagnostic indications of: arteriovenous malformation (AVM), acoustic neuroma (AN), meningioma (MGM), metastasis (METS), and pituitary adenoma (PIT). Treatment plans followed standard prescription and optimization procedures for PSRS. We performed comparisons between delivered dose distributions, determined by Monte Carlo (MC) simulations, and those calculated with the analytical dose calculation algorithm (ADC) used in our current treatment planning system in terms of dose volume histogram parameters and beam range distributions. Results show that the difference in the dose to 95% of the target (D95) is within 6% when applying measured field size output corrections for AN, MGM, and PIT. However, for AVM and METS, the differences can be as great as 10% and 12%, respectively. Normalizing the MC dose to the ADC dose based on the dose of voxels in a central area of the target reduces the difference of the D95 to within 6% for all sites. The generally applied margin to cover uncertainties in range (3.5% of the prescribed range  +  1 mm) is not sufficient to cover the range uncertainty for ADC in all cases, especially for patients with high tissue heterogeneity. The root mean square of the R90 difference, the difference in the position of distal falloff to 90% of the prescribed dose, is affected by several factors, especially the patient geometry heterogeneity, modulation and field diameter. In conclusion, implementation of Monte Carlo dose calculation techniques into the clinic can reduce the uncertainty of the target dose for proton stereotactic radiosurgery. If MC is not available for treatment planning, using MC dose distributions to adjust the delivered doses level can also reduce uncertainties below 3% for mean target dose and 6% for the D95.

Peak skin and eye lens radiation dose from brain perfusion CT based on Monte Carlo simulation.

PubMed

Zhang, Di; Cagnon, Chris H; Villablanca, J Pablo; McCollough, Cynthia H; Cody, Dianna D; Stevens, Donna M; Zankl, Maria; Demarco, John J; Turner, Adam C; Khatonabadi, Maryam; McNitt-Gray, Michael F

2012-02-01

The purpose of our study was to accurately estimate the radiation dose to skin and the eye lens from clinical CT brain perfusion studies, investigate how well scanner output (expressed as volume CT dose index [CTDI(vol)]) matches these estimated doses, and investigate the efficacy of eye lens dose reduction techniques. Peak skin dose and eye lens dose were estimated using Monte Carlo simulation methods on a voxelized patient model and 64-MDCT scanners from four major manufacturers. A range of clinical protocols was evaluated. CTDI(vol) for each scanner was obtained from the scanner console. Dose reduction to the eye lens was evaluated for various gantry tilt angles as well as scan locations. Peak skin dose and eye lens dose ranged from 81 mGy to 348 mGy, depending on the scanner and protocol used. Peak skin dose and eye lens dose were observed to be 66-79% and 59-63%, respectively, of the CTDI(vol) values reported by the scanners. The eye lens dose was significantly reduced when the eye lenses were not directly irradiated. CTDI(vol) should not be interpreted as patient dose; this study has shown it to overestimate dose to the skin or eye lens. These results may be used to provide more accurate estimates of actual dose to ensure that protocols are operated safely below thresholds. Tilting the gantry or moving the scanning region further away from the eyes are effective for reducing lens dose in clinical practice. These actions should be considered when they are consistent with the clinical task and patient anatomy.

Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses

PubMed Central

Colborn, Theo; Hayes, Tyrone B.; Heindel, Jerrold J.; Jacobs, David R.; Lee, Duk-Hee; Shioda, Toshi; Soto, Ana M.; vom Saal, Frederick S.; Welshons, Wade V.; Zoeller, R. Thomas

2012-01-01

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health. PMID:22419778

Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose

PubMed Central

2013-01-01

Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that associated with the label dose of toceranib. This lower dose range of toceranib should be considered for future use in dogs with cancer. PMID:24079884

Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry.

PubMed

González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

2016-05-01

This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dose ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.

Is It Better to Enter a Volume CT Dose Index Value before or after Scan Range Adjustment for Radiation Dose Optimization of Pediatric Cardiothoracic CT with Tube Current Modulation?

PubMed Central

2018-01-01

Objective To determine whether the body size-adapted volume computed tomography (CT) dose index (CTDvol) in pediatric cardiothoracic CT with tube current modulation is better to be entered before or after scan range adjustment for radiation dose optimization. Materials and Methods In 83 patients, cardiothoracic CT with tube current modulation was performed with the body size-adapted CTDIvol entered after (group 1, n = 42) or before (group 2, n = 41) scan range adjustment. Patient-related, radiation dose, and image quality parameters were compared and correlated between the two groups. Results The CTDIvol after the CT scan in group 1 was significantly higher than that in group 2 (1.7 ± 0.1 mGy vs. 1.4 ± 0.3 mGy; p < 0.0001). Image noise (4.6 ± 0.5 Hounsfield units [HU] vs. 4.5 ± 0.7 HU) and image quality (1.5 ± 0.6 vs. 1.5 ± 0.6) showed no significant differences between the two (p > 0.05). In both groups, all patient-related parameters, except body density, showed positive correlations (r = 0.49–0.94; p < 0.01) with the CTDIvol before and after the CT scan. The CTDIvol after CT scan showed modest positive correlation (r = 0.49; p ≤ 0.001) with image noise in group 1 but no significant correlation (p > 0.05) in group 2. Conclusion In pediatric cardiothoracic CT with tube current modulation, the CTDIvol entered before scan range adjustment provides a significant dose reduction (18%) with comparable image quality compared with that entered after scan range adjustment.

A multicenter study of plasma use in the United States.

PubMed

Triulzi, Darrell; Gottschall, Jerome; Murphy, Edward; Wu, Yanyun; Ness, Paul; Kor, Daryl; Roubinian, Nareg; Fleischmann, Debra; Chowdhury, Dhuly; Brambilla, Donald

2015-06-01

Detailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy. Ten US hospitals collected detailed medical information from the electronic health records for 1 year (2010-2011) for all adult patients transfused with plasma. A total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2-4; range 1-72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5-12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%-75% interquartile range, 1.6-2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4-2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%). This large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used. © 2014 AABB.

Clinical commissioning of an in vivo range verification system for prostate cancer treatment with anterior and anterior oblique proton beams

NASA Astrophysics Data System (ADS)

Hoesl, M.; Deepak, S.; Moteabbed, M.; Jassens, G.; Orban, J.; Park, Y. K.; Parodi, K.; Bentefour, E. H.; Lu, H. M.

2016-04-01

The purpose of this work is the clinical commissioning of a recently developed in vivo range verification system (IRVS) for treatment of prostate cancer by anterior and anterior oblique proton beams. The IRVS is designed to perform a complete workflow for pre-treatment range verification and adjustment. It contains specifically designed dosimetry and electronic hardware and a specific software for workflow control with database connection to the treatment and imaging systems. An essential part of the IRVS system is an array of Si-diode detectors, designed to be mounted to the endorectal water balloon routinely used for prostate immobilization. The diodes can measure dose rate as function of time from which the water equivalent path length (WEPL) and the dose received are extracted. The former is used for pre-treatment beam range verification and correction, if necessary, while the latter is to monitor the dose delivered to patient rectum during the treatment and serves as an additional verification. The entire IRVS workflow was tested for anterior and 30 degree inclined proton beam in both solid water and anthropomorphic pelvic phantoms, with the measured WEPL and rectal doses compared to the treatment plan. Gafchromic films were also used for measurement of the rectal dose and compared to IRVS results. The WEPL measurement accuracy was in the order of 1 mm and after beam range correction, the dose received by the rectal wall were 1.6% and 0.4% from treatment planning, respectively, for the anterior and anterior oblique field. We believe the implementation of IRVS would make the treatment of prostate with anterior proton beams more accurate and reliable.

Accuracy and Radiation Dose Reduction of Limited-Range CT in the Evaluation of Acute Appendicitis in Pediatric Patients.

PubMed

Jin, Michael; Sanchez, Thomas R; Lamba, Ramit; Fananapazir, Ghaneh; Corwin, Michael T

2017-09-01

The purpose of this article is to determine the accuracy and radiation dose reduction of limited-range CT prescribed from the top of L2 to the top of the pubic symphysis in children with suspected acute appendicitis. We performed a retrospective study of 210 consecutive pediatric patients from December 11, 2012, through December 11, 2014, who underwent abdominopelvic CT for suspected acute appendicitis. Two radiologists independently reviewed the theoretic limited scans from the superior L2 vertebral body to the top of the pubic symphysis, to assess for visualization of the appendix, acute appendicitis, alternative diagnoses, and incidental findings. Separately, the same parameters were assessed on the full scan by the same two reviewers. Whole-body effective doses were determined for the full- and limited-range scans and were compared using the paired t test. The appendix or entire cecum was visualized on the limited scan in all cases, and no cases of acute appendicitis were missed on the simulated limited scan compared with the full scan. Two alternative diagnoses were missed with the limited scan: one case of hydronephrosis and one of acute acalculous cholecystitis. The mean effective dose for the original scan was 5.6 mSv and that for the simulated limited scan was 3.0 mSv, resulting in a dose reduction of 46.4% (p < 0.001). A limited-range CT examination performed from the top of L2 to the top of the pubic symphysis is as accurate as a full-range abdominopelvic CT in evaluating pediatric patients with suspected appendicitis and reduces the dose by approximately 46%.

Contralateral Breast Dose After Whole-Breast Irradiation: An Analysis by Treatment Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Terence M.; Moran, Jean M., E-mail: jmmoran@med.umich.edu; Hsu, Shu-Hui

2012-04-01

Purpose: To investigate the contralateral breast dose (CBD) across a continuum of breast-conservation therapy techniques. Methods and Materials: An anthropomorphic phantom was CT-simulated, and six treatment plans were generated: open tangents, tangents with an external wedge on the lateral beam, tangents with lateral and medial external wedges, a simple segment plan (three segments per tangent), a complex segmental intensity-modulated radiotherapy (IMRT) plan (five segments per tangent), and a beamlet IMRT plan (>100 segments). For all techniques, the breast on the phantom was irradiated to 5000 cGy. Contralateral breast dose was measured at a uniform depth at the center and eachmore » quadrant using thermoluminescent detectors. Results: Contralateral breast dose varied with position and was 50 {+-} 7.3 cGy in the inner half, 24 {+-} 4.1 cGy at the center, and 16 {+-} 2.2 cGy in the outer half for the open tangential plan. Compared with an average dose of 31 cGy across all points for the open field, the average doses were simple segment 32 cGy (range, 99-105% compared with open technique), complex segment 34 cGy (range, 103-117% compared with open technique), beamlet IMRT 34 cGy (range, 103-124% compared with open technique), lateral wedge only 46 cGy (range, 133-175% compared with open technique), and medial and lateral wedge 96 cGy (range, 282-370% compared with open technique). Conclusions: Single or dual wedge techniques resulted in the highest CBD increases compared with open tangents. To obtain the desired homogeneity to the treated breast while minimizing CBD, segmental and IMRT techniques should be encouraged over external physical compensators.« less

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

PubMed

Mourad, Waleed F; Young, Brett M; Young, Rebekah; Blakaj, Dukagjin M; Ohri, Nitin; Shourbaji, Rania A; Manolidis, Spiros; Gámez, Mauricio; Kumar, Mahesh; Khorsandi, Azita; Khan, Majid A; Shasha, Daniel; Blakaj, Adriana; Glanzman, Jonathan; Garg, Madhur K; Hu, Kenneth S; Kalnicki, Shalom; Harrison, Louis B

2013-09-01

Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. Published by Elsevier Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battum, LJ van; Heukelom, S

Purpose This study investigates the origin of lateral optical density (OD) variation for Gafchromic film (EBT and EBT2) scanned in transmission mode with Epson flatbed scanners (1680 Expression Pro and 10000XL). Effects investigated are: cross talk, optical path length and polarization. Methods Cross talk has been examined with triangular shaped light-transmission sheets with OD ranging from 0 to opaque. Optical path length has been studied with absorptive and reflective OD-filters (OD range 0.2 to 2.0). Dependency on light-polarization on the scanner read out has been investigated using linear polarizer sheets. All experiments have been performed at centre scanner position (normmore » point) and at several lateral scan positions, without and with (un)irradiated EBT-film. Dose values used ranged between 0.2 to 9 Gy, yielding an OD-range between 0.25 to 1.1. Results The lateral OD variation is dose dependent and increases up to 14% at most lateral position for dose up to 9 Gy. Cross talk effect contributes to 0.5% in clinical used OD ranges but equals 2% for extreme high dose gradients. Film induced optical path length will effect the lateral OD variation up to 3% at most lateral points. Light polarization is inherent present in these scanners due to multiple reflection on mirrors. In addition film induced polarization is the most important effect generating the observed lateral OD variation. Both Gafchromic film base and sensitive layer have polarizing capabilities; for the sensitive layer its influence is dose dependent. Conclusions Lateral OD variation origins from optical physics (i.e. polarization and reflection) related to scanner and film construction. Cross talk can be ignored in film dosimetry for clinical used dose values and gradients. Therefore it is recommended to determine the lateral OD variation per film type and scanner.« less

A multicenter study of plasma use in the United States

PubMed Central

Triulzi, Darrell; Gottschall, Jerome; Murphy, Edward; Wu, Yanyun; Ness, Paul; Kor, Daryl; Roubinian, Nareg; Fleischmann, Debra; Chowdhury, Dhuly; Brambilla, Donald

2016-01-01

Background Detailed information regarding plasma use in the United States is needed to identify opportunities for practice improvement and design of clinical trials of plasma therapy. Study Design and Methods Ten US hospitals collected detailed medical information from the electronic health records for 1 year (2010-2011) for all adult patients transfused with plasma. Results A total of 72,167 units of plasma were transfused in 19,596 doses to 9269 patients. The median dose of plasma was 2 units (interquartile range, 2-4; range 1-72); 15% of doses were 1 unit, and 45% were 2 units. When adjusted by patient body weight (kg), the median dose was 7.3 mL/kg (interquartile range, 5.5-12.0). The median pretransfusion international normalized ratio (INR) was 1.9 (25%-75% interquartile range, 1.6-2.6). A total of 22.5% of plasma transfusions were given to patients with an INR of less than 1.6 and 48.5% for an INR of 2.0 or more. The median posttransfusion INR was 1.6 (interquartile range, 1.4-2.0). Only 42% of plasma transfusions resulted in a posttransfusion INR of less than 1.6. Correction of INR increased as the plasma dose increased from 1 to 4 units (p < 0.001). There was no difference in the INR response to different types of plasma. The most common issue locations were general ward (38%) and intensive care unit (ICU; 42%). Conclusion This large database describing plasma utilization in the United States provides evidence for both inadequate dosing and unnecessary transfusion. Measures to improve plasma transfusion practice and clinical trials should be directed at patients on medical and surgical wards and in the ICU where plasma is most commonly used. PMID:25522888

Arterial gastroduodenal infusion of cholecystokinin-33 stimulates the exocrine pancreatic enzyme release via an enteropancreatic reflex, without affecting the endocrine insulin secretion in pigs.

PubMed

Rengman, Sofia; Weström, Björn; Ahrén, Bo; Pierzynowski, Stefan G

2009-03-01

Cholecystokinin (CCK)-dependent exocrine pancreatic regulation seems to involve different pathways in different species. The aims were to explore the enteropancreatic reflex in the CCK-mediated regulation of the exocrine pancreas and to evaluate a possible involvement of this reflex in the endocrine insulin release. In anesthetized pigs, CCK-33 in increasing doses (4-130 pmol kg 10 min) was infused locally to the gastroduodenal artery, or systemically via the jugular vein. Also, a low CCK-33 dose (13 pmol kg) was injected to the duodenum/antrum area before and after a bilateral truncal vagotomy. Cholecystokinin-33 in the physiological dose range 4 to 32 pmol kg 10 min increased protein and trypsin outputs after local infusion to the antral-duodenal area, whereas it had no effect after systemic infusion. Cholecystokinin-33 in the pharmacological dose range 64 to 130 pmol kg 10 min further increased the secretion after both local and systemic infusions. Only CCK-33 infusions in the pharmacological dose range were able to elevate the plasma insulin levels. Vagotomy had no effect on CCK-33-mediated stimulation of the enzyme release, whereas it had a significant effect on the plasma insulin level. Cholecystokinin-33 in the physiological dose range 4 to 32 pmol kg 10 min stimulates the enzyme secretion but had no effect on the insulin release via a short enteropancreatic pathway in pigs.

Phase I Dose Escalation Trial of Vandetanib With Fractionated Radiosurgery in Patients With Recurrent Malignant Gliomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fields, Emma C.; Damek, Denise; Gaspar, Laurie E.

2012-01-01

Purpose: To determine the maximum tolerated dose (MTD) of vandetanib with fractionated stereotactic radiosurgery (SRS) in patients with recurrent malignant gliomas. Methods and Materials: Patients with a recurrent malignant glioma and T1-enhancing recurrent tumor {<=}6 cm were eligible. Vandetanib was given orally, once per day, 7 days a week, starting at least 7 days before SRS and continued until a dose-limiting toxicity (DLT) or disease progression. The planned vandetanib daily dose was 100 mg, 200 mg, and 300 mg for the cohorts 1, 2, and 3, respectively, and was escalated using a standard 3+3 design. A total SRS dose ofmore » 36 Gy, 12 Gy per fraction, was delivered over 3 consecutive days. The MTD was defined as the dose of vandetanib at which less than 33% of patients developed DLTs, defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3 as any Grade 3 or greater nonhematologic toxicity and Grade 4 or greater hematologic toxicity. Results: Ten patients were treated, 6 on cohort 1 and 4 on cohort 2. Treatment characteristics were: 7 men, 3 women; median age, 40 years (range, 22-72); 7 GBM, 3 anaplastic astrocytoma (AA); median initial radiation (RT) dose, 60 Gy (range, 59.4-70); median interval since initial RT, 14.5 months (range, 7-123); All patients received SRS per protocol. The median follow-up time was 4 months (range, 1-10 months). Median time on vandetanib was 3 months (range 1-11). One of 6 patients in the first cohort developed a DLT of Grade 3 hemothorax while on anticoagulation. The MTD was reached when 2 of the 4 patients enrolled in the second cohort developed DLTs. Six patients had radiographic response, 2 with stable disease. Conclusion: The MTD of vandetanib, with SRS in recurrent malignant glioma, is 100 mg daily. Further evaluation of safety and efficacy is warranted.« less

A Monte Carlo study on quantifying the amount of dose reduction by shielding the superficial organs of an Iranian 11-year-old boy

PubMed Central

Akhlaghi, Parisa; Hoseinian-Azghadi, Elie; Miri-Hakimabad, Hashem; Rafat-Motavalli, Laleh

2016-01-01

A method for minimizing organ dose during computed tomography examinations is the use of shielding to protect superficial organs. There are some scientific reports that usage of shielding technique reduces the surface dose to patients with no appreciable loss in diagnostic quality. Therefore, in this Monte Carlo study based on the phantom of a 11-year-old Iranian boy, the effect of using an optimized shield on dose reduction to body organs was quantified. Based on the impact of shield on image quality, lead shields with thicknesses of 0.2 and 0.4 mm were considered for organs exposed directly and indirectly in the scan range, respectively. The results showed that there is 50%–62% reduction in amounts of dose for organs located fully or partly in the scan range at different tube voltages and modeling the true location of all organs in human anatomy, especially the ones located at the border of the scan, range affects the results up to 49%. PMID:28144117

SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, C; Schultheiss, T

Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) weremore » used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.« less

A comprehensive study on the relationship between the image quality and imaging dose in low-dose cone beam CT

NASA Astrophysics Data System (ADS)

Yan, Hao; Cervino, Laura; Jia, Xun; Jiang, Steve B.

2012-04-01

While compressed sensing (CS)-based algorithms have been developed for the low-dose cone beam CT (CBCT) reconstruction, a clear understanding of the relationship between the image quality and imaging dose at low-dose levels is needed. In this paper, we qualitatively investigate this subject in a comprehensive manner with extensive experimental and simulation studies. The basic idea is to plot both the image quality and imaging dose together as functions of the number of projections and mAs per projection over the whole clinically relevant range. On this basis, a clear understanding of the tradeoff between the image quality and imaging dose can be achieved and optimal low-dose CBCT scan protocols can be developed to maximize the dose reduction while minimizing the image quality loss for various imaging tasks in image-guided radiation therapy (IGRT). Main findings of this work include (1) under the CS-based reconstruction framework, image quality has little degradation over a large range of dose variation. Image quality degradation becomes evident when the imaging dose (approximated with the x-ray tube load) is decreased below 100 total mAs. An imaging dose lower than 40 total mAs leads to a dramatic image degradation, and thus should be used cautiously. Optimal low-dose CBCT scan protocols likely fall in the dose range of 40-100 total mAs, depending on the specific IGRT applications. (2) Among different scan protocols at a constant low-dose level, the super sparse-view reconstruction with the projection number less than 50 is the most challenging case, even with strong regularization. Better image quality can be acquired with low mAs protocols. (3) The optimal scan protocol is the combination of a medium number of projections and a medium level of mAs/view. This is more evident when the dose is around 72.8 total mAs or below and when the ROI is a low-contrast or high-resolution object. Based on our results, the optimal number of projections is around 90 to 120. (4) The clinically acceptable lowest imaging dose level is task dependent. In our study, 72.8 mAs is a safe dose level for visualizing low-contrast objects, while 12.2 total mAs is sufficient for detecting high-contrast objects of diameter greater than 3 mm.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Multi-axis dose accumulation of noninvasive image-guided breast brachytherapy through biomechanical modeling of tissue deformation using the finite element method

PubMed Central

Ghadyani, Hamid R.; Bastien, Adam D.; Lutz, Nicholas N.; Hepel, Jaroslaw T.

2015-01-01

Purpose Noninvasive image-guided breast brachytherapy delivers conformal HDR 192Ir brachytherapy treatments with the breast compressed, and treated in the cranial-caudal and medial-lateral directions. This technique subjects breast tissue to extreme deformations not observed for other disease sites. Given that, commercially-available software for deformable image registration cannot accurately co-register image sets obtained in these two states, a finite element analysis based on a biomechanical model was developed to deform dose distributions for each compression circumstance for dose summation. Material and methods The model assumed the breast was under planar stress with values of 30 kPa for Young's modulus and 0.3 for Poisson's ratio. Dose distributions from round and skin-dose optimized applicators in cranial-caudal and medial-lateral compressions were deformed using 0.1 cm planar resolution. Dose distributions, skin doses, and dose-volume histograms were generated. Results were examined as a function of breast thickness, applicator size, target size, and offset distance from the center. Results Over the range of examined thicknesses, target size increased several millimeters as compression thickness decreased. This trend increased with increasing offset distances. Applicator size minimally affected target coverage, until applicator size was less than the compressed target size. In all cases, with an applicator larger or equal to the compressed target size, > 90% of the target covered by > 90% of the prescription dose. In all cases, dose coverage became less uniform as offset distance increased and average dose increased. This effect was more pronounced for smaller target–applicator combinations. Conclusions The model exhibited skin dose trends that matched MC-generated benchmarking results within 2% and clinical observations over a similar range of breast thicknesses and target sizes. The model provided quantitative insight on dosimetric treatment variables over a range of clinical circumstances. These findings highlight the need for careful target localization and accurate identification of compression thickness and target offset. PMID:25829938

SU-E-T-577: Obliquity Factor and Surface Dose in Proton Beam Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, I; Andersen, A; Coutinho, L

2015-06-15

Purpose: The advantage of lower skin dose in proton beam may be diminished creating radiation related sequalae usually seen with photon and electron beams. This study evaluates the surface dose as a complex function of beam parameters but more importantly the effect of beam angle. Methods: Surface dose in proton beam depends on the beam energy, source to surface distance, the air gap between snout and surface, field size, material thickness in front of surface, atomic number of the medium, beam angle and type of nozzle (ie double scattering, (DS), uniform scanning (US) or pencil beam scanning (PBS). Obliquity factormore » (OF) is defined as ratio of surface dose in 0° to beam angle Θ. Measurements were made in water phantom at various beam angles using very small microdiamond that has shown favorable beam characteristics for high, medium and low proton energy. Depth dose measurements were performed in the central axis of the beam in each respective gantry angle. Results: It is observed that surface dose is energy dependent but more predominantly on the SOBP. It is found that as SSD increases, surface dose decreases. In general, SSD, and air gap has limited impact in clinical proton range. High energy has higher surface dose and so the beam angle. The OF rises with beam angle. Compared to OF of 1.0 at 0° beam angle, the value is 1.5, 1.6, 1,7 for small, medium and large range respectively for 60 degree angle. Conclusion: It is advised that just like range and SOBP, surface dose should be clearly understood and a method to reduce the surface dose should be employed. Obliquity factor is a critical parameter that should be accounted in proton beam therapy and a perpendicular beam should be used to reduce surface dose.« less

Spatial Prediction of Coxiella burnetii Outbreak Exposure via Notified Case Counts in a Dose-Response Model.

PubMed

Brooke, Russell J; Kretzschmar, Mirjam E E; Hackert, Volker; Hoebe, Christian J P A; Teunis, Peter F M; Waller, Lance A

2017-01-01

We develop a novel approach to study an outbreak of Q fever in 2009 in the Netherlands by combining a human dose-response model with geostatistics prediction to relate probability of infection and associated probability of illness to an effective dose of Coxiella burnetii. The spatial distribution of the 220 notified cases in the at-risk population are translated into a smooth spatial field of dose. Based on these symptomatic cases, the dose-response model predicts a median of 611 asymptomatic infections (95% range: 410, 1,084) for the 220 reported symptomatic cases in the at-risk population; 2.78 (95% range: 1.86, 4.93) asymptomatic infections for each reported case. The low attack rates observed during the outbreak range from (Equation is included in full-text article.)to (Equation is included in full-text article.). The estimated peak levels of exposure extend to the north-east from the point source with an increasing proportion of asymptomatic infections further from the source. Our work combines established methodology from model-based geostatistics and dose-response modeling allowing for a novel approach to study outbreaks. Unobserved infections and the spatially varying effective dose can be predicted using the flexible framework without assuming any underlying spatial structure of the outbreak process. Such predictions are important for targeting interventions during an outbreak, estimating future disease burden, and determining acceptable risk levels.

Prehospital Care for the Adult and Pediatric Seizure Patient: Current Evidence-based Recommendations.

PubMed

Silverman, Eric C; Sporer, Karl A; Lemieux, Justin M; Brown, John F; Koenig, Kristi L; Gausche-Hill, Marianne; Rudnick, Eric M; Salvucci, Angelo A; Gilbert, Greg H

2017-04-01

We sought to develop evidence-based recommendations for the prehospital evaluation and treatment of adult and pediatric patients with a seizure and to compare these recommendations against the current protocol used by the 33 emergency medical services (EMS) agencies in California. We performed a review of the evidence in the prehospital treatment of patients with a seizure, and then compared the seizure protocols of each of the 33 EMS agencies for consistency with these recommendations. We analyzed the type and route of medication administered, number of additional rescue doses permitted, and requirements for glucose testing prior to medication. The treatment for eclampsia and seizures in pediatric patients were analyzed separately. Protocols across EMS Agencies in California varied widely. We identified multiple drugs, dosages, routes of administration, re-dosing instructions, and requirement for blood glucose testing prior to medication delivery. Blood glucose testing prior to benzodiazepine administration is required by 61% (20/33) of agencies for adult patients and 76% (25/33) for pediatric patients. All agencies have protocols for giving intramuscular benzodiazepines and 76% (25/33) have protocols for intranasal benzodiazepines. Intramuscular midazolam dosages ranged from 2 to 10 mg per single adult dose, 2 to 8 mg per single pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intranasal midazolam dosages ranged from 2 to 10 mg per single adult or pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intravenous/intrasosseous midazolam dosages ranged from 1 to 6 mg per single adult dose, 1 to 5 mg per single pediatric dose, and 0.05 to 0.1 mg/kg as a weight-based dose. Eclampsia is specifically addressed by 85% (28/33) of agencies. Forty-two percent (14/33) have a protocol for administering magnesium sulfate, with intravenous dosages ranging from 2 to 6 mg, and 58% (19/33) allow benzodiazepines to be administered. Protocols for a patient with a seizure, including eclampsia and febrile seizures, vary widely across California. These recommendations for the prehospital diagnosis and treatment of seizures may be useful for EMS medical directors tasked with creating and revising these protocols.

Skin Dosimetry in Breast Teletherapy on a Phantom Anthropomorphic and Anthropometric Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batista Nogueira, Luciana; Lemos Silva, Hugo Leonardo; Donato da Silva, Sabrina

This paper addresses the breast teletherapy dosimetry. The goal is to evaluate and compare absorbed doses in equivalent skin tissue, TE-skin, of an anthropomorphic and anthropometric breast phantom submitted to breast radiotherapy. The methodology involved the reproduction of a set of tomographic images of the phantom; the elaboration of conformational radiotherapy planning in the SOMAVISION and CadPlan (TPS) software; and the synthetic breast irradiation by parallel opposed fields in 3D conformal teletherapy at 6 MV linear accelerator Clinac-2100 C from VARIAN with prescribed dose (PD) of 180 cGy to the target volume (PTV), referent to the glandular tissue. Radiochromic filmsmore » EBT2 were selected as dosimeters. Two independent calibration processes of films with solid water Gammex 457 plates and water filled box were produced. Curves of optical density (OD) versus absorbed dose were produced. Dosimeters were positioned in the external region of the breast phantom in contact with TE-skin, area of 4.0 cm{sup 2} each. The irradiation process was prepared in duplicate to check the reproducibility of the technique. The radiochromic films were scanned and their response in RGB (Red, Green, Blue) analyzed by the ImageJ software. The optical density was obtained and converted to dose based on the calibration curves. Thus, the spatial dose distribution in the skin was reproduced. The absorbed doses measured on the radiochromic films in TE-skin showed values between upper and lower quadrants at 9 o'clock in the range of 54% of PD, between the upper and lower quadrants 3 o'clock in the range of 72% and 6 o'clock at the lower quadrant in the range of 68 % of PD. The values are ±64% (p <0.05) according to the TPS. It is concluded that the depth dose measured in solid water plates or water box reproduce equivalent dose values for both calibration processes of the radiochromic films. It was observed that the skin received doses ranging from 50% to 78% of the prescribed dose after two parallel opposed irradiation fields. (authors)« less

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, B.; Huang, R.; Kuang, A.

2011-10-15

Purpose: The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ({sup 131}I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of {sup 131}I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Methods: Seventy-eight consecutive DTC patients (mean age 45 {+-} 17 years, 60%, female) undergoing {sup 131}I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of {sup 131}I to assess kinetics in themore » salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. Results: The maximum uptakes in percentage of administered {sup 131}I activity per kilogram of gland tissue (%/kg) were 12.9% {+-} 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% {+-} 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of {sup 131}I in the parotid and submandibular glands were 9.3 {+-} 3.5 h (range, 1.5-19.8 h) and 8.6 {+-} 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 {+-} 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 {+-} 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose contribution. Photon-absorbed dose fractions of total absorbed dose were 4.9% {+-} 1.3% (range, 1.1%-8.7%) and 3.7% {+-} 2.5% (range, 0.8%-7.9%) for the parotid and submandibular glands, respectively. Conclusions: The iodine uptake of salivary glands is continuously reduced during the courses of therapy. The phenomenon of hyper-radiosensitivity may to some extent account for the occurrence of salivary gland hypofunction at very low radiation doses with low dose rates in {sup 131}I therapy. On the other hand, failure to incorporate a nonuniform and preferential uptake by salivary gland ductal cells may result in underestimating the actual dose for the critical tissue. Other methods, including {sup 124}I voxel-based dosimetry, are warranted to further investigate the {sup 131}I-induced salivary gland toxicity.« less

Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia.

PubMed

Jakubowski, Joseph A; Hoppe, Carolyn C; Zhou, Chunmei; Smith, Brendan E; Brown, Patricia B; Heath, Lori E; Inusa, Baba; Rees, David C; Small, David S; Gupta, Neehar; Yao, Suqin; Heeney, Matthew; Kanter, Julie

2017-02-28

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients' P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12 ® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136-231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136-231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8  ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

Dose uniformity of budesonide Easyhaler® under simulated real-life conditions and with low inspiration flow rates.

PubMed

Haikarainen, Jussi; Rytilä, Paula; Roos, Sirkku; Metsärinne, Sirpa; Happonen, Anita

2017-01-01

Budesonide Easyhaler® multidose dry powder inhaler is approved for the treatment of asthma. Objectives were to determine the delivered dose (DD) uniformity of budesonide Easyhaler® in simulated real-world conditions and with different inspiration flow rates (IFRs). Three dose delivery studies were performed using 100, 200, and 400 µg/dose strengths of budesonide. Dose uniformity was assessed during in-use periods of 4-6 months after exposure to high temperature (30°C) and humidity (60% relative humidity) and after dropping and vibration testing. The influence of various IFRs (31, 43, and 54 L/min) on the DD was also investigated. Acceptable dose uniformity was declared when mean DD were within 80-120% of expected dose; all data reported descriptively. DD was constant (range: 93-109% of expected dose) at all in-use periods and after exposure to high temperature and humidity for a duration of up to 6 months. DD post-dropping and -vibration were unaffected (range 98-105% of expected dose). Similarly, DD was constant and within 10% of expected dose across all IFRs. Results indicate that budesonide Easyhaler® delivers consistently accurate doses in various real-life conditions. Budesonide Easyhaler® can be expected to consistently deliver a uniform dose and improve asthma control regardless of high temperature and humidity or varying IFR.

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

Dosimetric evaluation of the OneDoseTM MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures.

PubMed

Ding, George X; Coffey, Charles W

2010-09-01

The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, B; Brady, S; Kaufman, R

Purpose: Investigate the correlation of SSDE with organ dose in a pediatric population. Methods: Four anthropomorphic phantoms, representing a range of pediatric body habitus, were scanned with MOSFET dosimeters placed at 23 organ locations to determine absolute organ dosimetry. Phantom organ dosimetry was divided by phantom SSDE to determine correlation between organ dose and SSDE. Correlation factors were then multiplied by patient SSDE to estimate patient organ dose. Patient demographics consisted of 352 chest and 241 abdominopelvic CT examinations, 22 ± 15 kg (range 5−55 kg) mean weight, and 6 ± 5 years (range 4 mon to 23 years) meanmore » age. Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm. 23 organ correlation factors were determined in the chest and abdominopelvic region across nine pediatric weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7−1.4) and abdominopelvic (average 0.9; range 0.7−1.3) was near unity. For organs that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1−0.4) for both the chest and abdominopelvic regions, respectively. Pediatric organ dosimetry was compared to published values and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusion: Average correlation of SSDE and organ dosimetry was found to be better than ± 10% for fully covered organs within the scan volume. This study provides a list of organ dose correlation factors for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE.« less

Evaluation of various approaches for assessing dose indicators and patient organ doses resulting from radiotherapy cone-beam CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rampado, Osvaldo, E-mail: orampado@cittadellasalute.to.it; Giglioli, Francesca Romana; Rossetti, Veronica

Purpose: The aim of this study was to evaluate various approaches for assessing patient organ doses resulting from radiotherapy cone-beam CT (CBCT), by the use of thermoluminescent dosimeter (TLD) measurements in anthropomorphic phantoms, a Monte Carlo based dose calculation software, and different dose indicators as presently defined. Methods: Dose evaluations were performed on a CBCT Elekta XVI (Elekta, Crawley, UK) for different protocols and anatomical regions. The first part of the study focuses on using PCXMC software (PCXMC 2.0, STUK, Helsinki, Finland) for calculating organ doses, adapting the input parameters to simulate the exposure geometry, and beam dose distribution inmore » an appropriate way. The calculated doses were compared to readouts of TLDs placed in an anthropomorphic Rando phantom. After this validation, the software was used for analyzing organ dose variability associated with patients’ differences in size and gender. At the same time, various dose indicators were evaluated: kerma area product (KAP), cumulative air-kerma at the isocenter (K{sub air}), cone-beam dose index, and central cumulative dose. The latter was evaluated in a single phantom and in a stack of three adjacent computed tomography dose index phantoms. Based on the different dose indicators, a set of coefficients was calculated to estimate organ doses for a range of patient morphologies, using their equivalent diameters. Results: Maximum organ doses were about 1 mGy for head and neck and 25 mGy for chest and pelvis protocols. The differences between PCXMC and TLDs doses were generally below 10% for organs within the field of view and approximately 15% for organs at the boundaries of the radiation beam. When considering patient size and gender variability, differences in organ doses up to 40% were observed especially in the pelvic region; for the organs in the thorax, the maximum differences ranged between 20% and 30%. Phantom dose indexes provided better correlation with organ doses than K{sub air} and KAP, with average ratios ranging between 0.9 and 1.1 and variations for different organs and protocols below 20%. The triple phantom setup allowed us to take into account scatter dose contributions, but nonetheless, the correlation with the evaluated organ doses was not improved with this method. Conclusions: The simulation of rotational geometry and of asymmetric beam distribution by means of PCXMC 2.0 enabled us to determine patient organ doses depending on weight, height and gender. Alternatively, the measurement of an in phantom dose indicator combined with proper correction coefficients can be a useful tool for a first dose estimation of in-field organs. The data and coefficients provided in this study can be applied to any patient undergoing a scan by an Elekta XVI equipment.« less

The dose-response of Harshaw TLD-700H.

PubMed

Velbeck, K J; Luo, L Z; Ramlo, M J; Rotunda, J E

2006-01-01

Harshaw TLD-700H (7LiF:Mg,Cu,P) was previously characterised for low- to high-dose ranges from 1 microGy to 20 Gy. This paper describes the studies and results of dose-response and linearity at much higher doses. TLD-700H is a near perfect dosimetric material with near tissue equivalence, flat energy response, and the ability to measure beta, gamma and X rays. These new results extend the applicability of Harshaw TLD-700H into more dosimetric measurement environments. The simple glow curve structure provides insignificant fade, eliminating special oven preparation methods experienced by other materials. The work presented in this paper quantifies the performance of Harshaw TLD-700H in extended ranges.

Dosimetric characterization of a single crystal diamond detector in X-ray beams for preclinical research.

PubMed

Kampfer, Severin; Cho, Nathan; Combs, Stephanie E; Wilkens, Jan J

2018-05-29

The aim of this study was to investigate a single crystal diamond detector, the microDiamond detector from PTW (PTW-Freiburg, Freiburg, Germany), concerning the particular requirements in the set-up and energy range used in small animal radiotherapy (RT) research (around 220kV). We tested it to find out the minimal required pre-irradiation dose, the dose linearity, dose rate dependency and the angular response as well as usability in the small animal radiation research platform, SARRP (Xstrahl Ltd., Camberley, UK). For a stable signal in the range of energies used in the study, we found a required pre-irradiation dose of 10Gy. The dose linearity and dose rate dependence measurements showed a very good performance of the microDiamond detector. Regarding the effect of angular dependency, the variation of the response signal is less than 0.5% within the first 15° of the polar angle. In the azimuthal angle, however, there are differences in detector response up to 20%, depending on the range of energies used in the study. In addition, we compared the detector to a radiosensitive film for a profile measurement of a 5×5mm 2 irradiation field. Both methods showed a good accordance with the field size, however, the film has a steeper dose gradient in the penumbra region but also a higher noise than the microDiamond detector. We demonstrated that the microDiamond detector is a useful measurement tool for small animal RT research due to its small size. Nevertheless, it seems to be very important to verify the response of the detector in the given set-up and energy range. Copyright © 2018. Published by Elsevier GmbH.

Gentamicin ototoxicity: a 23-year selected case series of 103 patients.

PubMed

Ahmed, Rebekah M; Hannigan, Imelda P; MacDougall, Hamish G; Chan, Raymond C; Halmagyi, G Michael

2012-06-18

To review patients with severe bilateral vestibular loss associated with gentamicin treatment in hospital. A retrospective case series of presentations to a balance disorders clinic between 1988 and 2010. Relationship between vestibulotoxicity and gentamicin dose or dosing profile; indications for prescribing gentamicin. 103 patients (age, 18-84 years; mean, 64 years) presented with imbalance, oscillopsia or both, but none had vertigo. Only three noted some hearing impairment after having gentamicin, but audiometric thresholds for all patients were consistent with their age. In all patients, the following tests gave positive results: a bilateral clinical head-impulse test, a vertical head-shaking test for vertical oscillopsia, and a foam Romberg test. In 21 patients, imbalance occurred during gentamicin treatment (ignored or dismissed by prescribers in 20) and in 66 after treatment; the remaining 16 could not recall when symptoms were first noticed, except that it was after gentamicin treatment in hospital. Total gentamicin dose range was 2-318 mg/kg (mean, 52 mg/kg), daily dose range was 1.5-5.6 mg/kg (mean, 3.5mg/kg), and duration was 1-80 days (mean, 17 days). Six patients had only a single dose; 26 had five or fewer doses. Serum gentamicin levels, measured in 82 patients, were in the recommended range in 59. Time to diagnosis ranged from 4 days to 15 years. Nephrotoxicity developed in 43 patients. Gentamicin dosage complied with contemporary or current Australian antibiotic guidelines in under half the patients. Gentamicin ototoxicity is vestibular, not cochlear, producing permanent loss of balance, but not of hearing. Gentamicin can be vestibulotoxic in any dose, in any regimen, at any serum level.

SU-E-T-129: Dosimetric Evaluation of the Impact of Density Correction On Dose Calculation of Breast Cancer Treatment: A Study Based On RTOG 1005 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J; Yu, Y

Purpose: RTOG 1005 requires density correction in the dose calculation of breast cancer radiation treatment. The aim of the study was to evaluate the impact of density correction on the dose calculation. Methods: Eight cases were studied, which were planned on an XiO treatment planning system with pixel-by-pixel density correction using a superposition algorithm, following RTOG 1005 protocol requirements. Four were protocol Arm 1 (standard whole breast irradiation with sequential boost) cases and four were Arm 2 (hypofractionated whole breast irradiation with concurrent boost) cases. The plans were recalculated with the same monitor units without density correction. Dose calculations withmore » and without density correction were compared. Results: Results of Arm 1 and Arm 2 cases showed similar trends in the comparison. The average differences between the calculations with and without density correction (difference = Without - With) among all the cases were: -0.82 Gy (range: -2.65∼−0.18 Gy) in breast PTV Eval D95, −0.75 Gy (range: −1.23∼0.26 Gy) in breast PTV Eval D90, −1.00 Gy (range: −2.46∼−0.29 Gy) in lumpectomy PTV Eval D95, −0.78 Gy (range: −1.30∼0.11 Gy) in lumpectomy PTV Eval D90, −0.43% (range: −0.95∼−0.14%) in ipsilateral lung V20, −0.81% (range: −1.62∼−0.26%) in V16, −1.95% (range: −4.13∼−0.84%) in V10, −2.64% (−5.55∼−1.04%) in V8, −4.19% (range: −6.92∼−1.81%) in V5, and −4.95% (range: −7.49∼−2.01%) in V4, respectively. The differences in other normal tissues were minimal. Conclusion: The effect of density correction was observed in breast target doses (an average increase of ∼1 Gy in D95 and D90, compared to the calculation without density correction) and exposed ipsilateral lung volumes in low dose region (average increases of ∼4% and ∼5% in V5 and V4, respectively)« less

Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children.

PubMed

Englund, Janet A; Karron, Ruth A; Cunningham, Coleen K; Larussa, Philip; Melvin, Ann; Yogev, Ram; Handelsman, Ed; Siberry, George K; Thumar, Bhavanji; Schappell, Elizabeth; Bull, Catherine V; Chu, Helen Y; Schaap-Nutt, Anne; Buchholz, Ursula; Collins, Peter L; Schmidt, Alexander C

2013-11-19

Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

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

EPA Science Inventory

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

Cumulative doses analysis in young trauma patients: a single-centre experience.

PubMed

Salerno, Sergio; Marrale, Maurizio; Geraci, Claudia; Caruso, Giuseppe; Lo Re, Giuseppe; Lo Casto, Antonio; Midiri, Massimo

2016-02-01

Multidetector computed tomography (MDCT) represents the main source of radiation exposure in trauma patients. The radiation exposure of young patients is a matter of considerable medical concern due to possible long-term effects. Multiple MDCT studies have been observed in the young trauma population with an increase in radiation exposure. We have identified 249 young adult patients (178 men and 71 women; age range 14-40 years) who had received more than one MDCT study between June 2010 and June 2014. According to the International Commission on Radiological Protection publication, we have calculated the cumulative organ dose tissue-weighting factors by using CT-EXPO software(®). We have observed a mean cumulative dose of about 27 mSv (range from 3 to 297 mSv). The distribution analysis is characterised by low effective dose, below 20 mSv, in the majority of the patients. However, in 29 patients, the effective dose was found to be higher than 20 mSv. Dose distribution for the various organs analysed (breasts, ovaries, testicles, heart and eye lenses) shows an intense peak for lower doses, but in some cases high doses were recorded. Even though cumulative doses may have long-term effects, which are still under debate, high doses are observed in this specific group of young patients.

Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.

PubMed

Sarashina, Akiko; Koiwai, Kazuki; Seman, Leo J; Yamamura, Norio; Taniguchi, Atsushi; Negishi, Takahiro; Sesoko, Shogo; Woerle, Hans J; Dugi, Klaus A

2013-01-01

This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Samantha, E-mail: samantha.warren@oncology.ox.ac.uk; Partridge, Mike; Bolsi, Alessandra

Purpose: Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods andmore » Materials: For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV){sub 50Gy} or PTV{sub 62.5Gy} (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results: SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D{sub 98} was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D{sub 98} was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D{sub 98} was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D{sub 98} was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions: The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial.« less

Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

PubMed Central

Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

2017-01-01

After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and temporal effects on reducing individual external doses. PMID:28235009

An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning

PubMed Central

Warren, Samantha; Partridge, Mike; Bolsi, Alessandra; Lomax, Anthony J.; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

2016-01-01

Purpose Planning studies to compare x-ray and proton techniques and to select the most suitable technique for each patient have been hampered by the nonequivalence of several aspects of treatment planning and delivery. A fair comparison should compare similarly advanced delivery techniques from current clinical practice and also assess the robustness of each technique. The present study therefore compared volumetric modulated arc therapy (VMAT) and single-field optimization (SFO) spot scanning proton therapy plans created using a simultaneous integrated boost (SIB) for dose escalation in midesophageal cancer and analyzed the effect of setup and range uncertainties on these plans. Methods and Materials For 21 patients, SIB plans with a physical dose prescription of 2 Gy or 2.5 Gy/fraction in 25 fractions to planning target volume (PTV)50Gy or PTV62.5Gy (primary tumor with 0.5 cm margins) were created and evaluated for robustness to random setup errors and proton range errors. Dose–volume metrics were compared for the optimal and uncertainty plans, with P<.05 (Wilcoxon) considered significant. Results SFO reduced the mean lung dose by 51.4% (range 35.1%-76.1%) and the mean heart dose by 40.9% (range 15.0%-57.4%) compared with VMAT. Proton plan robustness to a 3.5% range error was acceptable. For all patients, the clinical target volume D98 was 95.0% to 100.4% of the prescribed dose and gross tumor volume (GTV) D98 was 98.8% to 101%. Setup error robustness was patient anatomy dependent, and the potential minimum dose per fraction was always lower with SFO than with VMAT. The clinical target volume D98 was lower by 0.6% to 7.8% of the prescribed dose, and the GTV D98 was lower by 0.3% to 2.2% of the prescribed GTV dose. Conclusions The SFO plans achieved significant sparing of normal tissue compared with the VMAT plans for midesophageal cancer. The target dose coverage in the SIB proton plans was less robust to random setup errors and might be unacceptable for certain patients. Robust optimization to ensure adequate target coverage of SIB proton plans might be beneficial. PMID:27084641

Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

PubMed Central

Booth, J. C.; Rweyemamu, M. M.; Pay, T. W.

1978-01-01

Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection. PMID:202650

Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure to inorganic arsenic.

PubMed

Gentry, P R; Yager, J W; Clewell, R A; Clewell, H J

2014-10-01

In the recent National Research Council report on conducting a dose-response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose-response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose-response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose-response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations <100 ppb in epidemiological studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Monte Carlo proton dose calculations using a radiotherapy specific dual-energy CT scanner for tissue segmentation and range assessment

NASA Astrophysics Data System (ADS)

Almeida, Isabel P.; Schyns, Lotte E. J. R.; Vaniqui, Ana; van der Heyden, Brent; Dedes, George; Resch, Andreas F.; Kamp, Florian; Zindler, Jaap D.; Parodi, Katia; Landry, Guillaume; Verhaegen, Frank

2018-06-01

Proton beam ranges derived from dual-energy computed tomography (DECT) images from a dual-spiral radiotherapy (RT)-specific CT scanner were assessed using Monte Carlo (MC) dose calculations. Images from a dual-source and a twin-beam DECT scanner were also used to establish a comparison to the RT-specific scanner. Proton ranges extracted from conventional single-energy CT (SECT) were additionally performed to benchmark against literature values. Using two phantoms, a DECT methodology was tested as input for GEANT4 MC proton dose calculations. Proton ranges were calculated for different mono-energetic proton beams irradiating both phantoms; the results were compared to the ground truth based on the phantom compositions. The same methodology was applied in a head-and-neck cancer patient using both SECT and dual-spiral DECT scans from the RT-specific scanner. A pencil-beam-scanning plan was designed, which was subsequently optimized by MC dose calculations, and differences in proton range for the different image-based simulations were assessed. For phantoms, the DECT method yielded overall better material segmentation with  >86% of the voxel correctly assigned for the dual-spiral and dual-source scanners, but only 64% for a twin-beam scanner. For the calibration phantom, the dual-spiral scanner yielded range errors below 1.2 mm (0.6% of range), like the errors yielded by the dual-source scanner (<1.1 mm, <0.5%). With the validation phantom, the dual-spiral scanner yielded errors below 0.8 mm (0.9%), whereas SECT yielded errors up to 1.6 mm (2%). For the patient case, where the absolute truth was missing, proton range differences between DECT and SECT were on average in  ‑1.2  ±  1.2 mm (‑0.5%  ±  0.5%). MC dose calculations were successfully performed on DECT images, where the dual-spiral scanner resulted in media segmentation and range accuracy as good as the dual-source CT. In the patient, the various methods showed relevant range differences.

Effect of chronic kidney disease on warfarin management in a pharmacist-managed anticoagulation clinic.

PubMed

Kleinow, Megan E; Garwood, Candice L; Clemente, Jennifer L; Whittaker, Peter

2011-09-01

There is growing evidence that kidney disease affects hepatically cleared drugs. Accordingly, we hypothesized that chronic kidney disease (CKD) would disrupt anticoagulation of warfarin-treated patients and thereby increase the amount of management required to maintain appropriate anticoagulation. Specifically, we anticipated that more dose manipulations (both dose changes and transient dose adjustments) and shorter times between scheduled clinic visits would be required for anticoagulation patients with CKD. To determine how CKD affected warfarin maintenance dose, anticoagulation stability, the proportion of clinic visits that necessitated a dose manipulation (either a change in the prescribed weekly dose or a transient dose adjustment), and the length of time between scheduled visits in 2 pharmacist-managed anticoagulation clinics. Our retrospective, cohort chart review investigated warfarin response in anticoagulation clinic patients. From the clinic database of patients with an international normalized ratio (INR) target range of 2.0-3.0, we matched 20 of 24 patients with CKD (estimated creatinine clearance less than 60 mL per minute) to 20 comparison group patients (estimated creatinine clearance greater than 60 mL per minute) based on parameters demonstrated to affect warfarin dose: ethnicity, gender, age, body surface area, and simvastatin use. We calculated the average weekly dose used to maintain target INR (assessment period range=116-1,408 days). To evaluate anticoagulation stability and patient management, we quantified several parameters, including the percentage of total time in therapeutic range, the proportion of clinic visits that required a dose change, and the time between scheduled visits. We compared group means using t-tests, and categorical data were compared using Fisher's exact test. Our population was predominantly female (75%) and of African ancestry (95%); average age 60 years. Patients with CKD required a 24% lower dose than the comparison group (mean [SD]=35.9 [10.7] vs. 47.0 [11.2] mg per week, P=0.003) and spent less time in therapeutic range required increased clinic management versus the comparison group, as indicated by a significantly higher proportion of clinic visits at which dose changes occurred (22% vs. 12%, P<0.001) and a decreased time between scheduled visits (mean [SD] of 16.0 [3.2] days vs. 19.7 [3.4] days, respectively, P=0.001). CKD was associated with both decreased warfarin maintenance dose and decreased anticoagulation stability which, in turn, required more frequent and intensive anticoagulation clinic management.

Very low dose gamma irradiation stimulates gaseous exchange and carboxylation efficiency, but inhibits vascular sap flow in groundnut (Arachis hypogaea L.).

PubMed

Ahuja, Sumedha; Singh, Bhupinder; Gupta, Vijay Kumar; Singhal, R K; Venu Babu, P

2014-02-01

An experiment was carried out to determine the effect of low dose gamma radiation on germination, plant growth, nitrogen and carbon fixation and carbon flow and release characteristics of groundnut. Dry seeds of groundnut variety Trombay groundnut 37A (TG 37A), a radio mutant type developed by Bhabha Atomic Research Centre (BARC), Mumbai, India, were subjected to the pre-sowing treatment of gamma radiation within low to high dose physiological range, i.e., 0.0, 0.0082, 0.0164. 0.0328, 0.0656, 0.1312, 5, 25, 100, 500 Gray (Gy) from a cobalt source ((60)Co). Observations were recorded for the radiation effect on percentage germination, vigour, gas exchange attributes such as photosynthetic rate, stomatal conductance and transpiration rate, chlorophyll content, root exudation in terms of (14)C release, vascular sap flow rate and activities of rate defining carbon and nitrogen assimilating enzymes such as ribulose-1,5-bisphosphate carboxylase (rubisco) and nitrate reductase (NR). Seed germination was increased by 10-25% at the lower doses up to 5 Gy while the improvement in plant vigour in the same dose range was much higher (22-84%) than the unirradiated control. For radiation exposure above 5 Gy, a dose-dependent decline in germination and plant vigour was measured. No significant effect was observed on the photosynthesis at radiation exposure below 5 Gy but above 5 Gy dose there was a decline in the photosynthetic rate. Stomatal conductance and transpiration rate, however, were only inhibited at a high dose of 500 Gy. Leaf rubisco activity and NR activities remained unaffected at all the investigated doses of gamma irradiation. Mean root exudation and sap flow rate of the irradiated plants, irrespective of the dose, was reduced over the unirradiated control more so in a dose-dependent manner. Results indicated that a very low dose of gamma radiation, in centigray to gray range, did not pose any threat and in fact stimulated metabolic functions in such a way to aid growth and development of groundnut plants. It further showed that the radiation threshold for the gas exchange traits and rubisco activity, which ultimately determine the plant health and yield, were higher than compared to the other metabolic attributes and were well beyond 500 Gy and that the dose range above 500 Gy should be targeted to measure lethal effects of radiation on carbon assimilation attributes in leguminous crops, in general, and groundnut in particular.

Pharmacokinetics and clinical application of intravenous valproate in Thai epileptic children.

PubMed

Visudtibhan, Anannit; Bhudhisawadi, Kasama; Vaewpanich, Jarin; Chulavatnatol, Suvatna; Kaojareon, Sming

2011-03-01

Roles of intravenous administration of valproate in status epilepticus and serial seizures are documented in adults and children. Pharmacokinetic parameters are necessary to predict the optimum therapeutic level after administration. A cross-sectional study to determine the pharmacokinetic parameters and safety of intravenous valproate for future application was conducted in Thai children from January to December 2008. There were eleven children, age-range 1-15 years (mean age 9.5 years) enrolled. Valproate of 15-20 mg/kg was administrated intravenously at the rate of 3 mg/kg/min, followed by 6 mg/kg every 6 h. Valproate level was determined prior to the initial dose and at ½, 1, 2, 4, 5, and 6 h postdose. Complete blood count, serum ammonia, and liver function tests were collected prior to the initial dose and at 6 h. Median loading dose was 19 mg/kg (range 15-20.5 mg/kg). Median maximum concentration at 30 min after infusion was 98.8 mcg/mL (range 67-161 mcg/mL). Median volume of distribution was 0.20 L/kg (range 0.15-0.53 L/kg). Median half-life was 9.5 h (range 4.4-24.2 h). Median clearance was 0.02 L/h/kg (range 0.01-0.05 L/h/kg). Six hours after initial dose, eight children did not have recurrent seizure. One child had brief seizure at 20 min after initial dose. Seizure recurred in two children at 4th and 5th hour. Asymptomatic transient elevation of serum ammonia was observed in two children. Volume of distribution of 0.20 L/kg could be applied for initial intravenous administration with a favorable efficacy. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The space radiation environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, D E

There are three primary sources of space radiation: galactic cosmic rays (GCR), trapped belt radiation, and solar particle events (SPE). All are composed of ions, the nuclei of atoms. Their energies range from a few MeV u{sup -1} to over a GeV u{sup -1}. These ions can fragment when they interact with spacecraft materials and produce energetic neutrons and ions of lower atomic mass. Absorbed dose rates inside a typical spacecraft (like the Space Shuttle) in a low inclination (28.5 degrees) orbit range between 0.05 and 2 mGy d{sup -1} depending on the altitude and flight inclination (angle of orbitmore » with the equator). The quality factor of radiation in orbit depends on the relative contributions of trapped belt radiation and GCR, and the dose rate varies both with orbital altitude and inclination. The corresponding equivalent dose rate ranges between 0.1 and 4 mSv d{sup -1}. In high inclination orbits, like that of the Mir Space Station and as is planned for the International Space Station, blood-forming organ (BFO) equivalent dose rates as high as 1.5 mSv d{sup -1}. Thus, on a 1 y mission, a crew member could obtain a total dose of 0.55 Sv. Maximum equivalent dose rates measured in high altitude passes through the South Atlantic Anomaly (SAA) were 10 mSv h{sup -1}. For an interplanetary space mission (e.g., to Mars) annual doses from GCR alone range between 150 mSv y{sup -1} at solar maximum and 580 mSv y{sup -1} at solar minimum. Large SPE, like the October 1989 series, are more apt to occur in the years around solar maximum. In free space, such an event could contribute another 300 mSv, assuming that a warning system and safe haven can be effectively used with operational procedures to minimize crew exposures. Thus, the total dose for a 3 y mission to Mars could exceed 2 Sv.« less

The incidence of the different sources of noise on the uncertainty in radiochromic film dosimetry using single channel and multichannel methods

NASA Astrophysics Data System (ADS)

González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

2017-11-01

The influence of the various sources of noise on the uncertainty in radiochromic film (RCF) dosimetry using single channel and multichannel methods is investigated in this work. These sources of noise are extracted from pixel value (PV) readings and dose maps. Pieces of an RCF were each irradiated to different uniform doses, ranging from 0 to 1092 cGy. Then, the pieces were read at two resolutions (72 and 150 ppp) with two flatbed scanners: Epson 10000XL and Epson V800, representing two states of technology. Noise was extracted as described in ISO 15739 (2013), separating its distinct constituents: random noise and fixed pattern (FP) noise. Regarding the PV maps, FP noise is the main source of noise for both models of digitizer. Also, the standard deviation of the random noise in the 10000XL model is almost twice that of the V800 model. In the dose maps, the FP noise is smaller in the multichannel method than in the single channel ones. However, random noise is higher in this method, throughout the dose range. In the multichannel method, FP noise is reduced, as a consequence of this method’s ability to eliminate channel independent perturbations. However, the random noise increases, because the dose is calculated as a linear combination of the doses obtained by the single channel methods. The values of the coefficients of this linear combination are obtained in the present study, and the root of the sum of their squares is shown to range between 0.9 and 1.9 over the dose range studied. These results indicate the random noise to play a fundamental role in the uncertainty of RCF dosimetry: low levels of random noise are required in the digitizer to fully exploit the advantages of the multichannel dosimetry method. This is particularly important for measuring high doses at high spatial resolutions.

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

PubMed

von Tresckow, Bastian; Morschhauser, Franck; Ribrag, Vincent; Topp, Max S; Chien, Caly; Seetharam, Shobha; Aquino, Regina; Kotoulek, Sonja; de Boer, Carla J; Engert, Andreas

2015-04-15

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL). Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics. Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing). JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL. ©2015 American Association for Cancer Research.

Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial.

PubMed

Singer, Daniel E; Hellkamp, Anne S; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R; Piccini, Jonathan P; Hankey, Graeme J; Breithardt, Günter; Halperin, Jonathan L; Becker, Richard C; Hacke, Werner; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

2015-03-03

In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted. TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported. URL: ClinicalTrials.gov. Unique identifier: NCT00403767. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

PubMed Central

Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

2015-01-01

Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

Intraarticular Sacroiliac Joint Injection Under Computed Tomography Fluoroscopic Guidance: A Technical Note to Reduce Procedural Time and Radiation Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paik, Nam Chull, E-mail: pncspine@gmail.com

2016-07-15

PurposeA technique for computed tomography fluoroscopy (CTF)-guided intraarticular (IA) sacroiliac joint (SIJ) injection was devised to limit procedural time and radiation dose.MethodsOur Institutional Review Board approved this retrospective analysis and waived the requirement for informed consent. Overall, 36 consecutive diagnostic or therapeutic IA SIJ injections (unilateral, 20; bilateral, 16) performed in 34 patients (female, 18; male, 16) with a mean age of 45.5 years (range 20–76 years) under CTF guidance were analyzed, assessing technical success (i.e., IA contrast spread), procedural time, and radiation dose.ResultsAll injections were successful from a technical perspective and were free of serious complications. Respective median proceduralmore » times and effective doses of SIJ injection were as follows: unilateral, 5.28 min (range 3.58–8.00 min) and 0.11 millisievert (mSv; range 0.07–0.24 mSv); and bilateral, 6.72 min (range 4.17–21.17 min) and 0.11 mSv (range 0.09–0.51 mSv).ConclusionsGiven the high rate of technical success achieved in limited time duration and with little radiation exposure, CTF-guided IA SIJ injection is a practical and low-risk procedure.« less

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances.

PubMed

Orito, Kensuke; Kawarai-Shimamura, Asako; Ogawa, Atsushi; Nakamura, Atsushi

2017-12-22

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20-50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25-50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26-370 sec), median duration of emesis was 151.5 sec (range, 30-780 sec), and median number of emesis episodes was 2 (range, 1-8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting.

SU-F-T-322: A Comparison of Two Si Detectors for in Vivo Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talarico, O; Krylova, T; Lebedenko, I

Purpose: To compare two types of semiconductor detectors for in vivo dosimetry by their dependence from various parameters in different conditions. Methods: QED yellow (Sun Nuclear) and EDP (Scanditronix) Si detectors were radiated by a Varian Clinac 2300 ix with 6 and 18 MV energies. 10 cm thickness water equivalent phantom consisted of 30×30 cm{sup 2} squared plates was used for experiments. Dose dependencies for different beam angles (0 – 180°), field size (3–40 cm), dose (50 – 300 MU), and dose rates (50 – 300 MU/min) were obtained and calibrated with Standard Farmer chamber (PTW). Results: Reproducibility, linearity, dosemore » rate, angular dependence, and field size dependence were obtained for QED and EDP. They show no dose-rate dependence in available clinical dose rate range (100–600 MU/min). Both diodes have linear dependence with increasing the dose. Therefore even in case of high radiation therapy (including total body irradiation) it is not necessary to apply an additional correction during in vivo dosimetry. The diodes have different behavior for angular and field size dependencies. QED diode showed that dose value is stable for beam angles from 0 to 60°, for 60–180° correction factor has to be applied for each beam angle during in vivo measurements. For EDP diode dose value is sensitive to beam angle in whole range of angles. Conclusion: The study shows that QED diode is more suitable for in vivo dosimetry due to dose value independence from incident beam angle in the range 0–60°. There is no need in correction factors for increasing of dose and dose rate for both diodes. The next step will be to carry out measurements in non-standard conditions of total body irradiation. After this modeling of these experiments with Monte Carlo simulation for comparison calculated and obtained data is planned.« less

SU-E-I-42: Normalized Embryo/fetus Doses for Fluoroscopically Guided Pacemaker Implantation Procedures Calculated Using a Monte Carlo Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Damilakis, J; Stratakis, J; Solomou, G

Purpose: It is well known that pacemaker implantation is sometimes needed in pregnant patients with symptomatic bradycardia. To our knowledge, there is no reported experience regarding radiation doses to the unborn child resulting from fluoroscopy during pacemaker implantation. The purpose of the current study was to develop a method for estimating embryo/fetus dose from fluoroscopically guided pacemaker implantation procedures performed on pregnant patients during all trimesters of gestation. Methods: The Monte Carlo N-Particle (MCNP) radiation transport code was employed in this study. Three mathematical anthropomorphic phantoms representing the average pregnant patient at the first, second and third trimesters of gestationmore » were generated using Bodybuilder software (White Rock science, White Rock, NM). The normalized embryo/fetus dose from the posteroanterior (PA), the 30° left-anterior oblique (LAO) and the 30° right-anterior oblique (RAO) projections were calculated for a wide range of kVp (50–120 kVp) and total filtration values (2.5–9.0 mm Al). Results: The results consist of radiation doses normalized to a) entrance skin dose (ESD) and b) dose area product (DAP) so that the dose to the unborn child from any fluoroscopic technique and x-ray device used can be calculated. ESD normalized doses ranged from 0.008 (PA, first trimester) to 2.519 μGy/mGy (RAO, third trimester). DAP normalized doses ranged from 0.051 (PA, first trimester) to 12.852 μGy/Gycm2 (RAO, third trimester). Conclusion: Embryo/fetus doses from fluoroscopically guided pacemaker implantation procedures performed on pregnant patients during all stages of gestation can be estimated using the method developed in this study. This study was supported by the Greek Ministry of Education and Religious Affairs, General Secretariat for Research and Technology, Operational Program ‘Education and Lifelong Learning’, ARISTIA (Research project: CONCERT)« less

Radiation-Induced Middle Ear and Mastoid Opacification in Skull Base Tumors Treated With Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, Gary V.; Ahmed, Salmaan; Allen, Pamela

Purpose: To assess the incidence of middle ear (ME) pathology in patients treated with radiotherapy (RT) for skull base tumors. Methods and Materials: A retrospective analysis of 61 patients treated with RT between 2003 and 2008 for skull base tumors was conducted. Clinical outcomes and demographics were reviewed. Dose-volume histogram analysis was performed on the eustachian canal (EC), ME, mastoid air cells, vestibular apparatus, cochlea, internal auditory canal, lateral and posterior nasopharynx, and temporal lobes to relate doses to symptoms and radiographic change. Otomastoid opacification was rated 0 (none), 1 (mild), 2 (moderate), and 3 (severe) by a neuroradiologist blindedmore » to clinical outcomes and doses. Results: The median prescribed dose was 50.4 Gy (range, 14-74 Gy). The ME mean dose was 14 Gy and 34 Gy for Grade 0-1 and 2-3 opacification, respectively (p < 0.0001). The mean mastoid dose was 10 Gy and 26 Gy for Grade 0-1 and 2-3, respectively (p < 0.0001). The mean EC dose was 17 Gy and 32 Gy for Grade 0-1 and 2-3, respectively (p = 0.0001). Otomastoid opacification resolved in 17 of 40 patients (42.5%), at a mean of 17 months after RT (range, 2-45 months). Otomastoid opacification persisted in 23 of 40 patients (57.5%), with a mean follow-up of 23 months (range, 2-55 months). Multivariate analysis showed that mastoid dose >30 Gy (odds ratio = 28.0, p < 0.001) and posterior nasopharynx dose of >30 Gy (odds ratio = 4.9, p = 0.009) were associated with Grade 2-3 effusions, whereas other factors including dose to EC and ME were not significant. Conclusions: A mean RT dose >30 Gy to the mastoid air cells or posterior nasopharynx is associated with increased risk of moderate to severe otomastoid opacification, which persisted in more than half of patients at 2-year follow-up.« less

SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bichay, T; Mayville, A

2016-06-15

Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fractionmore » and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.« less

SU-F-T-130: [18F]-FDG Uptake Dose Response in Lung Correlates Linearly with Proton Therapy Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, D; Titt, U; Mirkovic, D

2016-06-15

Purpose: Analysis of clinical outcomes in lung cancer patients treated with protons using 18F-FDG uptake in lung as a measure of dose response. Methods: A test case lung cancer patient was selected in an unbiased way. The test patient’s treatment planning and post treatment positron emission tomography (PET) were collected from picture archiving and communication system at the UT M.D. Anderson Cancer Center. Average computerized tomography scan was registered with post PET/CT through both rigid and deformable registrations for selected region of interest (ROI) via VelocityAI imaging informatics software. For the voxels in the ROI, a system that extracts themore » Standard Uptake Value (SUV) from PET was developed, and the corresponding relative biological effectiveness (RBE) weighted (both variable and constant) dose was computed using the Monte Carlo (MC) methods. The treatment planning system (TPS) dose was also obtained. Using histogram analysis, the voxel average normalized SUV vs. 3 different doses was obtained and linear regression fit was performed. Results: From the registration process, there were some regions that showed significant artifacts near the diaphragm and heart region, which yielded poor r-squared values when the linear regression fit was performed on normalized SUV vs. dose. Excluding these values, TPS fit yielded mean r-squared value of 0.79 (range 0.61–0.95), constant RBE fit yielded 0.79 (range 0.52–0.94), and variable RBE fit yielded 0.80 (range 0.52–0.94). Conclusion: A system that extracts SUV from PET to correlate between normalized SUV and various dose calculations was developed. A linear relation between normalized SUV and all three different doses was found.« less

SU-E-T-115: Dose Perturbation Study of Self-Expandable Metal and Polyester Esophageal Stents in Proton Therapy Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S; Li, Z; Jalaj, S

2014-06-01

Purpose: This work investigates dose perturbations due to Self-expandable metal and polyester esophageal stents undergoing proton radiotherapy for esophageal cancer. Methods: Five commercially available esophageal stents made of nitinol (Evolution, Wallflex and Ultraflex), stainless steel (Z-Stent) and polyester (Polyflex) were tested. Radiochromic film (GafChromic EBT3 film, Ashland, Covington, KY) wrapped around a stent and a 12cc syringe was irradiated with 2CGE (Cobalt Gray Equivalent) of proton beam in a custom fabricated acrylic phantom. An air-hollow syringe simulates the esophagus. Results: The Z-stent created the largest dose perturbations ranges from -14.5% to 6.1% due to the steel composition. The WallFlex, Evolutionmore » and Ultraflex stents produced the dose perturbation ranges of (−9.2%∼8.6%), (−6.8%∼5.7%) and (−6.2%∼6.2%), respectively. The PolyFlex stent contains the radiopaque tungsten markers located top, middle and bottom portions. When the focal cold spots induced by the markers were excluded in the analysis, the dose perturbation range was changed from (−11.6%∼6.4%) to (−0.6%∼5.0%). Conclusion: The magnitude of dose perturbation is related to material of a metallic stent. The non-metallic stent such as PolyFlex shows relatively lower dose perturbation than metallic stents except a radiopaque marker region. Overall Evolution and Ultraflex stent appear to be less dose perturbations. The largest dose perturbations (cold spots) were located at both edges of stents in distal area for the single proton beam irradiation study. The analysis of more than two proton beam which is more typical clinical beam arrangement would be necessary to minimize the doe perturbation effect in proton ratiotherapy.« less

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parsons, J.T.; Bova, F.J.; Million, R.R.

1994-11-15

To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 andmore » 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.« less

Overweight Kidney Transplant Recipients Are at Risk of Being Overdosed Following Standard Bodyweight-Based Tacrolimus Starting Dose

PubMed Central

Andrews, Louise M.; de Winter, Brenda C.M.; Tang, Jiang-Tao; Shuker, Nauras; Bouamar, Rachida; van Schaik, Ron H.N.; Koch, Birgit C.P.; van Gelder, Teun; Hesselink, Dennis A.

2017-01-01

Background Bodyweight-based dosing of tacrolimus (Tac) is considered standard care, even though the available evidence is thin. An increasing proportion of transplant recipients is overweight, prompting the question if the starting dose should always be based on bodyweight. Methods For this analysis, data were used from a randomized-controlled trial in which patients received either a standard Tac starting dose or a dose that was based on CYP3A5 genotype. The hypothesis was that overweight patients would have Tac overexposure following standard bodyweight-based dosing. Results Data were available for 203 kidney transplant recipients, with a median body mass index (BMI) of 25.6 (range, 17.2-42.2). More than 50% of the overweight or obese patients had a Tac predose concentration above the target range. The CYP3A5 nonexpressers tended to be above target when they weighed more than 67.5 kg or had a BMI of 24.5 or higher. Dosing guidelines were proposed with a decrease up to 40% in Tac starting doses for different BMI groups. The dosing guideline for patients with an unknown genotype was validated using the fixed-dose versus concentration controlled data set. Conclusions This study demonstrates that dosing Tac solely on bodyweight results in overexposure in more than half of overweight or obese patients. PMID:28361113

Digital radiography can reduce scoliosis x-ray exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kling, T.F. Jr.; Cohen, M.J.; Lindseth, R.E.

1990-09-01

Digital radiology is a new computerized system of acquiring x-rays in a digital (electronic) format. It possesses a greatly expanded dose response curve that allows a very broad range of x-ray dose to produce a diagnostic image. Potential advantages include significantly reduced radiation exposure without loss of image quality, acquisition of images of constant density irrespective of under or over exposure, and reduced repeat rates for unsatisfactory films. The authors prospectively studied 30 adolescents with scoliosis who had both conventional (full dose) and digital (full, one-half, or one-third dose) x-rays. They found digital made AP and lateral image with allmore » anatomic areas clearly depicted at full and one-half dose. Digital laterals were better at full dose and equal to conventional at one-half dose. Cobb angles were easily measured on all one-third dose AP and on 8 of 10 one-third dose digital laterals. Digital clearly depicted the Risser sign at one-half and one-third dose and the repeat rate was nil in this study, indicating digital compensates well for exposure errors. The study indicates that digital does allow radiation dose to be reduced by at least one-half in scoliosis patients and that it does have improved image quality with good contrast over a wide range of x-ray exposure.« less

Childhood mortality impact and costs of integrating vitamin A supplementation into immunization campaigns.

PubMed Central

Ching, P; Birmingham, M; Goodman, T; Sutter, R; Loevinsohn, B

2000-01-01

Country-specific activity and coverage data were used to estimate the childhood mortality impact (deaths averted) and costs of integrating vitamin A supplements into immunization campaigns conducted in 1998 and 1999. More than 94 million doses of vitamin A were administered in 41 countries in 1998, helping to avert nearly 169,000 deaths. During 1999, delivery of more than 97 million doses in 50 countries helped avert an estimated 242,000 deaths. The estimated incremental cost per death averted was US$72 (range: 36-142) in 1998 and US$64 (range: 32-126) in 1999. The estimated average total cost of providing supplementation per death averted was US$310 (range: 157-609) in 1998 and US$276 (range: 139-540) in 1999. Costs per death averted varied by campaign, depending on the number and proportion of the child population reached, number of doses received per child, and child mortality rates. PMID:11029982

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, R; Zhu, X; Li, S

Purpose: High Dose Rate (HDR) brachytherapy forward planning is principally an iterative process; hence, plan quality is affected by planners’ experiences and limited planning time. Thus, this may lead to sporadic errors and inconsistencies in planning. A statistical tool based on previous approved clinical treatment plans would help to maintain the consistency of planning quality and improve the efficiency of second checking. Methods: An independent dose calculation tool was developed from commercial software. Thirty-three previously approved cervical HDR plans with the same prescription dose (550cGy), applicator type, and treatment protocol were examined, and ICRU defined reference point doses (bladder, vaginalmore » mucosa, rectum, and points A/B) along with dwell times were collected. Dose calculation tool then calculated appropriate range with a 95% confidence interval for each parameter obtained, which would be used as the benchmark for evaluation of those parameters in future HDR treatment plans. Model quality was verified using five randomly selected approved plans from the same dataset. Results: Dose variations appears to be larger at the reference point of bladder and mucosa as compared with rectum. Most reference point doses from verification plans fell between the predicted range, except the doses of two points of rectum and two points of reference position A (owing to rectal anatomical variations & clinical adjustment in prescription points, respectively). Similar results were obtained for tandem and ring dwell times despite relatively larger uncertainties. Conclusion: This statistical tool provides an insight into clinically acceptable range of cervical HDR plans, which could be useful in plan checking and identifying potential planning errors, thus improving the consistency of plan quality.« less

Macacine Herpesvirus 1 in Long-Tailed Macaques, Malaysia, 2009–2011

PubMed Central

Lee, Mei-Ho; Rostal, Melinda K.; Hughes, Tom; Sitam, Frankie; Lee, Chee-Yen; Japning, Jeffrine; Harden, Mallory E.; Griffiths, Anthony; Basir, Misliah; Wolfe, Nathan D.; Daszak, Peter

2015-01-01

Macacine herpesvirus 1 (MaHV1; B virus) naturally infects macaques (Macaca spp.) and can cause fatal encephalitis in humans. In Peninsular Malaysia, wild macaques are abundant, and translocation is used to mitigate human–macaque conflict. Most adult macaques are infected with MaHV1, although the risk for transmission to persons who handle them during capture and translocation is unknown. We investigated MaHV1 shedding among 392 long-tailed macaques (M. fascicularis) after capture and translocation by the Department of Wildlife and National Parks in Peninsular Malaysia, during 2009–2011. For detection of MaHV1 DNA, PCR was performed on urogenital and oropharyngeal swab samples. Overall, 39% of macaques were shedding MaHV1 DNA; rates of DNA detection did not differ between sample types. This study demonstrates that MaHV1 was shed by a substantial proportion of macaques after capture and transport and suggests that persons handling macaques under these circumstances might be at risk for exposure to MaHV1. PMID:26080081

Local field potential spectral tuning in motor cortex during reaching.

PubMed

Heldman, Dustin A; Wang, Wei; Chan, Sherwin S; Moran, Daniel W

2006-06-01

In this paper, intracortical local field potentials (LFPs) and single units were recorded from the motor cortices of monkeys (Macaca fascicularis) while they preformed a standard three-dimensional (3-D) center-out reaching task. During the center-out task, the subjects held their hands at the location of a central target and then reached to one of eight peripheral targets forming the corners of a virtual cube. The spectral amplitudes of the recorded LFPs were calculated, with the high-frequency LFP (HF-LFP) defined as the average spectral amplitude change from baseline from 60 to 200 Hz. A 3-D linear regression across the eight center-out targets revealed that approximately 6% of the beta LFPs (18-26 Hz) and 18% of the HF-LFPs were tuned for velocity (p-value < 0.05), while 10% of the beta LFPs and 15% of the HF-LFPs were tuned for position. These results suggest that a multidegree-of-freedom brain-machine interface is possible using high-frequency LFP recordings in motor cortex.

Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer.

PubMed

Liu, Zhen; Cai, Yijun; Wang, Yan; Nie, Yanhong; Zhang, Chenchen; Xu, Yuting; Zhang, Xiaotong; Lu, Yong; Wang, Zhanyang; Poo, Muming; Sun, Qiang

2018-02-08

Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys (Macaca fascicularis) by somatic cell nuclear transfer (SCNT). We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys. For SCNT using fetal monkey fibroblasts, 6 pregnancies were confirmed in 21 surrogates and yielded 2 healthy babies. For SCNT using adult monkey cumulus cells, 22 pregnancies were confirmed in 42 surrogates and yielded 2 babies that were short-lived. In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts. Copyright © 2018 Elsevier Inc. All rights reserved.

The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

PubMed

Kanthaswamy, S; Ng, J; Satkoski Trask, J; George, D A; Kou, A J; Hoffman, L N; Doherty, T B; Houghton, P; Smith, D G

2013-06-01

The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

PubMed Central

Whitehouse, Chris A.; Chase, Kitty; Embers, Monica E.; Kulesh, David A.; Ladner, Jason T.; Palacios, Gustavo F.; Minogue, Timothy D.

2016-01-01

Background Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. Methods We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. Results All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. Conclusions We developed several accurate, sensitive, and species-specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID:26365904

Reduced Marker of Vascularization in the Anterior Hippocampus in a Female Monkey Model of Depression

PubMed Central

Kalidindi, Anisha; Kelly, Sean D.; Singleton, Kaela S.; Guzman, Dora; Merrill, Liana; Willard, Stephanie L.; Shively, Carol A.; Neigh, Gretchen N.

2016-01-01

Depression is a common and debilitating mood disorder that impacts women more often than men. The mechanisms that result in depressive behaviors are not fully understood; however, the hippocampus has been noted as a key structure in the pathophysiology of depression. In addition to neural implications of depression, the cardiovascular system is impacted. Although not as commonly considered, the cerebrovasculature is critical to brain function, impacted by environmental stimuli, and is capable of altering neural function and thereby behavior. In the current study, we assessed the relationship between depressive behavior and a marker of vascularization of the hippocampus in adult female cynomolgus macaques (Macaca fascicularis). Similar to previously noted impacts on neuropil and glia, the depressed phenotype predicts a reduction in a marker of vascular length in the anterior hippocampus. These data reinforce the growing recognition of the effects of depression on vasculature and support further consideration of vascular endpoints in studies aimed at the elucidation of the mechanisms underlying depression. PMID:27423324

Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

NASA Technical Reports Server (NTRS)

Hill, F. S.; Cox, A. B.; Salmon, Y. L.; Cantu, A. O.; Lucas, J. N.

1994-01-01

The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.

PubMed

Kavanagh, Kylie; Koudy Williams, J; Wagner, Janice D

2005-08-01

Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.

An enzootic outbreak of acute disease associated with pathogenic E. coli in Adler monkey colony.

PubMed

Lapin, Boris A; Yakovleva, Lelita A; Dzhikidze, Eteri K; Gvozdik, Tatiana E; Agumava, Aslan A; Stasilevich, Zinaida K; Danilova, Irina G

2015-12-01

In spring 2009 in Adler colony of the Institute of Medical Primatology, a large enzootic outbreak of acute intestine infection associated with pathogenic E. coli occurred and caused 5% mortality of population (209 animals). The epidemiological analysis, bacteriological investigation, postmortem examination, histological analysis, and PCR were used to identify the infectious agent. Marked hemorrhagic diathesis, lethargy, dehydration, diarrhea with blood, wasting, and sometimes dystrophic changes in articular cartilages were noted. Morphologically, hemorrhagic enterocolitis and massive hemorrhages were found. PCR investigation of bacteriologically isolated E. coli characterized it as enteropathogenic and enteroinvasive E. coli. The outbreak in Adler colony slightly differed from similar outbreak in Florida in 2014 by more marked hemorrhagic diathesis and articular changes in some monkeys caused by polyavitaminosis developed in the course of infection. Sensitive to infection were M. mulatta, M. fascicularis, Cercopithecus aethiops, P. hamadryas and anubis, and Cebus capucinus. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

PubMed Central

Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

2016-01-01

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

Induced responses to herbivory and jasmonate in three milkweed species.

PubMed

Rasmann, Sergio; Johnson, M Daisy; Agrawal, Anurag A

2009-11-01

We studied constitutive and induced defensive traits (latex exudation, cardenolides, proteases, and C/N ratio) and resistance to monarch caterpillars (Danaus plexippus) in three closely related milkweed species (Asclepias angustifolia, A. barjoniifolia and A. fascicularis). All traits showed significant induction in at least one of the species. Jasmonate application only partially mimicked the effect of monarch feeding. We found some correspondence between latex and cardenolide content and reduced larval growth. Larvae fed cut leaves of A. angustifolia grew better than larvae fed intact plants. Addition of the cardenolide digitoxin to cut leaves reduced larval growth but ouabain (at the same concentration) had no effect. We, thus, confirm that latex and cardenolides are major defenses in milkweeds, effective against a specialist herbivore. Other traits such as proteases and C/N ratio additionally may be integrated in the defense scheme of those plants. Induction seems to play an important role in plants that have an intermediate level of defense, and we advocate incorporating induction as an additional axis of the plant defense syndrome hypothesis.

Persistence of rabies antibody 5 years after pre-exposure prophylaxis with human diploid cell antirabies vaccine and antibody response to a single booster dose.

PubMed Central

Rodrigues, F. M.; Mandke, V. B.; Roumiantzeff, M.; Rao, C. V.; Mehta, J. M.; Pavri, K. M.; Poonawalla, C.

1987-01-01

In 1978, 22 staff members of the National Institute of Virology, Pune, India, were given two doses of human diploid cell antirabies vaccine (HDCV) for primary pre-exposure prophylactic immunization; the interval between the two doses being approximately 4 weeks. Eighteen of these 22 vaccinees were given a booster dose 1 year later. All 18 vaccinees developed protective levels of antibody; most of them had antibody levels exceeding 10 IU/ml. In 1984, 5 years after the booster dose, 11 (79.0%) of 14 vaccinees tested still possessed neutralizing antibody levels ranging from 0.5 IU/ml to 10 IU/ml. Fourteen days after the administration of a booster dose, the antibody levels ranged from 10 to greater than or equal to 100 IU/ml for all except one vaccine (5.2 IU/ml). These findings demonstrate that the majority of vaccines retained detectable neutralizing antibody after pre-exposure prophylaxis for as long as 5 years and that a single booster dose thereafter evoked a good antibody response. PMID:3609177

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).

PubMed

Maze, Ian S; Wright, Geraldine A; Mustard, Julie A

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.

Adhesive Proteins of Stalked and Acorn Barnacles Display Homology with Low Sequence Similarities

PubMed Central

Jonker, Jaimie-Leigh; Abram, Florence; Pires, Elisabete; Varela Coelho, Ana; Grunwald, Ingo; Power, Anne Marie

2014-01-01

Barnacle adhesion underwater is an important phenomenon to understand for the prevention of biofouling and potential biotechnological innovations, yet so far, identifying what makes barnacle glue proteins ‘sticky’ has proved elusive. Examination of a broad range of species within the barnacles may be instructive to identify conserved adhesive domains. We add to extensive information from the acorn barnacles (order Sessilia) by providing the first protein analysis of a stalked barnacle adhesive, Lepas anatifera (order Lepadiformes). It was possible to separate the L. anatifera adhesive into at least 10 protein bands using SDS-PAGE. Intense bands were present at approximately 30, 70, 90 and 110 kilodaltons (kDa). Mass spectrometry for protein identification was followed by de novo sequencing which detected 52 peptides of 7–16 amino acids in length. None of the peptides matched published or unpublished transcriptome sequences, but some amino acid sequence similarity was apparent between L. anatifera and closely-related Dosima fascicularis. Antibodies against two acorn barnacle proteins (ab-cp-52k and ab-cp-68k) showed cross-reactivity in the adhesive glands of L. anatifera. We also analysed the similarity of adhesive proteins across several barnacle taxa, including Pollicipes pollicipes (a stalked barnacle in the order Scalpelliformes). Sequence alignment of published expressed sequence tags clearly indicated that P. pollicipes possesses homologues for the 19 kDa and 100 kDa proteins in acorn barnacles. Homology aside, sequence similarity in amino acid and gene sequences tended to decline as taxonomic distance increased, with minimum similarities of 18–26%, depending on the gene. The results indicate that some adhesive proteins (e.g. 100 kDa) are more conserved within barnacles than others (20 kDa). PMID:25295513

Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training.

PubMed

Williams, N I; Helmreich, D L; Parfitt, D B; Caston-Balderrama, A; Cameron, J L

2001-11-01

Cross-sectional and short-term prospective studies in humans support the concept that low energy availability, and not other factors associated with exercise, causes the development of exercise-induced reproductive dysfunction. To rigorously test this hypothesis, we performed a longitudinal study, examining the role of low energy availability on both the development and the reversal of exercise-induced amenorrhea, using a monkey model (Macaca fascicularis). Eight adult female monkeys developed amenorrhea (defined as absence of menses for at least 100 d, with low and unchanging concentrations of LH, FSH, E2, and P4) after gradually increasing their daily exercise to 12.3 +/- 0.9 km/d of running over a 7- to 24-month period. Food intake remained constant during exercise training. To test whether amenorrhea is caused by low energy availability, four of the eight amenorrheic monkeys were provided with supplemental calories (138-181% of calorie intake during amenorrhea) while they maintained their daily training. All four monkeys exhibited increased reproductive hormone levels and reestablished ovulatory cycles, with recovery times for circulating gonadotropin levels ranging from 12-57 d from the initiation of supplemental feeding. The rapidity of recovery within the reproductive axis in a given monkey was directly related to the amount of energy that was consumed during the period of supplemental feeding (r = -0.97; P < 0.05). Repeated measurements of plasma T3 concentrations, a marker of cellular energy availability, revealed a tight correlation between the changes in reproductive function and T3 levels, such that T3 significantly decreased (27%) with the induction and significantly increased (18%) with the reversal of amenorrhea (P < 0.05). These data provide strong evidence that low energy availability plays a causal role in the development of exercise-induced amenorrhea.

Adhesive proteins of stalked and acorn barnacles display homology with low sequence similarities.

PubMed

Jonker, Jaimie-Leigh; Abram, Florence; Pires, Elisabete; Varela Coelho, Ana; Grunwald, Ingo; Power, Anne Marie

2014-01-01

Barnacle adhesion underwater is an important phenomenon to understand for the prevention of biofouling and potential biotechnological innovations, yet so far, identifying what makes barnacle glue proteins 'sticky' has proved elusive. Examination of a broad range of species within the barnacles may be instructive to identify conserved adhesive domains. We add to extensive information from the acorn barnacles (order Sessilia) by providing the first protein analysis of a stalked barnacle adhesive, Lepas anatifera (order Lepadiformes). It was possible to separate the L. anatifera adhesive into at least 10 protein bands using SDS-PAGE. Intense bands were present at approximately 30, 70, 90 and 110 kilodaltons (kDa). Mass spectrometry for protein identification was followed by de novo sequencing which detected 52 peptides of 7-16 amino acids in length. None of the peptides matched published or unpublished transcriptome sequences, but some amino acid sequence similarity was apparent between L. anatifera and closely-related Dosima fascicularis. Antibodies against two acorn barnacle proteins (ab-cp-52k and ab-cp-68k) showed cross-reactivity in the adhesive glands of L. anatifera. We also analysed the similarity of adhesive proteins across several barnacle taxa, including Pollicipes pollicipes (a stalked barnacle in the order Scalpelliformes). Sequence alignment of published expressed sequence tags clearly indicated that P. pollicipes possesses homologues for the 19 kDa and 100 kDa proteins in acorn barnacles. Homology aside, sequence similarity in amino acid and gene sequences tended to decline as taxonomic distance increased, with minimum similarities of 18-26%, depending on the gene. The results indicate that some adhesive proteins (e.g. 100 kDa) are more conserved within barnacles than others (20 kDa).

Differential expression of three galaxin-related genes during settlement and metamorphosis in the scleractinian coral Acropora millepora

PubMed Central

Reyes-Bermudez, Alejandro; Lin, Zhiyi; Hayward, David C; Miller, David J; Ball, Eldon E

2009-01-01

Background The coral skeleton consists of CaCO3 deposited upon an organic matrix primarily as aragonite. Currently galaxin, from Galaxea fascicularis, is the only soluble protein component of the organic matrix that has been characterized from a coral. Three genes related to galaxin were identified in the coral Acropora millepora. Results One of the Acropora genes (Amgalaxin) encodes a clear galaxin ortholog, while the others (Amgalaxin-like 1 and Amgalaxin-like 2) encode larger and more divergent proteins. All three proteins are predicted to be extracellular and share common structural features, most notably the presence of repetitive motifs containing dicysteine residues. In situ hybridization reveals distinct, but partially overlapping, spatial expression of the genes in patterns consistent with distinct roles in calcification. Both of the Amgalaxin-like genes are expressed exclusively in the early stages of calcification, while Amgalaxin continues to be expressed in the adult, consistent with the situation in the coral Galaxea. Conclusion Comparisons with molluscs suggest functional convergence in the two groups; lustrin A/pearlin proteins may be the mollusc counterparts of galaxin, whereas the galaxin-like proteins combine characteristics of two distinct proteins involved in mollusc calcification. Database searches indicate that, although sequences with high similarity to the galaxins are restricted to the Scleractinia, more divergent members of this protein family are present in other cnidarians and some other metazoans. We suggest that ancestral galaxins may have been secondarily recruited to roles in calcification in the Triassic, when the Scleractinia first appeared. Understanding the evolution of the broader galaxin family will require wider sampling and expression analysis in a range of cnidarians and other animals. PMID:19638240

Characterization of MOSFET dosimeters for low‐dose measurements in maxillofacial anthropomorphic phantoms

PubMed Central

Wolff, Jan E.; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-01-01

The aims of this study were to characterize reinforced metal‐oxide‐semiconductor field‐effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low‐dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50–90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point‐dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k=2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low‐dose limit. The sensitivity was 3.09±0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was −8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD‐comparable low‐dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low. PACS number: 87.50.wj PMID:26219008

Characterization of Thymol blue Radiochromic dosimeters for high dose applications

NASA Astrophysics Data System (ADS)

Aldweri, Feras M.; Abuzayed, Manar H.; Al-Ajaleen, Musab S.; Rabaeh, Khalid A.

2018-03-01

Thymol blue (TB) solutions and Thymol blue Polyvinyl Alcohol (TB-PVA) films have been introduced as Radiochromic dosimeter for high dose applications. The dosimeters were irradiated with gamma ray (60Co source) from 5 to 30 kGy for film, and from 0.150 kGy to 4 kGy for solution. The optical density of unirradiated and irradiated TB solution as well as TB-PVA film dosimeters were studied in terms of absorbance at 434 nm using UV/VIS spectrophotometer. The effects of scan temperature, light pre-gamma irradiation, dose rate, relative humidity and stability of the absorbance of solutions and films after irradiation were investigated. We found the dose sensitivity of TB solution and TB-PVA film dosimeters increases significantly with increases of the absorbed dose as well as with the increases of TB dye concentrations. The useful dose range of developed TB solutions and TB-PVA films dosimeters is in the range 0.125-1 kGy and of 5-20 kGy, respectively.

Psychopharmacology of theobromine in healthy volunteers.

PubMed

Baggott, Matthew J; Childs, Emma; Hart, Amy B; de Bruin, Eveline; Palmer, Abraham A; Wilkinson, Joy E; de Wit, Harriet

2013-07-01

Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.

Psychopharmacology of theobromine in healthy volunteers

PubMed Central

Baggott, Matthew J.; Childs, Emma; Hart, Amy B.; de Bruin, Eveline; Palmer, Abraham A.; Wilkinson, Joy E.; de Wit, Harriet

2013-01-01

Background Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, currently evidence for this is limited. Objectives We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Results Caffeine had the expected effects on mood including feelings of alertness, and cardiovascular parameters. Theobromine responses differed according to dose: it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses we also examined individual differences in the drugs' effects in relation to genes related to their target receptors, but few associations were detected. Conclusions This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes effects become negative. PMID:23420115

Gamma ray induced decomposition of double nitrates of lanthanum and cerium with some mono and bivalent cations in solid state

NASA Astrophysics Data System (ADS)

Kulkarni, S. P.; Garg, A. N.

Gamma ray induced decomposition of two series of double nitrates; 2M INO 3⋯Ln(NO 3) 3⋯ x H 2O (where MI = NH+4, Na+, K+, Rb+, Cs+; LnIII = La3+, Ce3+ and x = 2 or 4) and 3M II(NO 3) 2·2Ln III(NO 3) 3⋯24H 2O (where MII = Mg2+, Co2+, Zn2+; LnIII = La3+, Ce3+) has been studied in solid state over a wide absorbed dose range at room temperature. G(NO -2) values have been found to depend on the absorbed dose and the nature of cation in both the series of double salts. Radiation sensitivity of lanthanum double nitrates with monovalent cations at an absorbed dose of 158 kGy follows the order NH +4 < Rb + ≅ Cs + < Na + < K + and those of cerium NH +4 < Rb +

Pharmacokinetics and Safety of MP-376 (Levofloxacin Inhalation Solution) in Cystic Fibrosis Subjects▿

PubMed Central

Geller, David E.; Flume, Patrick A.; Griffith, David C.; Morgan, Elizabeth; White, Dan; Loutit, Jeffery S.; Dudley, Michael N.

2011-01-01

The pharmacokinetics and tolerability of nebulized MP-376 (levofloxacin inhalation solution [Aeroquin]) were determined in cystic fibrosis (CF) subjects. Ten CF subjects received single 180-mg doses of two formulations of MP-376, followed by a multiple-dose phase of 240 mg once daily for 7 days. Serum and expectorated-sputum samples were assayed for levofloxacin content. Safety was evaluated following the single- and multiple-dose study phases. Nebulized MP-376 produced high concentrations of levofloxacin in sputum. The mean maximum plasma concentration (Cmax) ranged between 2,563 and 2,932 mg/liter for 180-mg doses of the 50- and 100-mg/ml formulations, respectively. After 7 days of dosing, the mean Cmax for the 240-mg dose was 4,691 mg/liter. The mean serum levofloxacin Cmax ranged between 0.95 and 1.28 for the 180-mg doses and was 1.71 for the 240-mg dose. MP-376 was well tolerated. Nebulized MP-376 produces high sputum and low serum levofloxacin concentrations. The pharmacokinetics, safety, and tolerability were similar for the two formulations. MP-376 240 mg (100 mg/ml) is being advanced into late-stage clinical development. PMID:21444699

Radiation Dose to the Lens of the Eye from Computed Tomography Scans of the Head

NASA Astrophysics Data System (ADS)

Januzis, Natalie Ann

While it is well known that exposure to radiation can result in cataract formation, questions still remain about the presence of a dose threshold in radiation cataractogenesis. Since the exposure history from diagnostic CT exams is well documented in a patient's medical record, the population of patients chronically exposed to radiation from head CT exams may be an interesting area to explore for further research in this area. However, there are some challenges in estimating lens dose from head CT exams. An accurate lens dosimetry model would have to account for differences in imaging protocols, differences in head size, and the use of any dose reduction methods. The overall objective of this dissertation was to develop a comprehensive method to estimate radiation dose to the lens of the eye for patients receiving CT scans of the head. This research is comprised of a physics component, in which a lens dosimetry model was derived for head CT, and a clinical component, which involved the application of that dosimetry model to patient data. The physics component includes experiments related to the physical measurement of the radiation dose to the lens by various types of dosimeters placed within anthropomorphic phantoms. These dosimeters include high-sensitivity MOSFETs, TLDs, and radiochromic film. The six anthropomorphic phantoms used in these experiments range in age from newborn to adult. First, the lens dose from five clinically relevant head CT protocols was measured in the anthropomorphic phantoms with MOSFET dosimeters on two state-of-the-art CT scanners. The volume CT dose index (CTDIvol), which is a standard CT output index, was compared to the measured lens doses. Phantom age-specific CTDIvol-to-lens dose conversion factors were derived using linear regression analysis. Since head size can vary among individuals of the same age, a method was derived to estimate the CTDIvol-to-lens dose conversion factor using the effective head diameter. These conversion factors were derived for each scanner individually, but also were derived with the combined data from the two scanners as a means to investigate the feasibility of a scanner-independent method. Using the scanner-independent method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter, most of the fitted lens dose values fell within 10-15% of the measured values from the phantom study, suggesting that this is a fairly accurate method of estimating lens dose from the CTDIvol with knowledge of the patient's head size. Second, the dose reduction potential of organ-based tube current modulation (OB-TCM) and its effect on the CTDIvol-to-lens dose estimation method was investigated. The lens dose was measured with MOSFET dosimeters placed within the same six anthropomorphic phantoms. The phantoms were scanned with the five clinical head CT protocols with OB-TCM enabled on the one scanner model at our institution equipped with this software. The average decrease in lens dose with OB-TCM ranged from 13.5 to 26.0%. Using the size-specific method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter for protocols with OB-TCM, the majority of the fitted lens dose values fell within 15-18% of the measured values from the phantom study. Third, the effect of gantry angulation on lens dose was investigated by measuring the lens dose with TLDs placed within the six anthropomorphic phantoms. The 2-dimensional spatial distribution of dose within the areas of the phantoms containing the orbit was measured with radiochromic film. A method was derived to determine the CTDIvol-to-lens dose conversion factor based upon distance from the primary beam scan range to the lens. The average dose to the lens region decreased substantially for almost all the phantoms (ranging from 67 to 92%) when the orbit was exposed to scattered radiation compared to the primary beam. The effectiveness of this method to reduce lens dose is highly dependent upon the shape and size of the head, which influences whether or not the angled scan range coverage can include the entire brain volume and still avoid the orbit. The clinical component of this dissertation involved performing retrospective patient studies in the pediatric and adult populations, and reconstructing the lens doses from head CT examinations with the methods derived in the physics component. The cumulative lens doses in the patients selected for the retrospective study ranged from 40 to 1020 mGy in the pediatric group, and 53 to 2900 mGy in the adult group. This dissertation represents a comprehensive approach to lens of the eye dosimetry in CT imaging of the head. The collected data and derived formulas can be used in future studies on radiation-induced cataracts from repeated CT imaging of the head. Additionally, it can be used in the areas of personalized patient dose management, and protocol optimization and clinician training.

A rule-based, dose-finding design for use in stroke rehabilitation research: methodological development.

PubMed

Colucci, E; Clark, A; Lang, C E; Pomeroy, V M

2017-12-01

Dose-optimisation studies as precursors to clinical trials are rare in stroke rehabilitation. To develop a rule-based, dose-finding design for stroke rehabilitation research. 3+3 rule-based, dose-finding study. Dose escalation/de-escalation was undertaken according to preset rules and a mathematical sequence (modified Fibonacci sequence). The target starting daily dose was 50 repetitions for the first cohort. Adherence was recorded by an electronic counter. At the end of the 2-week training period, the adherence record indicated dose tolerability (adherence to target dose) and the outcome measure indicated dose benefit (10% increase in motor function). The preset increment/decrease and checking rules were then applied to set the dose for the subsequent cohort. The process was repeated until preset stopping rules were met. Participants had a mean age of 68 (range 48 to 81) years, and were a mean of 70 (range 9 to 289) months post stroke with moderate upper limb paresis. A custom-built model of exercise-based training to enhance ability to open the paretic hand. Repetitions per minute of extension/flexion of paretic digits against resistance. Usability of the preset rules and whether the maximally tolerated dose was identifiable. Five cohorts of three participants were involved. Discernibly different doses were set for each subsequent cohort (i.e. 50, 100, 167, 251 and 209 repetitions/day). The maximally tolerated dose for the model training task was 209 repetitions/day. This dose-finding design is a feasible method for use in stroke rehabilitation research. Copyright © 2017 Chartered Society of Physiotherapy. All rights reserved.

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Prospective study of direct radiation exposure measurements for family members living with patients with prostate (125)I seed implantation: Evidence of radiation safety.

PubMed

Hanada, Takashi; Yorozu, Atsunori; Shinya, Yukiko; Kuroiwa, Nobuko; Ohashi, Toshio; Saito, Shiro; Shigematsu, Naoyuki

2016-01-01

To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to (125)I seed implantation. Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent (125)I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. Our study demonstrated low radiation exposures to family members of patients undergoing (125)I prostate implantation. It was clear that (125)I seed implantation did not pose a threat to the safety of family members. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Organ doses, effective doses, and risk indices in adult CT: Comparison of four types of reference phantoms across different examination protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Yakun; Li Xiang; Paul Segars, W.

Purpose: Radiation exposure from computed tomography (CT) to the public has increased the concern among radiation protection professionals. Being able to accurately assess the radiation dose patients receive during CT procedures is a crucial step in the management of CT dose. Currently, various computational anthropomorphic phantoms are used to assess radiation dose by different research groups. It is desirable to better understand how the dose results are affected by different choices of phantoms. In this study, the authors assessed the uncertainties in CT dose and risk estimation associated with different types of computational phantoms for a selected group of representativemore » CT protocols. Methods: Routinely used CT examinations were categorized into ten body and three neurological examination categories. Organ doses, effective doses, risk indices, and conversion coefficients to effective dose and risk index (k and q factors, respectively) were estimated for these examinations for a clinical CT system (LightSpeed VCT, GE Healthcare). Four methods were used, each employing a different type of reference phantoms. The first and second methods employed a Monte Carlo program previously developed and validated in our laboratory. In the first method, the reference male and female extended cardiac-torso (XCAT) phantoms were used, which were initially created from the Visible Human data and later adjusted to match organ masses defined in ICRP publication 89. In the second method, the reference male and female phantoms described in ICRP publication 110 were used, which were initially developed from tomographic data of two patients and later modified to match ICRP 89 organ masses. The third method employed a commercial dosimetry spreadsheet (ImPACT group, London, England) with its own hermaphrodite stylized phantom. In the fourth method, another widely used dosimetry spreadsheet (CT-Expo, Medizinische Hochschule, Hannover, Germany) was employed together with its associated male and female stylized phantoms. Results: For fully irradiated organs, average coefficients of variation (COV) ranged from 0.07 to 0.22 across the four male phantoms and from 0.06 to 0.18 across the four female phantoms; for partially irradiated organs, average COV ranged from 0.13 to 0.30 across the four male phantoms and from 0.15 to 0.30 across the four female phantoms. Doses to the testes, breasts, and esophagus showed large variations between phantoms. COV for gender-averaged effective dose and k factor ranged from 0.03 to 0.23 and from 0.06 to 0.30, respectively. COV for male risk index and q factor ranged from 0.06 to 0.30 and from 0.05 to 0.36, respectively; COV for female risk index and q factor ranged from 0.06 to 0.49 and from 0.07 to 0.54, respectively. Conclusions: Despite closely matched organ mass, total body weight, and height, large differences in organ dose exist due to variation in organ location, spatial distribution, and dose approximation method. Dose differences for fully irradiated radiosensitive organs were much smaller than those for partially irradiated organs. Weighted dosimetry quantities including effective dose, male risk indices, k factors, and male q factors agreed well across phantoms. The female risk indices and q factors varied considerably across phantoms.« less

Organ doses, effective doses, and risk indices in adult CT: Comparison of four types of reference phantoms across different examination protocols

PubMed Central

Zhang, Yakun; Li, Xiang; Paul Segars, W.; Samei, Ehsan

2012-01-01

Purpose: Radiation exposure from computed tomography (CT) to the public has increased the concern among radiation protection professionals. Being able to accurately assess the radiation dose patients receive during CT procedures is a crucial step in the management of CT dose. Currently, various computational anthropomorphic phantoms are used to assess radiation dose by different research groups. It is desirable to better understand how the dose results are affected by different choices of phantoms. In this study, the authors assessed the uncertainties in CT dose and risk estimation associated with different types of computational phantoms for a selected group of representative CT protocols. Methods: Routinely used CT examinations were categorized into ten body and three neurological examination categories. Organ doses, effective doses, risk indices, and conversion coefficients to effective dose and risk index (k and q factors, respectively) were estimated for these examinations for a clinical CT system (LightSpeed VCT, GE Healthcare). Four methods were used, each employing a different type of reference phantoms. The first and second methods employed a Monte Carlo program previously developed and validated in our laboratory. In the first method, the reference male and female extended cardiac-torso (XCAT) phantoms were used, which were initially created from the Visible Human data and later adjusted to match organ masses defined in ICRP publication 89. In the second method, the reference male and female phantoms described in ICRP publication 110 were used, which were initially developed from tomographic data of two patients and later modified to match ICRP 89 organ masses. The third method employed a commercial dosimetry spreadsheet (ImPACT group, London, England) with its own hermaphrodite stylized phantom. In the fourth method, another widely used dosimetry spreadsheet (CT-Expo, Medizinische Hochschule, Hannover, Germany) was employed together with its associated male and female stylized phantoms. Results: For fully irradiated organs, average coefficients of variation (COV) ranged from 0.07 to 0.22 across the four male phantoms and from 0.06 to 0.18 across the four female phantoms; for partially irradiated organs, average COV ranged from 0.13 to 0.30 across the four male phantoms and from 0.15 to 0.30 across the four female phantoms. Doses to the testes, breasts, and esophagus showed large variations between phantoms. COV for gender-averaged effective dose and k factor ranged from 0.03 to 0.23 and from 0.06 to 0.30, respectively. COV for male risk index and q factor ranged from 0.06 to 0.30 and from 0.05 to 0.36, respectively; COV for female risk index and q factor ranged from 0.06 to 0.49 and from 0.07 to 0.54, respectively. Conclusions: Despite closely matched organ mass, total body weight, and height, large differences in organ dose exist due to variation in organ location, spatial distribution, and dose approximation method. Dose differences for fully irradiated radiosensitive organs were much smaller than those for partially irradiated organs. Weighted dosimetry quantities including effective dose, male risk indices, k factors, and male q factors agreed well across phantoms. The female risk indices and q factors varied considerably across phantoms. PMID:22755721

Proposed linear energy transfer areal detector for protons using radiochromic film.

PubMed

Mayer, Rulon; Lin, Liyong; Fager, Marcus; Douglas, Dan; McDonough, James; Carabe, Alejandro

2015-04-01

Radiation therapy depends on predictably and reliably delivering dose to tumors and sparing normal tissues. Protons with kinetic energy of a few hundred MeV can selectively deposit dose to deep seated tumors without an exit dose, unlike x-rays. The better dose distribution is attributed to a phenomenon known as the Bragg peak. The Bragg peak is due to relatively high energy deposition within a given distance or high Linear Energy Transfer (LET). In addition, biological response to radiation depends on the dose, dose rate, and localized energy deposition patterns or LET. At present, the LET can only be measured at a given fixed point and the LET spatial distribution can only be inferred from calculations. The goal of this study is to develop and test a method to measure LET over extended areas. Traditionally, radiochromic films are used to measure dose distribution but not for LET distribution. We report the first use of these films for measuring the spatial distribution of the LET deposited by protons. The radiochromic film sensitivity diminishes for large LET. A mathematical model correlating the film sensitivity and LET is presented to justify relating LET and radiochromic film relative sensitivity. Protons were directed parallel to radiochromic film sandwiched between solid water slabs. This study proposes the scaled-normalized difference (SND) between the Treatment Planning system (TPS) and measured dose as the metric describing the LET. The SND is correlated with a Monte Carlo (MC) calculation of the LET spatial distribution for a large range of SNDs. A polynomial fit between the SND and MC LET is generated for protons having a single range of 20 cm with narrow Bragg peak. Coefficients from these fitted polynomial fits were applied to measured proton dose distributions with a variety of ranges. An identical procedure was applied to the protons deposited from Spread Out Bragg Peak and modulated by 5 cm. Gamma analysis is a method for comparing the calculated LET with the LET measured using radiochromic film at the pixel level over extended areas. Failure rates using gamma analysis are calculated for areas in the dose distribution using parameters of 25% of MC LET and 3 mm. The processed dose distributions find 5%-10% failure rates for the narrow 12.5 and 15 cm proton ranges and 10%-15% for proton ranges of 15, 17.5, and 20 cm and modulated by 5 cm. It is found through gamma analysis that the measured proton energy deposition in radiochromic film and TPS can be used to determine LET. This modified film dosimetry provides an experimental areal LET measurement that can verify MC calculations, support LET point measurements, possibly enhance biologically based proton treatment planning, and determine the polymerization process within the radiochromic film.

A Radiobiological Analysis of Multicenter Data for Postoperative Keloid Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flickinger, John C., E-mail: flickingerjc@upmc.ed

2011-03-15

Purpose: To identify factors significantly affecting recurrence rates after postoperative external beam radiotherapy (XRT) of keloids, and to delineate any radiation dose response and effects of radiation dose per fraction. Methods and Materials: A comprehensive literature review was performed to compile a database of 2,515 resected keloids (36.9% earlobe). Postoperative XRT was 45- to 100-kV X-rays in 27.0% or 120- to 250-kV X-rays in 11.1%, Co-60 in 1.9%, Sr-90 in 4.7%, 1.5- to 9-MeV electrons in 26.5%, and no XRT in 28.8%. In the 1,791 irradiated patients, the median radiation parameters were as follows: total dose, 15 Gy (range, 6-30more » Gy); dose per fraction, 5.0 Gy (range, 2-15 Gy); fractions, 3 (range, 1-10); and time, 7 days (range, 0-33 days). Results: Multivariate stepwise logistic regression correlated decreased keloid recurrence with earlobe location (p = 1.98E-10; odds ratio, 0.34), biologically effective dose (p = 1.01E-27), and treatment with electron beam or Co-60 vs. other techniques (p = 0.0014; odds ratio, 0.72). Different radiobiological models calculated values of {alpha}/{beta} = 1.12 to 2.86 (mean, 2.08) and time (repopulation) correction factors for biologically effective dose from 0.98 to 2.13 Gy per day (mean, 1.34) starting 10 days after surgery. Different models (with {alpha}/{beta} = 2.08) predicted that doses needed for 90% and 95% control with 3 fractions of postoperative electron beam were 16.0 to 16.2 Gy and 18.3 to 19.2 Gy, respectively, in less than 10 days for earlobe keloids and 21.5 to 22.2 Gy and 23.4 to 24.8 Gy, respectively, in less than 10 days for other sites. Conclusions: Postoperative keloid radiotherapy requires moderately high doses and optimal technique to be effective. The relatively low {alpha}/{beta} ratio indicates that radiotherapy with a limited number of fractions and high doses per fraction is the best strategy.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Eugene; Corbett, James R.; Moran, Jean M.

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

Patient-specific dose calculations for pediatric CT of the chest, abdomen and pelvis

PubMed Central

Fraser, Nicholas D.; Carver, Diana E.; Pickens, David R.; Price, Ronald R.; Hernanz-Schulman, Marta; Stabin, Michael G.

2015-01-01

Background Organ dose is essential for accurate estimates of patient dose from CT. Objective To determine organ doses from a broad range of pediatric patients undergoing diagnostic chest–abdomen–pelvis CT and investigate how these relate to patient size. Materials and methods We used a previously validated Monte Carlo simulation model of a Philips Brilliance 64 multi-detector CT scanner (Philips Healthcare, Best, The Netherlands) to calculate organ doses for 40 pediatric patients (M:F=21:19; range 0.6–17 years). Organ volumes and positions were determined from the images using standard segmentation techniques. Non-linear regression was performed to determine the relationship between volume CT dose index (CTDIvol)-normalized organ doses and abdominopelvic diameter. We then compared results with values obtained from independent studies. Results We found that CTDIvol-normalized organ dose correlated strongly with exponentially decreasing abdominopelvic diameter (R2>0.8 for most organs). A similar relationship was determined for effective dose when normalized by dose-length product (R2=0.95). Our results agreed with previous studies within 12% using similar scan parameters (i.e. bowtie filter size, beam collimation); however results varied up to 25% when compared to studies using different bowtie filters. Conclusion Our study determined that organ doses can be estimated from measurements of patient size, namely body diameter, and CTDIvol prior to CT examination. This information provides an improved method for patient dose estimation. PMID:26142256

Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

PubMed

Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

2018-06-01

To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

Population pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium in pediatric patients, adult patients, and healthy volunteers.

PubMed

Tanaka, Jun; Kasai, Hidefumi; Shimizu, Kenji; Shimasaki, Shigeki; Kumagai, Yuji

2013-03-01

We performed a population pharmacokinetic analysis of phenytoin after intravenous administration of fosphenytoin sodium in healthy, neurosurgical, and epileptic subjects, including pediatric patients, and determined the optimal dose and infusion rate for achieving the therapeutic range. We used pooled data obtained from two phase I studies and one phase III study performed in Japan. The population pharmacokinetic analysis was performed using NONMEM software. The optimal dose and infusion rate were determined using simulation results obtained using the final model. The therapeutic range for total plasma phenytoin concentration is 10-20 μg/mL. We used a linear two-compartment model with conversion of fosphenytoin to phenytoin. Pharmacokinetic parameters of phenytoin, such as total clearance and central and peripheral volume of distribution were influenced by body weight. The dose simulations are as follows. In adult patients, the optimal dose and infusion rate of phenytoin for achieving the therapeutic range was 22.5 mg/kg and 3 mg/kg/min respectively. In pediatric patients, the total plasma concentration of phenytoin was within the therapeutic range for a shorter duration than that in adult patients at 22.5 mg/kg (3 mg/kg/min). However, many pediatric patients showed phenytoin concentration within the toxic range after administration of a dose of 30 mg/kg. The pharmacokinetics of phenytoin after intravenous administration of fosphenytoin sodium could be described using a linear two-compartment model. The administration of fosphenytoin sodium 22.5 mg/kg at an infusion rate of 3 mg/kg/min was optimal for achieving the desired plasma phenytoin concentration.

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

Accuracy of micro powder dosing via a vibratory sieve-chute system.

PubMed

Besenhard, M O; Faulhammer, E; Fathollahi, S; Reif, G; Calzolari, V; Biserni, S; Ferrari, A; Lawrence, S M; Llusa, M; Khinast, J G

2015-08-01

This paper describes a powder dosing system with a vibratory sieve mounted on a chute that doses particles into a capsule. Vertical vibration occurred with a broad range of frequencies and amplitudes. During dosing events, the fill weight was accurately recorded via a capacitance sensor, covering the capsules and making it possible to analyze filling characteristics, that is, the fill rates and their robustness. The range of frequencies and amplitudes was screened for settings that facilitated reasonable (no blocking, no spilling) fill rates for three lactose powders. The filling characteristics were studied within this operating space. The results reveal similar operating spaces for all investigated powders. The fill rate robustness varied distinctly in the operating space, which is of prime importance for selecting the settings for continuous feeding applications. In addition, we present accurate dosing studies utilizing the knowledge about the filling characteristics of each powder. Copyright © 2015 Elsevier B.V. All rights reserved.

From prompt gamma distribution to dose: a novel approach combining an evolutionary algorithm and filtering based on Gaussian-powerlaw convolutions.

PubMed

Schumann, A; Priegnitz, M; Schoene, S; Enghardt, W; Rohling, H; Fiedler, F

2016-10-07

Range verification and dose monitoring in proton therapy is considered as highly desirable. Different methods have been developed worldwide, like particle therapy positron emission tomography (PT-PET) and prompt gamma imaging (PGI). In general, these methods allow for a verification of the proton range. However, quantification of the dose from these measurements remains challenging. For the first time, we present an approach for estimating the dose from prompt γ-ray emission profiles. It combines a filtering procedure based on Gaussian-powerlaw convolution with an evolutionary algorithm. By means of convolving depth dose profiles with an appropriate filter kernel, prompt γ-ray depth profiles are obtained. In order to reverse this step, the evolutionary algorithm is applied. The feasibility of this approach is demonstrated for a spread-out Bragg-peak in a water target.

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

PubMed

Batschinski, K; Dervisis, N G; Kitchell, B E

2014-12-01

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

MCNPX simulation of proton dose distribution in homogeneous and CT phantoms

NASA Astrophysics Data System (ADS)

Lee, C. C.; Lee, Y. J.; Tung, C. J.; Cheng, H. W.; Chao, T. C.

2014-02-01

A dose simulation system was constructed based on the MCNPX Monte Carlo package to simulate proton dose distribution in homogeneous and CT phantoms. Conversion from Hounsfield unit of a patient CT image set to material information necessary for Monte Carlo simulation is based on Schneider's approach. In order to validate this simulation system, inter-comparison of depth dose distributions among those obtained from the MCNPX, GEANT4 and FLUKA codes for a 160 MeV monoenergetic proton beam incident normally on the surface of a homogeneous water phantom was performed. For dose validation within the CT phantom, direct comparison with measurement is infeasible. Instead, this study took the approach to indirectly compare the 50% ranges (R50%) along the central axis by our system to the NIST CSDA ranges for beams with 160 and 115 MeV energies. Comparison result within the homogeneous phantom shows good agreement. Differences of simulated R50% among the three codes are less than 1 mm. For results within the CT phantom, the MCNPX simulated water equivalent Req,50% are compatible with the CSDA water equivalent ranges from the NIST database with differences of 0.7 and 4.1 mm for 160 and 115 MeV beams, respectively.

Organ dose assessment in pediatric fluoroscopy and CT via a tomographic computational phantom of the newborn patient

NASA Astrophysics Data System (ADS)

Staton, Robert J.

Of the various types of imaging modalities used in pediatric radiology, fluoroscopy and computed tomography (CT) have the highest associated radiation dose. While these examinations are commonly used for pediatric patients, little data exists on the magnitude of the organ and effective dose values for these procedures. Calculation of these dose values is necessary because of children's increased sensitivity to radiation and their long life expectancy for which to express radiation's latent effects. In this study, a newborn tomographic phantom has been implemented in a radiation transport code to evaluate organ and effective doses for newborn patients in commonly performed fluoroscopy and CT examinations. Organ doses were evaluated for voiding cystourethrogram (VCUG) fluoroscopy studies of infant patients. Time-sequence analysis was performed for videotaped VCUG studies of five different patients. Organ dose values were then estimated for each patient through Monte Carlo (MC) simulations. The effective dose values of the VCUG examination for five patients ranged from 0.6 mSv to 3.2 mSv, with a mean of 1.8 +/- 0.9 mSv. Organ doses were also assessed for infant upper gastrointestinal (UGI) fluoroscopy exams. The effective dose values of the UGI examinations for five patients ranged from 1.05 mSv to 5.92 mSv, with a mean of 2.90 +/- 1.97 mSv. MC simulations of helical multislice CT (MSCT) exams were also completed using, the newborn tomographic phantom and a stylized newborn phantom. The helical path of the source, beam shaping filter, beam profile, patient table, were all included in the MC simulations of the helical MSCT scanner. Organ doses and effective doses and their dependence on scan parameters were evaluated for newborn patients. For all CT scans, the effective dose was found to range approximately 1-13 mSv, with the largest values occurring for CAP scans. Tube current modulation strategies to reduce patient dose were also evaluated for newborn patients. Overall, utilization of the newborn tomographic phantom in MC simulations has shown the need for and usefulness of pediatric tomographic phantoms. The newborn tomographic model has shown more versatility and realistic anatomical modeling when compared to the existing stylized newborn phantom. This work has provided important organ dose data for infant patients in common examinations in pediatric radiology.

Correlation of Planned Dose to Area Postrema and Dorsal Vagal Complex with Clinical Symptoms of Nausea and Vomiting in Oropharyngeal Cancer (OPC) patients treated with radiation alone using IMRT.

PubMed

Wang, Tony J C; Fontenla, Sandra; McCann, Patrick; Young, Robert J; McNamara, Stephen; Rao, Shyam; Mechalakos, James G; Lee, Nancy Y

2013-12-01

To correlate the planned dose to the nausea center (NC) - area postrema (AP) and dorsal vagal complex (DVC) - with nausea and vomiting symptoms in OPC patients treated with IMRT without chemotherapy. We also investigated whether it was possible to reduce doses to the NC without significant degradation of the clinically accepted treatment plan. From 11/04 to 4/09, 37 OPC patients were treated with definitive or adjuvant IMRT without chemotherapy. Of these, only 23 patients had restorable plans and were included in this analysis. We contoured the NC with the assistance of an expert board-certified neuroradiologist. We searched for correlation between the delivered dose to the NC and patient-reported nausea and vomiting during IMRT. We used one-paired t-test: two-sample assuming equal variances to compare differences in dose to NC between symptomatic and asymptomatic patients. We then replanned each case to determine if reduced dose to the NC could be achieved without compromising coverage to target volumes, increasing unwarranted hotspots or increasing dose to surrounding critical normal tissues. Acute symptoms of nausea were as follows: Grade 0 (n=6), Grade 1 (n=13), Grade 2 (n=3), and Grade 3 (n=1). Patients with no complaints of nausea had a median dose to the DVC of 34.2 Gy (range 4.6-46.6 Gy) and AP of 32.6 Gy (range 7.0-41.4Gy); whereas those with any complaints of nausea had a median DVC dose of 40.4 Gy (range 19.3-49.4 Gy) and AP dose of 38.7 Gy (range 16.7-46.8 Gy) (p=0.04). Acute vomiting was as follows: Grade 0 (n=17), Grade 1 (n=4), Grade 2 (n=1), and Grade 3 (n=1). There was no significant difference in DVC or AP dose among those with and without vomiting symptoms (p=0.28).Upon replanning of each case to minimize dose to the NC, we were, on average, able to reduce the radiation dose to AP by 18% and DVC by 17%; while the average dose variations to the PTV coverage, brainstem, cord, temporal lobes, and cochlea were never greater than 3%. Hotspots increased by 2% for 3 patients while hotspots for remaining patients were less than 2% variation. For OPC cancer patients treated with IMRT without chemotherapy, dose to AP and DVC may be associated with development of nausea. We were able to show that reducing doses substantially to the NC is achievable without significant alteration of the clinically accepted plan and may reduce the incidence and grade of nausea. As symptoms of nausea can be devastating to patients, one can consider routine contouring and constraining of the NC to minimize chances of having this complication.

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

NASA Astrophysics Data System (ADS)

Osman, N. D.; Shamsuri, S. B. M.; Tan, Y. W.; Razali, M. A. S. M.; Isa, S. M.

2017-05-01

Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDIvol and CTDIw) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDIw ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients.

Effective radiation dose and eye lens dose in dental cone beam CT: effect of field of view and angle of rotation.

PubMed

Pauwels, R; Zhang, G; Theodorakou, C; Walker, A; Bosmans, H; Jacobs, R; Bogaerts, R; Horner, K

2014-10-01

To quantify the effect of field of view (FOV) and angle of rotation on radiation dose in dental cone beam CT (CBCT) and to define a preliminary volume-dose model. Organ and effective doses were estimated using 148 thermoluminescent dosemeters placed in an anthropomorphic phantom. Dose measurements were undertaken on a 3D Accuitomo 170 dental CBCT unit (J. Morita, Kyoto, Japan) using six FOVs as well as full-rotation (360°) and half-rotation (180°) protocols. For the 360° rotation protocols, effective dose ranged between 54 µSv (4 × 4 cm, upper canine) and 303 µSv (17 × 12 cm, maxillofacial). An empirical relationship between FOV dimension and effective dose was derived. The use of a 180° rotation resulted in an average dose reduction of 45% compared with a 360° rotation. Eye lens doses ranged between 95 and 6861 µGy. Significant dose reduction can be achieved by reducing the FOV size, particularly the FOV height, of CBCT examinations to the actual region of interest. In some cases, a 180° rotation can be preferred, as it has the added value of reducing the scan time. Eye lens doses should be reduced by decreasing the height of the FOV rather than using inferior FOV positioning, as the latter would increase the effective dose considerably. The effect of the FOV and rotation angle on the effective dose in dental CBCT was quantified. The dominant effect of FOV height was demonstrated. A preliminary model has been proposed, which could be used to predict effective dose as a function of FOV size and position.

Reconstruction of paediatric organ doses from axial CT scans performed in the 1990s - range of doses as input to uncertainty estimates.

PubMed

Olerud, Hilde M; Toft, Benthe; Flatabø, Silje; Jahnen, Andreas; Lee, Choonsik; Thierry-Chef, Isabelle

2016-09-01

To assess the range of doses in paediatric CT scans conducted in the 1990s in Norway as input to an international epidemiology study: the EPI-CT study, http://epi-ct.iarc.fr/ . National Cancer Institute dosimetry system for Computed Tomography (NCICT) program based on pre-calculated organ dose conversion coefficients was used to convert CT Dose Index to organ doses in paediatric CT in the 1990s. Protocols reported from local hospitals in a previous Norwegian CT survey were used as input, presuming these were used without optimization for paediatric patients. Large variations in doses between different scanner models and local scan parameter settings are demonstrated. Small children will receive a factor of 2-3 times higher doses compared with adults if the protocols are not optimized for them. For common CT examinations, the doses to the active bone marrow, breast tissue and brain may have exceeded 30 mGy, 60 mGy and 100 mGy respectively, for the youngest children in the 1990s. The doses children received from non-optimised CT examinations during the 1990s are of such magnitude that they may provide statistically significant effects in the EPI-CT study, but probably do not reflect current practice. • Some organ doses from paediatric CT in the 1990s may have exceeded 100 mGy. • Small children may have received doses 2-3 times higher compared with adults. • Different scanner models varied by a factor of 2-3 in dose to patients. • Different local scan parameter settings gave dose variations of a factor 2-3. • Modern CTs and age-adjusted protocols will give much lower paediatric doses.

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Kodak EDR2 film for patient skin dose assessment in cardiac catheterization procedures.

PubMed

Morrell, R E; Rogers, A T

2006-07-01

Patient skin doses were measured using Kodak EDR2 film for 20 coronary angiography (CA) and 32 percutaneous transluminal coronary angioplasty (PTCA) procedures. For CA, all skin doses were well below 1 Gy. However, 23% of PTCA patients received skin doses of 1 Gy or more. Dose-area product (DAP) was also recorded and was found to be an inadequate indicator of maximum skin dose. Practical compliance with ICRP recommendations requires a robust method for skin dosimetry that is more accurate than DAP and is applicable over a wider dose range than EDR2 film.

Dosimetric characteristics of PASSAG as a new polymer gel dosimeter with negligible toxicity

NASA Astrophysics Data System (ADS)

Farhood, Bagher; Abtahi, Seyed Mohammad Mahdi; Geraily, Ghazale; Ghorbani, Mehdi; Mahdavi, Seied Rabi; Zahmatkesh, Mohammad Hasan

2018-06-01

Despite many advantages of polymer gel dosimeters, their clinical use is only not realized now. Toxicity of polymer gel dosimeters can be considered as one of their main limitations for use in routine clinical applications. In the current study, a new polymer gel dosimeter is introduced with negligible toxicity. For this purpose, 2-Acrylamido-2-Methy-1-PropaneSulfonic acid (AMPS) sodium salt monomer was replaced instead of acrylamide monomer used in PAGAT gel dosimeter by using %6 T and %50 C to the gel formula and the new formulation is called PASSAG (Poly AMPS Sodium Salt and Gelatin) polymer gel dosimeter. The irradiation of gel dosimeters was carried out using a Co-60 therapy machine. MRI technique was used to quantify the dose responses of the PASSAG gel dosimeter. Then, the MRI responses (R2) of the gel dosimeter was analyzed at different dose values, post-irradiation times, and scanning temperatures. The results showed that the new gel formulation has a negligible toxicity and it is also eco-friendly. In addition, carcinogenicity and genetic toxicity tests are negative for the monomer used in PASSAG. The radiological properties of PASSAG gel dosimeter showed that this substance can be considered as a soft tissue/water equivalent material. Furthermore, dosimetric evaluation of the new polymer gel dosimeter revealed an excellent linear R2-dose response in the evaluated dose range (0-15 Gy). The R2-dose sensitivity and dose resolution of PASSAG gel dosimeter were 0.081 s-1Gy-1 (in 0-15 Gy dose range) and 1 Gy (in 0-10 Gy dose range), respectively. Moreover, it was shown that the R2-dose sensitivity and dose resolution of the new gel dosimeter improves over time after irradiation. It was also found that the R2 response of the PASSAG gel dosimeter has less dependency to the 18, 20, and 24 °C scanning temperature in comparison to that of room temperature (22 °C).

EPR/alanine dosimetry for two therapeutic proton beams

NASA Astrophysics Data System (ADS)

Marrale, Maurizio; Carlino, Antonio; Gallo, Salvatore; Longo, Anna; Panzeca, Salvatore; Bolsi, Alessandra; Hrbacek, Jan; Lomax, Tony

2016-02-01

In this work the analysis of the electron paramagnetic resonance (EPR) response of alanine pellets exposed to two different clinical proton beams employed for radiotherapy is performed. One beam is characterized by a passive delivery technique and is dedicated to the eyes treatment (OPTIS2 beam line). Alanine pellets were irradiated with a 70 MeV proton beam corresponding to 35 mm range in eye tissue. We investigated how collimators with different sizes and shape used to conform the dose to the planned target volume influence the delivered dose. For this purpose we performed measurements with varying the collimator size (Output Factor) and the results were compared with those obtained with other dosimetric techniques (such as Markus chamber and diode detector). This analysis showed that the dosimeter response is independent of collimator diameter if this is larger than or equal to 10 mm. The other beam is characterized by an active spot-scanning technique, the Gantry1 beam line (maximum energy 230 MeV), and is used to treat deep-seated tumors. The dose linearity of alanine response in the clinical dose range was tested and the alanine dose response at selected locations in depth was measured and compared with the TPS planned dose in a quasi-clinical scenario. The alanine response was found to be linear in the dose in the clinical explored range (from 10 to 70 Gy). Furthermore, a depth dose profile in a quasi-clinical scenario was measured and compared to the dose computed by the Treatment Planning System PSIPLAN. The comparison of calibrated proton alanine measurements and TPS dose shows a difference under 1% in the SOBP and a "quenching" effect up to 4% in the distal part of SOBP. The positive dosimetric characteristics of the alanine pellets confirm the feasibility to use these detectors for "in vivo" dosimetry in clinical proton beams.