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Sample records for 28-day repeat dose

  1. Acute and repeated dose (28 days) oral safety studies of ALIBIRD in rats.

    Science.gov (United States)

    Anadón, Arturo; Martínez, María A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo, Nieves; Olano, Agustin; Montilla, Antonia; Recio, Isidra; Martínez-Maqueda, Daniel; Miralles, Beatriz; Fornari, Tiziana; García-Risco, Mónica R; Gonzalez, Monserrat; Reglero, Guillermo

    2013-07-01

    ALIBIRD, a test substance composed of oligosaccharides derived from lactulose, a hydrolysate of a whey protein concentrate, and a supercritical extract of rosemary (1:0.5:0.05), was prepared in the laboratory and evaluated for its safety as a multifunctional food additive. In oral toxicity studies (acute and 28 days repeated dose) using Wistar rats, ALIBIRD was administered in a single oral gavage dose of 2,000 mg/kg of body weight and resulted in no adverse events or mortality; a daily dose of 2,000 mg/kg of body weight for 28 days by gavage also resulted in no adverse effects or mortality. No abnormal clinical signs, behavioral changes, body weight changes, or changes in food and water consumption occurred in either study. There were no changes in hematological and serum chemistry values, organ weights, or gross or histological characteristics. Based on test results, it is concluded that ALIBIRD is well tolerated in rats at an acute and subchronic (28 days) dose of 2,000 mg/kg of body weight. PMID:23834798

  2. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... section 3 of TSCA and in 40 CFR Part 792—Good Laboratory Practice Standards apply to this section. The... Biochemistry. (i) Clinical biochemistry determinations to investigate major toxic effects in tissues and... hematological and clinical biochemistry variables before dosing commences. (9) Pathology—(i)Gross necropsy....

  3. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hussin Muhammad

    2012-04-01

    Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  4. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    Science.gov (United States)

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  5. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    Science.gov (United States)

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome. PMID:26525505

  6. Influence of coefficient of variation in determining significant difference of quantitative values obtained from 28-day repeated-dose toxicity studies in rats.

    Science.gov (United States)

    Kobayashi, Katsumi; Sakuratani, Yuki; Abe, Takemaru; Yamazaki, Kazuko; Nishikawa, Satoshi; Yamada, Jun; Hirose, Akihiko; Kamata, Eiichi; Hayashi, Makoto

    2011-01-01

    In order to understand the influence of coefficient of variation (CV) in determining significant difference of quantitative values of 28-day repeated-dose toxicity studies, we examined 59 parameters of 153 studies conducted in accordance with Chemical Substance Control Law in 12 test facilities. Sex difference was observed in 12 parameters and 10 parameters showed large CV in females. The minimum CV was 0.74% for sodium. CV of electrolytes was comparatively small, whereas enzymes had large CV. Large differences in CV were observed for major parameters among 7-8 test facilities. The changes in CV were grossly classified into 11. Our study revealed that a statistical significant difference is usually detected if there is a difference of 7% in mean values between the groups and the groups have a CV of about 7%. A parameter with a CV as high as 30% may be significantly different, if the difference of the mean between the groups is 30%. It would be ideal to use median value to assess the treatment-related effect, rather than mean, when the CV is very high. We recommend using CV of the body weight as a standard to judge the adverse effect level.

  7. 氟氯氰菊酯亚急性吸入毒性实验研究%Inhalation toxicity of cyfluthrin for 28-day repeated dose in rats

    Institute of Scientific and Technical Information of China (English)

    秦珩; 乔善磊; 顾军; 钟义红; 杨洪宝; 王玉邦; 施爱民

    2012-01-01

    Objective To determine the inhalation toxicity and find the non -observed adverse effect level (NOAEL) of cyfluthrin for a 28-day repeated dose in rats. Methods Clean-grade SD rats were randomly divided into 5 groups with 5 females and 5 males in each. The animals inhaled DMSO or cyfluthrin at the concentration of 0, 7. 81 , 9. 05 and 18. 98 mg/m for 4 weeks (6 h/d, 5 d/w). At the end of inhalation , all the animals were kindly sacrificed. Their organs were collected for histopathological examination . Blood samples were collected for analysis of complete blood count , biochemistry and coagulation. Results The animals in 18. 98 mg/m3 group were found scratching repeatedly around the mouth, listless, fidgeting, trembling, discharging blood around the mouth and nose . However, symptoms in females were less serious than in males. Furthermore , the body mass , feed efficiency , weight of kidney of animals in this dose male group were found decreased compared with the control group . Biochemistry detection revealed that serum AST was elevated markedly in both genders of 18. 98 mg/m3 group and in males of 9. 05 mg/m3 group. No obvious abnormity was found in 7.81 mg/m3 group or control group. Conclusion Based on the results above, the non-observed adverse effect level (NOAEL) of cyfluthrin in SD rats is 7. 81 mg/m3 for 28 d repeated inhalation in this study.%目的 观察氟氯氰菊酯染毒大鼠亚急性吸入毒性.方法 7周龄清洁级SD大鼠随机分成5组,每组雌雄各5只,分别吸入氟氯氰菊酯0,7.81,9.05,18.98 mg/m3及溶剂二甲亚砜,每天6 h,每周5 d,共28 d.实验结束时取血液做常规生化指标、血细胞指标、血凝学指标检测.取心、肝、脾等8种主要脏器称重并做病理组织学检查.结果 18.98 mg/m3组动物在染毒中呈现反复抓挠口周、烦躁不安、鼻有血性分泌物、颤抖,染毒结束后呈现萎靡、蜂腰、四肢无力的体征.雌性动物的毒性表现较雄性低.与溶剂对照组相

  8. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster.

    Science.gov (United States)

    Langkilde, Søren; Mandimika, Tafadzwa; Schrøder, Malene; Meyer, Otto; Slob, Wout; Peijnenburg, Ad; Poulsen, Morten

    2009-06-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.

  9. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster

    DEFF Research Database (Denmark)

    Langkilde, Søren; Mandimika, T.; Schrøder, Malene;

    2009-01-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanum tuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine t......Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanum tuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha...

  10. A 28-day repeat dose toxicity study of steroidal glycoalkaloids a-solanine and a-chaconine in the Syrian Golden Hamster

    NARCIS (Netherlands)

    Langkilde, S.; Mandimika, T.; Schroder, M.; Meyer, O.; Slob, W.; Peijnenburg, A.A.C.M.; Poulsen, M.

    2009-01-01

    Glycoalkaloids ¿-solanine and ¿-chaconine are naturally present toxicants in the potato plant (Solanum tuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of ¿-solanine to ¿-chaconine m

  11. Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam – a Siddha preparation on rodents

    OpenAIRE

    Marimuthu Kannadasana; Ganesan Sumathy; Palanivel Thirusangu Sangeetha; Chidambaram Saravanababu; Kathirvelu Baskar

    2016-01-01

    Objective: To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam (KAC) in Sprague Dawley rats of both sexes. Methods: Acute oral toxicity was conducted with 2000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min, 1, 2, 4 and 24 h and for up to 14 days. In repeated 28-day oral toxicity study, the KAC formulation was administered orally with 600, 900 and 1200 mg/k...

  12. Differences in gene expression profiles in the liver between carcinogenic and non-carcinogenic isomers of compounds given to rats in a 28-day repeat-dose toxicity study.

    Science.gov (United States)

    Nakayama, Koji; Kawano, Yukiko; Kawakami, Yuuki; Moriwaki, Norichika; Sekijima, Masaru; Otsuka, Masanori; Yakabe, Yoshikuni; Miyaura, Hideki; Saito, Koichi; Sumida, Kayo; Shirai, Tomoyuki

    2006-12-15

    Some compounds have structural isomers of which one is apparently carcinogenic, and the other not. Because of the similarity of their chemical structures, comparisons of their effects can allow gene expression elicited in response to the basic skeletons of the isomers to be disregarded. We compared the gene expression profiles of male Fischer 344 rats administered by daily oral gavage up to 28 days using an in-house oligo microarray. 2-Acetylaminofluorene (2-AAF), 2,4-diaminotoluene (2,4-DAT), 2-nitropropane (2-NP), and 2-nitro-p-phenylenediamine (2-NpP) are hepatocarcinogenic. However, their isomers, 4-acetylaminofluorene (4-AAF), 2,6-diaminotoluene (2,6-DAT), 1-nitropropane (1-NP), and 4-nitro-o-phenylenediamine (4-NoP), are non-hepatocarcinogenic. Because of the limited carcinogenicity of 2-NpP, we attempted to perform two-parametric comparison analyses with (1) a set of 4 isomers: 2-AAF, 2,4-DAT, 2-NP, and 2-NpP as "carcinogenic", and 4-AAF, 2,6-DAT, 1-NP, and 4-NoP as "non-carcinogenic"; and (2) a set of 3 isomers: 2-AAF, 2,4-DAT, and 2-NP, as "carcinogenic", and 4-AAF, 2,6-DAT, and 1-NP as "non-carcinogenic". After ratio filtering and Welch's approximate t-test analysis, 54 and 28 genes were selected from comparisons between the sets of 3 and 4 isomers, respectively, for day 28 data. Using hierarchical clustering analysis with the 54 or 28 genes, 2-AAF, 2,4-DAT, and 2-NP clustered into a "carcinogenic" branch. 2-NpP was in the same cluster as 4-NoP and 4-AAF. This clustering corresponded to the previous finding that 2-NpP is not carcinogenic in male Fischer 344 rats, which indicates that comparing the differences in gene expression elicited by different isomers is an effective method of developing a prediction system for carcinogenicity. PMID:17070881

  13. 5-Day repeated inhalation and 28-day post-exposure study of graphene.

    Science.gov (United States)

    Shin, Jae Hoon; Han, Sung Gu; Kim, Jin Kwon; Kim, Boo Wook; Hwang, Joo Hwan; Lee, Jong Seong; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il Je

    2015-01-01

    Graphene has recently been attracting increasing attention due to its unique electronic and chemical properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concentration (0.68 ± 0.14 mg/m(3) graphene) and (3) high concentration (3.86 ± 0.94 mg/m(3) graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body weights or organ weights of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was observed in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was observed in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concentrations and time points used in this study.

  14. Genotoxic effects of chromium oxide nanoparticles and microparticles in Wistar rats after 28 days of repeated oral exposure.

    Science.gov (United States)

    Singh, Shailendra Pratap; Chinde, Srinivas; Kamal, Sarika Srinivas Kalyan; Rahman, M F; Mahboob, M; Grover, Paramjit

    2016-02-01

    The nanotechnology industry has advanced rapidly in the last 10 years giving rise to the growth of the nanoparticles (NPs) with great potential in various arenas. However, the same properties that make NPs interesting raise concerns because their toxicity has not been explored. The in vivo toxicology of chromium oxide (Cr2O3)-NPs is not known till date. Therefore, this study investigated the 28-day repeated toxicity after 30, 300 and 1000 mg/kg body weight (bw)/day oral treatment with Cr2O3-NPs and Cr2O3 microparticles (MPs) in Wistar rats. The mean size of Cr2O3-NPs and Cr2O3-MPs was 34.89 ± 2.65 nm and 3.76 ± 3.41 μm, respectively. Genotoxicity was assessed using comet, micronucleus and chromosomal aberration (CA) assays. The results revealed a significant increase in DNA damage in peripheral blood leucocytes and liver, micronuclei and CA in bone marrow after exposure of 300 and 1000 mg/kg doses of Cr2O3-NPs and Cr2O3-MPs only at 1000 mg/kg bw/day. Cr biodistribution was observed in all the tissues in a dose-dependent manner. The maximum amount of Cr was found in the kidneys and least in the brain of the treated rats. More of the Cr was excreted in the faeces than in the urine. Furthermore, nanotreated rats displayed much higher absorption and tissue accumulation. These findings provide initial data of the probable genotoxicity and biodistribution of NPs and MPs of Cr2O3 generated through repeated oral treatment. PMID:26503004

  15. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    OpenAIRE

    Mortensen Alicja; Vogel Ulla; Gao Xueyun; Larsen Agnete; Qvortrup Klaus; Hadrup Niels; Loeschner Katrin; Lam Henrik; Larsen Erik H

    2011-01-01

    Abstract Background The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. Results AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer ...

  16. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Qvortrup, Klaus;

    2011-01-01

    in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of Ag......Background: The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food...... and food contact materials. Results: AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study...

  17. 啮齿类动物28天重复剂量经口毒性改良试验简介与进展%Introduction and progress on the enhancement of repeated dose 28-day oral toxicity study in rodents

    Institute of Scientific and Technical Information of China (English)

    王恒娟; 刘兆平

    2012-01-01

    Repeated dose 28-day oral toxicity study in rodents ( OECD Test Guidelines 407) is widely used to evaluate the general toxicity of chemicals. In 1998, the Organization for Economic Co-operation and Development (OECD) enhanced existing TG 407 to develop new Test Guidelines for screening and testing potential endocrine disruptors. This procedure has been verified by an extensive international validation program. To provide reference for developing endocrine disruptor evaluation system in China, the enhanced TG 407, its progress and its advantages and disadvantages were summarized in this paper.%经济合作与发展组织(Organization for Economic Co-operation and Development,OECD)推荐的啮齿类动物28天重复剂量经口毒性试验( OECD TG 407)是一种广泛用于评价化学物一般毒性的毒理学试验方案.OECD在1998年对其进行改良后,建立TG 407改良试验并经世界多国实验室验证,用于检测化学物的内分泌干扰作用.本文简要介绍了OECD TG 407改良试验指南,并对其进展情况以及优缺点进行综述,以期为我国的内分泌干扰物的评价体系提供参考.

  18. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

    Directory of Open Access Journals (Sweden)

    Mortensen Alicja

    2011-06-01

    Full Text Available Abstract Background The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs and silver acetate (AgAc to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food and food contact materials. Results AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP. The AgNPs remained stable throughout the duration of the 28-day oral toxicity study in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of AgNPs. Besides the intestinal system, the largest silver concentrations were detected in the liver and kidneys. Silver was also found in the lungs and brain. Autometallographic (AMG staining revealed a similar cellular localization of silver in ileum, liver, and kidney tissue in rats exposed to AgNPs or AgAc. Using transmission electron microscopy (TEM, nanosized granules were detected in the ileum of animals exposed to AgNPs or AgAc and were mainly located in the basal lamina of the ileal epithelium and in lysosomes of macrophages within the lamina propria. Using energy dispersive x-ray spectroscopy it was shown that the granules in lysosomes consisted of silver, selenium, and sulfur for both AgNP and AgAc exposed rats. The diameter of the deposited granules was in the same size range as that of the administered AgNPs. No silver granules were detected by TEM in the liver. Conclusions The results of the present study demonstrate that the organ distribution of silver was similar when AgNPs or AgAc were administered orally to rats. The presence of silver

  19. Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2015-09-15

    Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

  20. Repeated-dose liver micronucleus assay: an investigation with 2-nitropropane, a hepatocarcinogen.

    Science.gov (United States)

    Kawakami, Satoru; Araki, Tetsuro; Nakajima, Mikio; Kusuoka, Osamu; Uchida, Keisuke; Sato, Norihiro; Tanabe, Yoko; Takahashi, Kaori; Wako, Yumi; Kawasako, Kazufumi; Tsurui, Kazuyuki

    2015-03-01

    The utility of the repeated-dose liver micronucleus (RDLMN) assay in the detection of a genotoxic hepatocarcinogen was evaluated. In this paper, a rat hepatocarcinogen, 2-nitropropane (2-NP), was administered orally to young adult rats for 14 and 28 days without a partial hepatectomy or a mitogen, and the micronucleus induction in liver was examined using a simple method to isolate hepatocytes. In addition, a bone marrow micronucleus assay was conducted concomitantly. The frequency of micronucleated hepatocytes induced by 2-NP increased significantly in both the 14- and 28-day repeated-dose studies, while the bone marrow micronucleus assays were negative in each study. These results indicate that the RDLMN assay is useful for detecting a genotoxic hepatocarcinogen that is negative in bone marrow micronucleus assays and is a suitable in vivo genotoxicity test method for integration into a repeated-dose general toxicity study. PMID:25892624

  1. Repeated dose 28-day oral toxicity study in Wistar rats with a mixture of five pesticides often found as residues in food: alphacypermethrin, bromopropylate, carbendazim, chlorpyrifos and mancozeb

    DEFF Research Database (Denmark)

    Jacobsen, H.; Østergaard, G.; Lam, Henrik Rye;

    2004-01-01

    -6 female rats, and relative thyroid gland weight was significantly increased in groups 2-6 male rats and of groups 3-6 female rats. Absolute thymus weight of groups 3-6 male and female rats and relative thymus weight of groups 3-6 male rats and groups 3 and 4 female rats was significantly decreased. A mild...... of acetylcholinesterase activity in plasma and brain by chlorpyrifos was not enhanced by coadministration of the other four pesticides. Effects were seen in liver, thyroid, thymus and blood in the combination groups. However, identification of the pesticide(s) responsible for these changes would require further studies...

  2. Biokinetics in repeated-dosing in vitro drug toxicity studies

    NARCIS (Netherlands)

    Kramer, Nynke I; Di Consiglio, Emma; Blaauboer, Bas J; Testai, Emanuela

    2015-01-01

    The aim of the EU FP7 Predict-IV project was to improve the predictivity of in vitro assays for unwanted effects of drugs after repeated dosing. The project assessed the added benefit of integrating long-lived in vitro organotypic cell systems with 'omics' technologies and in silico modelling, inclu

  3. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases.

    Science.gov (United States)

    Heard, Kennon; Bui, Alison; Mlynarchek, Sara L; Green, Jody L; Bond, G Randall; Clark, Richard F; Kozer, Eran; Koff, Raymond S; Dart, Richard C

    2014-01-01

    Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.

  4. Repeated dose of ketamine effect to the rat hippocampus tissue

    Directory of Open Access Journals (Sweden)

    Mehtap Okyay Karaca

    2015-01-01

    Full Text Available Aim: We aimed to determine the neurotoxic effect of repeated ketamine administration on brain tissue and if neurotoxic effect was present, whether this effect continued 16 days later using histological stereological method, a quantitative and objective method. Materials and Methods: Female rats were divided into three groups, each containing five rats. Rats in Group I were given 0.9% saline solution 4 times a day for 5 days. The rats in Groups II and III were given ketamine as intraperitoneal injections. Rats in Groups I and II were sacrificed on 5 th day while the ones in Group III on 21 st day. Cornu ammonis (CA and gyrus dentatus (GD regions in hippocampus tissue of rats were studied using optic fractionation method. Findings: There were significantly less number of cells in hippocampal CA and GD regions of rats from Groups II and III compared to the ones from Group I. Difference in cell number was also significantly higher in Group III than in Group II, but this difference was not as pronounced as the one between Groups III and I. Conclusion: Repeated ketamine doses caused neurotoxicity in rat hippocampus.

  5. In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.

    Science.gov (United States)

    Kim, Jin Sik; Sung, Jae Hyuck; Choi, Byung Gil; Ryu, Hyeon Yeol; Song, Kyung Seuk; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Lee, Gun Ho; Jeon, Kisoo; Ahn, Kang Ho; Yu, Il Je

    2014-03-01

    Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference

  6. The effects of repeated low-dose sarin exposure

    International Nuclear Information System (INIS)

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD5 doses of sarin failed to

  7. The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS)

    NARCIS (Netherlands)

    Tluczkiewicz, I.; Batke, M.; Kroese, D.; Buist, H.; Aldenberg, T.; Pauné, E.; Grimm, H.; Kühne, R.; Schüürmann, G.; Mangelsdorf, I.; Escher, S.E.

    2013-01-01

    In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evalua

  8. Physiological effects following administration of Citrus aurantium for 28 days in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Deborah K., E-mail: deborah.hansen@fda.hhs.gov [Division of Personalized Nutrition and Medicine, U.S. FDA/NCTR, 3900 NCTR Rd., Jefferson, AR 72079 (United States); George, Nysia I. [Division of Personalized Nutrition and Medicine, U.S. FDA/NCTR, 3900 NCTR Rd., Jefferson, AR 72079 (United States); White, Gene E. [Toxicological Pathology Associates, 3900 NCTR Rd., Jefferson, AR 72079 (United States); Pellicore, Linda S. [Office of New Drugs, U.S. FDA/Center for Drug Evaluation and Research, 10903 New Hampshire Ave., Silver Spring, MD 20903 (United States); Abdel-Rahman, Ali; Fabricant, Daniel [Office of Nutrition, Labeling and Dietary Supplements, U.S. FDA/Center for Food Safety and Nutrition, HFS-810, College Park, MD 20740 (United States)

    2012-06-15

    Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

  9. Physiological effects following administration of Citrus aurantium for 28 days in rats

    International Nuclear Information System (INIS)

    Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

  10. Evaluation of the Pharmacokinetic Interaction between Repeated Doses of Rifapentine or Rifampin and a Single Dose of Bedaquiline in Healthy Adult Subjects

    OpenAIRE

    Winter, Helen; Egizi, Erica; Murray, Stephen; Erondu, Ngozi; Ginsberg, Ann; Rouse, Doris J.; Severynse-Stevens, Diana; Pauli, Elliott

    2014-01-01

    This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaq...

  11. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    Science.gov (United States)

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  12. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    Science.gov (United States)

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  13. Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

    NARCIS (Netherlands)

    aan het Rot, Marije; Collins, Katherine A.; Murrough, James W.; Perez, Andrew M.; Reich, David L.; Charney, Dennis S.; Mathew, Sanjay J.

    2010-01-01

    Background: A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days)

  14. The added value of the 90-day repeated dose oral toxicity test for industrial chemicals with a low (sub)acute toxicity profile in a high quality dataset.

    Science.gov (United States)

    Taylor, Katy; Andrew, David J; Rego, Laura

    2014-08-01

    A survey conducted on the EU Notification of New Substances (NONS) database suggested that for industrial chemicals with a profile of low toxicity in (sub)acute toxicity tests there is little added value to the conduct of the 90-day repeated dose study. Avoiding unnecessary animal testing is a central aim of the EU REACH chemicals legislation; therefore we sought to verify the profile using additional data. The OECD's eChemPortal was searched for substances that had both a 28-day and a 90-day study and their robust study summaries were then examined from the ECHA CHEM database. Out of 182 substances with high quality 28-day and 90-day study results, only 18 reported no toxicity of any kind in the (sub)acute tests. However, for 16 of these there were also no reported signs of toxicity at or close to the limit dose (1000mg/kgbw/d) in the 90-day study. Restricting the 'low (sub)acute toxicity in a high quality dataset' profile to general industrial chemicals of no known biological activity, whilst allowing irritant substances, increases the data set and improves the prediction to 95% (20 substances out of 21 substances). The low toxicity profile appears to be of low prevalence within industrial chemicals (10-15%), nevertheless, avoidance of the conduct of a redundant 90-day study for this proportion of the remaining REACH phase-in substances would avoid the use of nearly 50,000 animals and save industry 50million Euros, with no impact on the assessment of human health. PMID:24768988

  15. A GPU implementation of a track-repeating algorithm for proton radiotherapy dose calculations

    CERN Document Server

    Yepes, Pablo P; Taddei, Phillip J

    2010-01-01

    An essential component in proton radiotherapy is the algorithm to calculate the radiation dose to be delivered to the patient. The most common dose algorithms are fast but they are approximate analytical approaches. However their level of accuracy is not always satisfactory, especially for heterogeneous anatomic areas, like the thorax. Monte Carlo techniques provide superior accuracy, however, they often require large computation resources, which render them impractical for routine clinical use. Track-repeating algorithms, for example the Fast Dose Calculator, have shown promise for achieving the accuracy of Monte Carlo simulations for proton radiotherapy dose calculations in a fraction of the computation time. We report on the implementation of the Fast Dose Calculator for proton radiotherapy on a card equipped with graphics processor units (GPU) rather than a central processing unit architecture. This implementation reproduces the full Monte Carlo and CPU-based track-repeating dose calculations within 2%, w...

  16. Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

    Science.gov (United States)

    Tree, Julia A; Hall, Graham; Rees, Peter; Vipond, Julia; Funnell, Simon G P; Roberts, Allen D

    2016-07-01

    Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

  17. Tissue distribution of naringenin conjugated metabolites following repeated dosing of naringin to rats

    OpenAIRE

    Lin, Shiuan-Pey; Hou, Yu-Chi; Tsai, Shang-Yuan; Wang, Meng-Ju; Chao, Pei-Dawn Lee

    2014-01-01

    Background: Naringin is a major antioxidant in Citrus fruits and herbs. To clarify molecular forms distributed to various tissues, we investigated tissue distribution of naringin and relevant metabolites in rats after repeated dosing. Methods: Male Sprague-Dawley rats were orally administered naringin (210 mg/kg) twice daily for eight days. At 6 h post the 17th dose, various tissues including liver, kidney, heart, spleen and brain were collected and analyzed by HPLC method before and after hy...

  18. Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

    Science.gov (United States)

    Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

    2015-10-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects.

  19. Pharmacokinetics and safety of firocoxib after oral administration of repeated consecutive doses to neonatal foals.

    Science.gov (United States)

    Hovanessian, N; Davis, J L; McKenzie, H C; Hodgson, J L; Hodgson, D R; Crisman, M V

    2014-06-01

    The purpose of this study was to determine the pharmacokinetics and safety profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1 mg/kg firocoxib orally q24 h for nine consecutive days, commencing at 36 h of age. Blood was collected for firocoxib analysis using high-pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7, and 8), blood was collected immediately prior to the next dose (24 h trough). Elimination samples (36, 48, 72, 96, 120, and 144 h) were collected after dose 9. Safety was assessed via physical examinations, body weight measurements, gastroscopy, complete blood count, plasma biochemistry and urinalysis. Firocoxib was rapidly absorbed following oral administration with minimal accumulation after repeat dosing. After the final dose, the terminal half-life was approximately 11 h. Firocoxib was below the limit of detection (firocoxib is absorbed in neonatal foals with no demonstrable adverse effects after repeated doses of 0.1 mg/kg. PMID:24749691

  20. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark.

    Directory of Open Access Journals (Sweden)

    Yalena Prado

    2015-02-01

    Full Text Available Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

  1. Statistical methodology to determine kinetically derived maximum tolerated dose in repeat dose toxicity studies.

    Science.gov (United States)

    McFadden, Lisa G; Bartels, Michael J; Rick, David L; Price, Paul S; Fontaine, Donald D; Saghir, Shakil A

    2012-07-01

    Several statistical approaches were evaluated to identify an optimum method for determining a point of nonlinearity (PONL) in toxicokinetic data. (1) A second-order least squares regression model was fit iteratively starting with data from all doses. If the second order term was significant (αmodel was fit iteratively starting with data from all doses except the highest. The mean response for the omitted dose was compared to the 95% prediction interval. If the omitted dose falls outside the confidence interval it is an estimate of the PONL. (3) Slopes of least squares linear regression lines for sections of contiguous doses were compared. Nonlinearity was suggested when slopes of compared sections differed. A total of 33 dose-response datasets were evaluated. For these toxicokinetic data, the best statistical approach was the least squares regression analysis with a second-order term. Changing the α level for the second-order term and weighting the second-order analysis by the inverse of feed consumption were also considered. This technique has been shown to give reproducible identification of nonlinearities in TK datasets.

  2. Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

    Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

  3. Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

    Directory of Open Access Journals (Sweden)

    Roland R Regoes

    2005-08-01

    Full Text Available BACKGROUND: Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses. METHODS AND FINDINGS: Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success. CONCLUSION: Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

  4. Comparison of methionine sources around requirement levels using a methionine efficacy method in 0 to 28 day old broilers.

    Science.gov (United States)

    Agostini, P S; Dalibard, P; Mercier, Y; Van der Aar, P; Van der Klis, J D

    2016-03-01

    The addition of methionine in the poultry feed industry is still facing the relative efficacy dilemma between DL-methionine (DLM) and hydroxy-methionine (HMTBA). The aim of this study was to compare the effect of dietary DLM and HMTBA on broiler performance at different levels of total sulfur amino acids (TSAA). The treatments consisted of a basal diet without methionine addition, and 4 increasing methionine doses for both sources resulting in TSAA/Lysine ratios from 0.62 to 0.73 in the starter phase and 0.59 to 0.82 in the grower phase. The comparison of product performance was performed by three-way ANOVA analysis and by methionine efficacy calculation as an alternative method of comparison. Growth results obtained during the starter phase with the different methionine supplementations did not show significant growth responses to TSAA levels, indicating a lower methionine requirement in the starter phase than currently assumed. However, a significant methionine dose effect was obtained for the period 10 to 28 day of age and for the entire growth period of 0 to 28 day of age. Excepting a significant gender effect, the statistical analysis did not allow for the discrimination of methionine sources, and no interaction between source and dose level was observed up to 28 days of age. A significant interaction between source and dose level was observed for methionine efficacy for the grower phase, and the total growth period showed better HMTBA efficacy at higher TSAA value. The exponential model fitted to each methionine source for body weight response depending on methionine intake or for feed conversion ratio (FCR) depending on methionine doses did not allow the methionine sources to be distinguished. Altogether, these results conclude that methionine sources lead to similar performances response when compared at TSAA values around the broiler requirement level. These results also showed that at TSAA values above requirement, HMTBA had a better methionine efficacy

  5. Inclusion of Safety Pharmacology Endpoints in Repeat-Dose Toxicity Studies.

    Science.gov (United States)

    Redfern, Will S

    2015-01-01

    Whereas pharmacological responses tend to be fairly rapid in onset and are therefore detectable after a single dose, some diminish on repeated dosing, and others increase in magnitude and therefore can be missed or underestimated in single-dose safety pharmacology studies. Safety pharmacology measurements can be incorporated into repeat-dose toxicity studies, either routinely or on an ad hoc basis. Drivers for this are both scientific (see above) and regulatory (e.g. ICH S6, S7, S9). There are inherent challenges in achieving this: the availability of suitable technical and scientific expertise in the test facility, unsuitable laboratory conditions, use of simultaneous (as opposed to staggered) dosing, requirement for toxicokinetic sampling, unsuitability of certain techniques (e.g. use of anaesthesia, surgical implantation, food restriction), equipment availability at close proximity and sensitivity of the methods to detect small, clinically relevant, changes. Nonetheless, 'fit-for-purpose' data can still be acquired without requiring additional animals. Examples include assessment of behaviour, sensorimotor, visual and autonomic functions, ambulatory ECG and blood pressure, echocardiography, respiratory, gastrointestinal, renal and hepatic function. This is entirely achievable if the safety pharmacology measurements are relatively unobtrusive, both with respect to the animals and to the toxicology study itself. Careful pharmacological validation of any methods used, and establishing their detection sensitivity, is vital to ensure the credibility of generated data. PMID:26091647

  6. Proposal of an in silico profiler for categorisation of repeat dose toxicity data of hair dyes.

    Science.gov (United States)

    Nelms, M D; Ates, G; Madden, J C; Vinken, M; Cronin, M T D; Rogiers, V; Enoch, S J

    2015-05-01

    This study outlines the analysis of 94 chemicals with repeat dose toxicity data taken from Scientific Committee on Consumer Safety opinions for commonly used hair dyes in the European Union. Structural similarity was applied to group these chemicals into categories. Subsequent mechanistic analysis suggested that toxicity to mitochondria is potentially a key driver of repeat dose toxicity for chemicals within each of the categories. The mechanistic hypothesis allowed for an in silico profiler consisting of four mechanism-based structural alerts to be proposed. These structural alerts related to a number of important chemical classes such as quinones, anthraquinones, substituted nitrobenzenes and aromatic azos. This in silico profiler is intended for grouping chemicals into mechanism-based categories within the adverse outcome pathway paradigm. PMID:24888375

  7. The Role of Exposure History on HIV Acquisition: Insights from Repeated Low-dose Challenge Studies

    OpenAIRE

    Regoes, Roland R.

    2012-01-01

    To assess the efficacy of HIV vaccine candidates or preventive treatment, many research groups have started to challenge monkeys repeatedly with low doses of the virus. Such challenge data provide a unique opportunity to assess the importance of exposure history for the acquisition of the infection. I developed stochastic models to analyze previously published challenge data. In the mathematical models, I allowed for variation of the animals' susceptibility to infection across challenge repea...

  8. Pharmacokinetics of metadoxine for injection after repeated doses in healthy volunteers

    Institute of Scientific and Technical Information of China (English)

    L(U) Yuan; KANG Zi-sheng; LIU Yan; LI Tian-yun; XIAO Yong-hong

    2007-01-01

    @@ Alcohol-induced liver disease is one of the main epidemic problems nowadays. Metadoxine is a pyridoxine-pyrrolidone carboxylate with significant scavenging property. Metadoxine is able to accelerate the elimination of alcohol from the blood and tissues, help restore the functional structure of the liver and relieve neuro-psychological disorders associated with alcohol intoxication.1-3 The purpose of the study was to assay the pharmacokinetics of domestic metadoxine after repeated doses.

  9. PULMONARY FUNCTION AND PATHOLOGY IN CATS EXPOSED 28 DAYS TO DIESEL EXHAUST

    Science.gov (United States)

    Young adult male cats were exposed 28 days, 20 hours per day, to a 1:14 dilution of diesel exhaust emissions. Following termination of exposure, the following pulmonary function measurements were carried out: lung volumes, maximum expiratory flow rates (MEF), MEF at 50%, 25% and ...

  10. Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound

    Directory of Open Access Journals (Sweden)

    Yang FY

    2012-02-01

    Full Text Available Feng-Yi Yang1, Ming-Che Teng1, Maggie Lu2, Hsiang-Fa Liang2, Yan-Ru Lee1, Chueh-Chuan Yen3, Muh-Lii Liang4,5, Tai-Tong Wong51Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 2Drug Delivery Laboratory, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 3Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, 4Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, 5Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, TaiwanBackground: High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1-conjugated liposomes selectively to brain tumors.Methods: Firefly luciferase (Fluc-labeled human GBM8401 glioma cells were implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin concentration in the treated brains quantified by fluorometer. Growth of the labeled glioma cells was monitored through noninvasive bioluminescence imaging and finally the brain tissue was histologically examined after sacrifice.Results: Compared with the control group, the animals treated with 5 mg/kg injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin followed by repeated pulsed HIFU not only showed significantly enhanced accumulation of drug at the sonicated tumor site but also a significantly elevated tumor-to-normal brain drug

  11. Differential effects of clozapine and pimozide on fixed-ratio responding during repeated dosing.

    Science.gov (United States)

    Wiley, J L; Compton, A D; Porter, J H

    1994-05-01

    Previous research has shown that the differential development of tolerance to the disruption of operant responding produced by repeated dosing with pimozide (PMZ) or clozapine (CLZ) can distinguish these two drugs. In the present study, the effects of PMZ (1 mg/kg) and CLZ (10 mg/kg) on response rate and response duration in rats lever pressing for food reward under a fixed-ratio 30 (FR-30) operant schedule were examined. PMZ suppressed response rates across all 10 days of drug dosing; CLZ produced an initial response rate decrease, with partial recovery (50%) occurring within the 10 day period. Similarly, PMZ produced an increase in response duration that persisted into the postdrug vehicle-injection period, while CLZ did not significantly change response duration. The prolonged suppression of FR responding produced by PMZ is similar to the lack of tolerance to this drug in other types of operant schedules. In contrast, CLZ's effects on response rate are schedule dependent. These results suggest that changes in response duration with repeated dosing may more reliably differentiate typical and atypical neuroleptics than do changes in response rate under FR schedules. PMID:8029297

  12. Tolerability and pharmacokinetics of ebrotidine in healthy subjects given single and repeated oral doses.

    Science.gov (United States)

    Farré, M; Roset, P N; Badenas, J M; Ugena, B; Márquez, M; Albet, C; Herrero, E; Ortiz, J A

    1997-04-01

    The tolerability and safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) and its basic pharmacokinetic parameters were determined after its oral administration to healthy volunteers. Sixteen subjects were selected to participate in two different studies: an increasing single dose study to determine the maximal tolerated dose (from 25 to 1600 mg), and a multiple dose study (stepped doses from 400 to 1600 mg daily for 12 days). The results of the studies showed that ebrotidine has a good tolerability. Vital signs and laboratory tests were not influenced by the study treatment. No clinically relevant adverse effects were reported during the investigation. Ebrotidine reached peak plasma concentrations 2-3 h after oral administration. Its elimination half-life ranged from 9 to 14 h. In conclusion, ebrotidine was well tolerated after administration of oral single doses of up to 1600 mg, and after repeated administration of up to 800 mg/12 h for 12 days.

  13. Acute and 28-Day Subchronic Oral Toxicity of an Ethanol Extract of Zingiber zerumbet (L. Smith in Rodents

    Directory of Open Access Journals (Sweden)

    Chia Ju Chang

    2012-01-01

    Full Text Available The objective of this study was to evaluate the acute and subacute toxicity (28 days of the ethanol extract of Z. zerumbet rhizomes (EEZZ via the oral route in Wistar rats of both sexes. In the acute toxicity study, Wistar rats were administered a single dose of 15 g kg−1 of body weight by gavage, and were monitored for 14 days. EEZZ did not produce any toxic signs or deaths; the 50% lethal dose must be higher than 15 g kg−1. In the subchronic toxicity study, EEZZ was administered by gavage at doses of 1000, 2000 and 3000 mg/kg daily for 4 weeks to Wistar rats. The subacute treatment with EEZZ did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse-effect level for EEZZ is 3000 mg kg−1 for rats under the conditions of this study. Hence, consumption of EEZZ for various medicinal purposes is safe.

  14. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    Science.gov (United States)

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  15. Study of four week repeated dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

    Full Text Available Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56㎎/㎏ body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7

  16. The Role Of Nitric Oxide After Repeated Low Dose Photodynamic Treatments In Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Valentina Rapozzi

    2015-08-01

    Full Text Available Photodynamic therapy (PDT is a clinically approved treatment that causes a selective cytotoxic effect in cancer cells. In addition to the production of singlet oxygen and reactive oxygen species, PDT can induce the release of nitric oxide (NO by up-regulating nitric oxide synthases (NOS. Since non-optimal PDT often causes tumor recurrence, understanding of the molecular pathways involved in the photoprocess is a challenging task for scientists. The present study has examined the response of the PC3 human metastatic prostate cancer cell line, following repeated low-dose pheophorbide a treatments, mimicking non-optimal PDT treatment. The analysis was focused on the NF-kB/YY1/RKIP circuitry as it is (i dysregulated in cancer cells (ii modulated by NO and (iii correlated with the epithelial to mesenchymal transition (EMT. We hypothesized that a repeated treatment of non-optimal PDT induces low levels of NO that lead to cell growth and EMT via regulation of the above circuitry. The expressions of gene products involved in the circuitry and in EMT were analyzed by western blot. The findings demonstrate the cytoprotective role of NO following non-optimal PDT treatments that was corroborated by the use of l-NAME, an inhibitor of NOS.

  17. Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration.

    Science.gov (United States)

    Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

    2014-08-01

    Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.

  18. Haematological and immunological effects of repeated dose exposure of rats to integerrimine N-oxide from Senecio brasiliensis.

    Science.gov (United States)

    Elias, Fabiana; Latorre, Andreia O; Pípole, Fernando; Haraguchi, Mitsue; Górniak, Silvana L; Hueza, Isis M

    2011-09-01

    This study is the first in the literature to focus attention on the possible immunotoxic effect of integerrimine N-oxide content in the butanolic residue (BR) of Senecio brasiliensis, a poisonous hepatotoxic plant that contains pyrrolizidine alkaloids (PAs). PAs have been reported as a pasture and food contaminant and as herbal medicine used worldwide and are responsible for poisoning events in livestock and human beings. After the plant extraction, BR extracted from Senecio brasiliensis was found to contain approximately 70% integerrimine N-oxide by elemental and spectral analyses ((1)H and (13)C NMR), which was administered to adult male Wistar Hannover rats at doses of 3, 6 and 9 mg/kg for 28 days. Body weight gain, food consumption, lymphoid organs, neutrophil analysis, humoural immune response, cellular immune response and lymphocyte analysis were evaluated. Our study showed that integerrimine N-oxide could promote an impairment in the body weight gain, interference with blood cell counts and a reducing T cell proliferative activity in rats; however, no differences in the neutrophil activities, lymphocytes phenotyping and humoural and cellular immune responses were observed. It is concluded that doses of integerrimine N-oxide here employed did not produce marked immunotoxic effects. PMID:21722699

  19. Consuming a multi-ingredient thermogenic supplement for 28 days is apparently safe in healthy adults

    Directory of Open Access Journals (Sweden)

    Roxanne M. Vogel

    2015-07-01

    Full Text Available Background: Thermogenic (TRM supplements are often used by people seeking to decrease body weight. Many TRM supplements are formulated with multiple ingredients purported to increase energy expenditure and maximize fat loss. However, in the past some TRM ingredients have been deemed unsafe and removed from the market. Therefore, it is important to verify the safety of multi-ingredient TRM supplements with chronic consumption. Objective: To assess the safety of daily consumption of a multi-ingredient TRM supplement over a 28-day period in healthy adults. Design: Twenty-three recreationally active adults (11M, 12F; 27.1±5.4 years, 171.6±9.6 cm, 76.8±16.1 kg, 26±5 BMI were randomly assigned either to consume a multi-ingredient TRM supplement (SUP; n=9 or remain unsupplemented (CRL; n=14 for 28 days. Participants maintained their habitual dietary and exercise routines for the duration of the study. Fasting blood samples, resting blood pressure, and heart rate were taken before and after the supplementation period. Samples were analyzed for complete blood counts, comprehensive metabolic, and lipid panels. Results: Significant (p<0.05 group by time interactions were present for diastolic BP, creatinine, estimated glomerular filtration rate (eGFR, chloride, CO2, globulin, albumin:globulin (A/G, and high-density lipoprotein (HDL. Dependent t-tests conducted on significant variables revealed significant (p<0.05 within-group differences in SUP for diastolic BP (+6.2±5.3 mmHG, creatinine (+0.09±0.05 mg/dL, eGFR (−11.2±5.8 mL/min/1.73, globulin (−0.29±0.24 g/dL, A/G (+0.27±0.23, and HDL (−5.0±5.5 mg/dL, and in CRL for CO2 (−1.9±1.5 mmol/L between time points. Each variable remained within the accepted physiological range. Conclusion: Results of the present study support the clinical safety of a multi-ingredient TRM containing caffeine, green tea extract, and cayenne powder. Although there were statistically significant (p<0.05 intragroup

  20. Delayed Reduction of Hippocampal Synaptic Transmission and Spines Following Exposure to Repeated Subclinical Doses of Organophosphorus Pesticide in Adult Mice

    OpenAIRE

    Speed, Haley E.; Blaiss, Cory A.; Kim, Ahleum; Haws, Michael E.; Melvin, Neal R.; Jennings, Michael; Eisch, Amelia J.; Powell, Craig M.

    2011-01-01

    Agricultural and household organophosphorus (OP) pesticides inhibit acetylcholinesterase (AchE), resulting in increased acetylcholine (Ach) in the central nervous system. In adults, acute and prolonged exposure to high doses of AchE inhibitors causes severe, clinically apparent symptoms, followed by lasting memory impairments and cognitive dysfunction. The neurotoxicity of repeated environmental exposure to lower, subclinical doses of OP pesticides in adults is not as well studied. However, r...

  1. Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2011-09-01

    Full Text Available BACKGROUND: Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa. METHODOLOGY/PRINCIPAL FINDINGS: We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling. CONCLUSIONS/SIGNIFICANCE: Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be

  2. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion of...

  3. Evaluation of the pharmacokinetic interaction between repeated doses of rifapentine or rifampin and a single dose of bedaquiline in healthy adult subjects.

    Science.gov (United States)

    Winter, Helen; Egizi, Erica; Murray, Stephen; Erondu, Ngozi; Ginsberg, Ann; Rouse, Doris J; Severynse-Stevens, Diana; Pauli, Elliott

    2015-02-01

    This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin. Coadministration of bedaquiline with rifapentine or rifampin resulted in lower bedaquiline exposures. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the maximum observed concentration (Cmax), area under the concentration-time curve to the last available concentration time point (AUC0-t), and AUC extrapolated to infinity (AUC0-inf) of bedaquiline were 62.19% (53.37 to 72.47), 42.79% (37.77 to 48.49), and 44.52% (40.12 to 49.39), respectively, when coadministered with rifapentine. Similarly, the GMRs and 90% CIs for the Cmax, AUC0-t, and AUC0-inf of bedaquiline were 60.24% (51.96 to 69.84), 41.36% (37.70 to 45.36), and 47.32% (41.49 to 53.97), respectively, when coadministered with rifampin. The Cmax, AUC0-t, and AUC0-inf of M2 were also altered when bedaquiline was coadministered with rifapentine or rifampin. Single doses of bedaquiline, administered alone or with multiple doses of rifapentine or rifampin, were well tolerated, with no safety concerns related to coadministration. Daily administration of rifapentine to patients with tuberculosis presents the same drug interaction challenges as rifampin and other rifamycins. Strong inducers of the cytochrome P450 isoenzyme CYP3A4 should be avoided when considering the use of bedaquiline. (This study is registered at clinicaltrials.gov under identifier NCT02216331

  4. Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats

    International Nuclear Information System (INIS)

    Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day. (author)

  5. Tamarind seed polysaccharide: a 28-day dietary study in Sprague-Dawley rats.

    Science.gov (United States)

    Heimbach, James T; Egawa, Hiroshi; Marone, Palma Ann; Bauter, Mark R; Kennepohl, Elke

    2013-01-01

    Forty male and 40 female Crl:SD® CD® IGS rats were fed diets containing 0, 40,000, 80,000, or 120,000 ppm tamarind seed polysaccharide (equivalent to 3450.8, 6738.9, or 10 597.1 mg/kg bw/day and 3602.1, 7190.1, or 10,690.7 mg/kg bw/day for males and females, respectively) for 28 days. Animals were observed for adverse clinical signs, body weight, feed consumption, hematology and clinical chemistry parameters, urinalysis values were recorded, and at the end of the study the rats underwent a full necropsy. Functional Observational Battery (FOB) and Motor Activity (MA) tests were performed on all animals. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption and food efficiency, FOB or MA findings associated with the administration of tamarind seed polysaccharide. Initial statistically significant decreases in body weight gain and food consumption resolved after the first week and were considered the result of reduced palatability. There were no adverse changes in hematology, coagulation, clinical chemistry or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, estrus cycle, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study and based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for tamarind seed polysaccharide in the diet was the highest concentration tested of 120,000 ppm (equivalent to 10,597 mg/kg bw/day and 10,691 mg/kg bw/day for male and female rats, respectively).

  6. Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats Following 28-day Administration

    Directory of Open Access Journals (Sweden)

    Hiroshi Matsumoto

    2009-11-01

    Full Text Available This study aimed at discriminating carcinogens on the basis of hepatic transcript profiling in the rats administrated with a variety of carcinogens and non-carcinogens. We conducted 28-day toxicity tests in male F344 rats with 47 carcinogens and 26 non- carcinogens, and then investigated periodically the hepatic gene expression profiles using custom microarrays. By hierarchical cluster analysis based on significantly altered genes, carcinogens were clustered into three major groups (Group 1 to 3. The formation of these groups was not affected by the gene sets used as well as the administration period, indicating that the grouping of carcinogens was universal independent of the conditions of both statistical analysis and toxicity testing. Seventeen carcinogens belonging to Group 1 were composed of mainly rat hepatocarcinogens, most of them being mutagenic ones. Group 2 was formed by three subgroups, which were composed of 23 carcinogens exhibiting distinct properties in terms of genotoxicity and target tissues, namely nonmutagenic hepatocarcinogens, and mutagenic and nonmutagenic carcinogens both of which are targeted to other tissues. Group 3 contained 6 carcinogens including 4 estrogenic substances, implying the group of estrogenic carcinogens. Gene network analyses revealed that the significantly altered genes in Group 1 included Bax, Tnfrsf6, Btg2, Mgmt and Abcb1b, suggesting that p53-mediated signaling pathway involved in early pathologic alterations associated with preceding mutagenic carcinogenesis. Thus, the common transcriptional signatures for each group might reflect the early molecular events of carcinogenesis and hence would enable us to identify the biomarker genes, and then to develop a new assay for carcinogenesis prediction.

  7. BEHAVIORAL AND NEUROCHEMICAL CHANGES IN RATS DOSED REPEATEDLY WITH DIISOPROPYLFLUOROPHOSPHATE (DFP)

    Science.gov (United States)

    Behavioral effects of organophosphates (OPs) typically decrease with repeated exposure, despite persistence of OP-induced inhibition of acetylcholinesterase (AChE) and downregulation of muscarinic acetylcholine (ACh) receptors. o characterize this tolerance phenomenon, rats were ...

  8. Toxicogenomic analysis of gene expression changes in rat liver after a 28-day oral benzene exposure

    NARCIS (Netherlands)

    Heijne, W.H.M.; Jonker, D.; Stierum, R.H.; Ommen, van B.; Groten, J.P.

    2005-01-01

    Benzene is an industrial chemical, component of automobile exhaust and cigarette smoke. After hepatic bioactivation benzene induces bone marrow, blood and hepatic toxicity. Using a toxicogenomics approach this study analysed the effects of benzene at three dose levels on gene expression in the liver

  9. Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge

    Directory of Open Access Journals (Sweden)

    Schulze Johannes

    2012-09-01

    Full Text Available Abstract Background Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation. Methods A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days. Pulmonary function and exhaled NO were measured at every visit. Induced sputum was analysed before and after the allergen challenges for cell counts, ECP, IL-5, INF-γ, IL-8, and the transcription factor Foxp3. Results We found a significant decrease in pulmonary function, an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness, as well as a significant induction of eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the majority of patients. Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms. Conclusions Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation. The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations. Trial registration ClinicalTrials.govNCT00677209

  10. The haemotoxicity of azathioprine in repeat dose studies in the female CD-1 mouse.

    Science.gov (United States)

    Molyneux, Gemma; Gibson, Frances M; Chen, Christabelle M; Marway, Harpal K; McKeag, Sean; Mifsud, Charles V J; Pilling, Andrew M; Whayman, Matthew J; Turton, John A

    2008-04-01

    Azathioprine (AZA) is a cytotoxic immunosuppressive drug used in the prevention of rejection in organ transplants and the treatment of auto-immune diseases. However, AZA is haemotoxic causing significant bone marrow depression. The present studies were to characterize the haemotoxicity of AZA in the female CD-1 mouse. In Experiment 1, a dose-ranging study, with AZA gavaged daily for 10 days, clinical evidence of toxicity was evident at 125 mg/kg and above. Experiment 2 was a dose-response study with AZA gavaged daily for 10 days at 40-120 mg/kg. At day 1 after the final dose, AZA induced a dose-related pancytopaenia, reduced femoral marrow cellularity, increases in serum levels of the cytokine fms-like tyrosine kinase 3 ligand, reduction in granulocyte-monocyte colony-forming units and erythroid colonies, and increased bone marrow apoptosis. Histology demonstrated hepatocyte hypertrophy, thymic atrophy, reduced splenic extramedullary haemopoiesis, and reduced cellularity of sternal bone marrow. In Experiment 3, AZA was dosed for 10 days at 100 mg/kg with autopsies at 1, 3, 9, 22, 29, 43 and 57 days postdosing. At 1, 3 and 9 days, haematological parameters reflected changes in Experiment 2. At 22/29 days, many blood parameters were returning towards normal; at 43/57 days, most parameters compared with controls. However, there was some evidence of a persistent (i.e. residual/late-stage) mild reduction in RBC and erythroid progenitor cell counts at day 43/57. We conclude that the CD-1 mouse provides an acceptable model for the haemotoxicity of AZA in man.

  11. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    Energy Technology Data Exchange (ETDEWEB)

    Akane, Hirotoshi [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Saito, Fumiyo [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Shiraki, Ayako [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Takeyoshi, Masahiro; Imatanaka, Nobuya [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Itahashi, Megu [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Murakami, Tomoaki [Laboratory of Veterinary Toxicology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2014-09-01

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc{sup +} neurons at 1000 ppm and Fos{sup +} neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. - Highlights: • Neuronal toxicity parameters after 28-day glycidol treatment were examined in rats. • Region-specific global gene expression profiling was conducted in brain regions. • Cortical tissues downregulated genes on axonogenesis and synaptic transmission. • Cortical tissues

  12. Consecutive thrombelastography clot strength profiles in patients with severe sepsis and their association with 28-day mortality

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Windeløv, Nis A; Ibsen, Michael;

    2013-01-01

    sepsis admitted to the intensive care unit (ICU). Clinical scores/variables, infection, TEG, biochemistry, therapy, and overall mortality were recorded. RESULTS: Fifty patients (60% men, median age 62 years, 28-day mortality 24%) were included. At admission, 22%, 48%, and 30% had a hypocoagulable...... odds ratio, 4.29 [95% confidence interval, 1.35-13.65], P = .014). In hypocoagulable and hypercoagulable patients, only fibrinogen (P = .041 and P platelets (P

  13. Downregulation of immediate-early genes linking to suppression of neuronal plasticity in rats after 28-day exposure to glycidol

    International Nuclear Information System (INIS)

    We previously found that the 28-day oral toxicity study of glycidol at 200 mg/kg/day in rats resulted in axonopathy in both the central and peripheral nervous systems and aberrations in the late-stage of hippocampal neurogenesis targeting the process of neurite extension. To capture the neuronal parameters in response to glycidol toxicity, these animals were subjected to region-specific global gene expression profiling in four regions of cerebral and cerebellar architectures, followed by immunohistochemical analysis of selected gene products. Expression changes of genes related to axonogenesis and synaptic transmission were observed in the hippocampal dentate gyrus, cingulate cortex and cerebellar vermis at 200 mg/kg showing downregulation in most genes. In the corpus callosum, genes related to growth, survival and functions of glial cells fluctuated their expression. Immunohistochemically, neurons expressing gene products of immediate-early genes, i.e., Arc, Fos and Jun, decreased in their number in the dentate granule cell layer, cingulate cortex and cerebellar vermis. We also applied immunohistochemical analysis in rat offspring after developmental exposure to glycidol through maternal drinking water. The results revealed increases of Arc+ neurons at 1000 ppm and Fos+ neurons at ≥ 300 ppm in the dentate granule cell layer of offspring only at the adult stage. These results suggest that glycidol suppressed neuronal plasticity in the brain after 28-day exposure to young adult animals, in contrast to the operation of restoration mechanism to increase neuronal plasticity at the adult stage in response to aberrations in neurogenesis after developmental exposure. - Highlights: • Neuronal toxicity parameters after 28-day glycidol treatment were examined in rats. • Region-specific global gene expression profiling was conducted in brain regions. • Cortical tissues downregulated genes on axonogenesis and synaptic transmission. • Cortical tissues decreased

  14. Successful repeated treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP

    OpenAIRE

    Axelson, Hans W.; Öberg, Gunnar; Askmark, Håkan

    2009-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterised by the occurrence of symmetrical weakness and sensory impairment in arms and legs. The course is relapsing or chronic and progressing. CIDP is considered to be an autoimmune disease, which is supported by the beneficial response to immunomodulating therapies in most patients. We report on a patient with CIDP who has been in remission for more than 3 years after treatment with high dose cyclophosphamide and autologous bl...

  15. Repeated Administration of High-Dose Intermittent Rifapentine Reduces Rifapentine and Moxifloxacin Plasma Concentrations▿

    OpenAIRE

    Dooley, Kelly; Flexner, Charles; Hackman, Judith; Peloquin, Charles A.; Nuermberger, Eric; Chaisson, Richard E.; Dorman, Susan E.

    2008-01-01

    Moxifloxacin- and rifapentine-based regimens are under investigation for the treatment of tuberculosis. However, rifapentine may induce enzymes that metabolize moxifloxacin, resulting in decreased moxifloxacin concentrations. In this phase I, two-period, sequential-design study, 13 subjects received 400 mg moxifloxacin daily for 4 days followed by daily moxifloxacin coadministered with 900 mg rifapentine thrice weekly. Pharmacokinetic analyses were performed after the 4th and 19th doses of mo...

  16. Memory and mood during the night and in the morning after repeated evening doses of MDMA.

    Science.gov (United States)

    Kuypers, K P C; Wingen, M; Ramaekers, J G

    2008-11-01

    Previously it has been shown that MDMA causes memory impairment during daytime testing. However, MDMA is usually taken in the evening or during the night. In addition, it is known that sleep deprivation also causes memory impairment. The present study aimed to assess whether evening doses of MDMA added to, or interacted with the memory impairment due to sleep deprivation. Fourteen healthy subjects participated in a double-blind, placebo-controlled, two-way cross-over study. Treatments consisted of MDMA 75 and 50 mg divided over the evening or double placebo. Memory tests and subjective measures of mood were conducted at baseline and three times post dosing that is at 6.30 pm, 9.30 pm, 1.30 am and 7 am, respectively -1.5, 1.5, 5.5 and 11 h relative to drug intake (first dose). Memory performance detoriated progessively over time as a function of sleep loss, independent of treatment. MDMA added to this impairment as indicated by a significant main effect of MDMA on verbal and spatial memory performance. Mood ratings and response speed revealed an MDMA by Time interaction. After administration of MDMA response speed improved and feelings of vigor, friendliness, elation, anxiety, confusion, arousal and positive mood increased in magnitude during the night, while all these parameters returned to placebo-like levels on the final morning session. It is concluded that evening doses of MDMA selectively impair memory performance, and that this impairment is additional to the effect of sleep deprivation on memory performance.

  17. The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

    Science.gov (United States)

    Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

    2013-01-01

    The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. PMID:27481023

  18. Repeated exposure to an ambient level of NO{sub 2} enhances asthmatic response to a nonsymptomatic allergen dose

    Energy Technology Data Exchange (ETDEWEB)

    Strand, V. [The Institute of Environmental Medicine at the Karolinska Institute, Stockholm (Sweden); Svartengren, M. [Huddinge Univ. Hospital, Dept. of Occupational Medicine, Stockholm (Sweden); Rak, S. [Sahlgrenska Univ. Hospital, Allergy Center, Gothenburg (Sweden); Barck, C.; Bylin, G. [Huddinge Univ. Hospital, Dept. of Respiratory and Allergic Diseases, and the Institute of Medicine at the Karolinska Inst., Stockholm (Sweden)

    1998-06-01

    We investigated the effects of NO{sub 2} and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 {mu}g x m{sup -3} NO{sub 2} for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO{sub 2} and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO{sub 2} was at EP-2.5% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO{sub 2} exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO{sub 2} plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO{sub 2} enhances the airway response to a nonsymptomatic allergen dose. (au) 28 refs.

  19. A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose toxicity studies

    International Nuclear Information System (INIS)

    A recent regulatory document for immunotoxicity testing of new pharmaceutical drugs includes cytotoxic natural killer (NK)-cell function as a required parameter in repeated dose toxicity studies. The classical 51Cr-release assay is the conventional test for cytotoxicity testing but several drawbacks with this assay has increased the demand for new reliable test systems. Here, we describe the optimisation of a flow-cytometric cytotoxicity assay especially adapted for regulatory rat studies in drug development. The test principle is based on target cell labelling with 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE) and subsequent DNA-labelling with propidium iodide (PI) for identification of target cells with compromised cell membranes. The results are expressed as percentage of dead targets on a cell-to-cell basis. The final format of the assay includes 0.5 ml peripheral blood, 1.25x105 effector cells per sample, and collection of 500 target events by flow-cytometry. When NKR-P1+ cells were removed from the effector cell population by magnetic depletion the relative proportion decreased from 6 to 0.08%. The corresponding cytotoxic activity decreased from 68 to 8%. Also, the cytotoxic activity showed a significant and positive correlation with the proportion of NK-cells present in the effector cell suspension. Thus, the cytotoxicity measured is almost exclusively exerted by NK-cells. The current flow-cytometric test benefits from using peripheral blood as a source for effector cells since it will not conflict with the use of spleen for histopathological investigations in repeated dose toxicity studies. Additionally, since only a minimal number of effector cells are required per sample repeated testing of the same animal is enabled

  20. Intra-tumor distribution of PEGylated liposome upon repeated injection: No possession by prior dose.

    Science.gov (United States)

    Nakamura, Hiroyuki; Abu Lila, Amr S; Nishio, Miho; Tanaka, Masao; Ando, Hidenori; Kiwada, Hiroshi; Ishida, Tatsuhiro

    2015-12-28

    Liposomes have proven to be a viable means for the delivery of chemotherapeutic agents to solid tumors. However, significant variability has been detected in their intra-tumor accumulation and distribution, resulting in compromised therapeutic outcomes. We recently examined the intra-tumor accumulation and distribution of weekly sequentially administered oxaliplatin (l-OHP)-containing PEGylated liposomes. In that study, the first and second doses of l-OHP-containing PEGylated liposomes were distributed diversely and broadly within tumor tissues, resulting in a potent anti-tumor efficacy. However, little is known about the mechanism underlying such a diverse and broad liposome distribution. Therefore, in the present study, we investigated the influence of dosage interval on the intra-tumor accumulation and distribution of "empty" PEGylated liposomes. Intra-tumor distribution of sequentially administered "empty" PEGylated liposomes was altered in a dosing interval-dependent manner. In addition, the intra-tumor distribution pattern was closely related to the chronological alteration of tumor blood flow as well as vascular permeability in the growing tumor tissue. These results suggest that the sequential administrations of PEGylated liposomes in well-spaced intervals might allow the distribution to different areas and enhance the total bulk accumulation within tumor tissue, resulting in better therapeutic efficacy of the encapsulated payload. This study may provide useful information for a better design of therapeutic regimens involving multiple administrations of nanocarrier drug delivery systems.

  1. Lack of histological cerebellar changes in Wistar rats given pulegone for 28 days. Comparison of immersion and perfusion tissue fixation

    DEFF Research Database (Denmark)

    Mølck, Anne-Marie; Poulsen, Morten; Lauridsen, Søren Tindgard;

    1998-01-01

    Pulegone was given orally by gavage to groups of 28 SPF Wistar rats at dosage levels of 0 or 160 mg/kg body weight per day for 28 days. Clinically treated animals showed slackness, depression, decreased food consumption, and body weight. The loss of body weight was accompanied by a marked decrease...... in plasma creatinine. In contrast to earlier results, this study did not reveal occurrence of cyst-like spaces in the white matter of cerebellum using either perfusion or immersion tissue fixation techniques. Pulegone increased plasma alkaline phosphatase and relative liver weight indicating an adverse...

  2. Combined repeated dose and reproductive/developmental toxicity screening test of 4-methoxy-2-nitroaniline in rats.

    Science.gov (United States)

    Tsubokura, Yasuhiro; Aso, Sunao; Koga, Takayuki; Kikuchi, Junichi; Kobayashi, Toshio; Hoshuyama, Satsuki; Oshima, Yutaka; Miyata, Katsumi; Kusune, Yuji; Muroi, Takako; Yoshida, Tomohiko; Hasegawa, Ryuichi; Ajimi, Shozo; Furukawa, Kotaro

    2015-10-01

    4-Methoxy-2-nitroaniline (4M2NA) is widely used as an intermediate for the synthesis of dyes, pigments and other chemical compounds. Since 4M2NA has amino-group and nitro-group on the benzene ring, it was expected that it induced obvious hemolytic anemia. We conducted a combined repeated dose and reproductive/developmental toxicity screening test according to Organisation for Economic Co-operation and Development (OECD) Test Guideline No. 422 (OECD TG 422) to enrich the toxic information and ensure the safety of 4M2NA. 4M2NA was administered to Crl:CD(SD) male and female rats by gavage at 0, 12.5, 75 or 450 mg/kg/day for 42 to maximum of 54 days through pre-mating, mating, pregnancy and lactation periods. An extramedullary hematopoiesis and congestion in spleen, and higher reticulocyte ratio were noted in only females at 450 mg/kg/day without decreased anemic parameters in the hematological examination. Hypertrophy of centrilobular hepatocytes in both sexes was observed with increased relative liver weight at 450 mg/kg/day. Furthermore, the diffuse follicular cell hypertrophy of the thyroid was observed in females at 450 mg/kg/day. No abnormalities were detected in the reproductive indices of copulation, delivery or fetal viability. We concluded the no-observed-adverse-effect level (NOAEL) for repeated-dose toxicity was 75 mg/kg/day based on the trace evidences of hemolytic anemia, and the NOAEL for reproductive/developmental toxicity as 450 mg/kg/day based on no toxicological concerns for reproductive endpoints. The hemolytic anemia was much milder than expected. Thus, we discussed the reason of this much less hemolytic effect from the point of view of the structural characteristics of 4M2NA. PMID:25367778

  3. Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study

    Science.gov (United States)

    Kura, Aminu Umar; Cheah, Pike-See; Hussein, Mohd Zobir; Hassan, Zurina; Tengku Azmi, Tengku Ibrahim; Hussein, Nor Fuzina; Fakurazi, Sharida

    2014-05-01

    Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant ( p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant ( p brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

  4. Absence of adverse effects of sodium metabisulphite in manufactured biscuits: results of subacute (28-days) and subchronic (85-days) feeding studies in rats.

    Science.gov (United States)

    Ribera, D; Jonker, D; Narbonne, J F; O'Brien, J; Antignac, E

    2001-02-01

    Sulphites are extensively used in the food and drinks industry. Their toxicity has been previously evaluated by addition to the diet or drinking water of laboratory animals. Because interactions between sulphites and food constituents occur, the present work was conducted to determine the subacute and subchronic toxicity of sulphite-bound compounds in a finished product: manufactured biscuits. The studies were performed on Sprague Dawley, rats for 28 and 85 days of dietary exposure. Diets were prepared from sulphited or untreated (controls) biscuits with the addition of sugar, protein, vitamins and minerals according to the nutritional requirements of the animals. Groups of 10 male and 10 female rats were administered diets containing sulphited biscuits at levels of 0, 10, 35 and 75%, corresponding to 10-15, 35-45, 150-170 and 310-340 mg SO2/kg diet. In both studies, no death or clinical abnormalities were reported. Growth rate, food consumption and food conversion efficiency were not affected by treatment. No dose-related changes were observed for haematology, clinical chemistry, ocular examination, renal-function, urinalysis, organ weights or gross and microscopic examinations. The liver concentrations of vitamins A, B1, C and E were not significantly changed except for an increase in vitamin E in high-dose males after 28 days' exposure. Based on these data, the no-observed-adverse-effect level (NOAEL) of sulphites in baked biscuits was judged to be 310 mg SO2/kg diet or 25 mg/kg body weight/day.

  5. Study of four weeks repeated-dose toxic test of Sweet Bee Venom in rats Original Articles

    Directory of Open Access Journals (Sweden)

    Kwon Hae-Yon

    2011-03-01

    Full Text Available Objectives: This study was performed to analyse four weeks repeated -dose toxicity of Sweet Bee Venom (SBV-pure melittin, the major component of honey bee venom in rats. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLPat Biotoxtech Company, a non-clinical study authorized institution. Male and female rats of 5 weeks old were chosen for the pilot study of four weeks repeated-dose toxicity and was injected at the level of 0.56 mg/kg body weight (eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14 mg/kg as midium and low dosage, respectively. Equal amount of normal saline was injected as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups appealed pain sense in the treating time compared to the control group, and side effects such as hyperemia and movement disorder were observed around the area of injection in all experiment groups, and the higher dosage in treatment, the higher occurrence in side effects. 3. Concerning weight measurement, neither male nor female groups showed significant changes compared to the control group. 4. Concerning to the CBC and biochemistry, all experiment groups didn't show any significant changes compared to the control group. 5. Concerning weight measurement of organs, experiment groups didn't show any significant changes compared to the control group. 6. To verify abnormalities of organs and tissues, those such as cerebellum, cerebrum, liver, lung, kidney,and spinal cords were removed and we conducted histologocal observation with H-E staining.Concerning the histologocal observation of liver tissues, some fatty changes were observed around portal vein in 0.56 mg/kg experiment group. But another organs were not detected in any abnormalities. 7. The proper high dosage of SBV for the thirteen weeks repeated test in rats may be 0.28 mg

  6. Defining upper gastrointestinal bleeding from linked primary and secondary care data and the effect on occurrence and 28 day mortality

    Directory of Open Access Journals (Sweden)

    Crooks Colin

    2012-11-01

    Full Text Available Abstract Background Primary care records from the UK have frequently been used to identify episodes of upper gastrointestinal bleeding in studies of drug toxicity because of their comprehensive population coverage and longitudinal recording of prescriptions and diagnoses. Recent linkage within England of primary and secondary care data has augmented this data but the timing and coding of concurrent events, and how the definition of events in linked data effects occurrence and 28 day mortality is not known. Methods We used the recently linked English Hospital Episodes Statistics and General Practice Research Database, 1997–2010, to define events by; a specific upper gastrointestinal bleed code in either dataset, a specific bleed code in both datasets, or a less specific but plausible code from the linked dataset. Results This approach resulted in 81% of secondary care defined bleeds having a corresponding plausible code within 2 months in primary care. However only 62% of primary care defined bleeds had a corresponding plausible HES admission within 2 months. The more restrictive and specific case definitions excluded severe events and almost halved the 28 day case fatality when compared to broader and more sensitive definitions. Conclusions Restrictive definitions of gastrointestinal bleeding in linked datasets fail to capture the full heterogeneity in coding possible following complex clinical events. Conversely too broad a definition in primary care introduces events not severe enough to warrant hospital admission. Ignoring these issues may unwittingly introduce selection bias into a study’s results.

  7. Inhibition of prolactin with bromocriptine for 28days increases blood-brain barrier permeability in the rat.

    Science.gov (United States)

    Rosas-Hernandez, H; Ramirez, M; Ramirez-Lee, M A; Ali, S F; Gonzalez, C

    2015-08-20

    The blood-brain barrier (BBB) is necessary for the proper function of the brain. Its maintenance is regulated by endogenous factors. Recent evidences suggest prolactin (PRL) regulates the BBB properties in vitro, nevertheless no evidence of these effects have been reported in vivo. The aim of this study was to evaluate the role of PRL in the maintenance of the BBB in the rat. Male Wistar rats were treated with Bromocriptine (Bromo) to inhibit PRL production for 28days in the absence or presence of lipopolysaccharide (LPS). BBB permeability was evaluated through the Evans Blue dye and fluorescein-dextran extravasation as well as through edema formation. The expression of claudin-5, occludin, glial fibrillary acidic protein (GFAP) and the PRL receptor (PRLR) was evaluated through western blot. Bromo reduced the physiological levels of PRL at 28days. At the same time, Bromo increased BBB permeability and edema formation associated with a decrement in claudin-5 and occludin and potentiated the increase in BBB permeability induced by LPS. However, no neuroinflammation was detected, since the expression of GFAP was unchanged, as well as the expression of the PRLR. These data provide the first evidence that inhibition of PRL with Bromo affects the maintenance of the BBB through modulating the expression of tight junction proteins in vivo.

  8. Optimization of Hyalella azteca IQ Toxicity Test{trademark} for prediction of 28-day sediment toxicity tests

    Energy Technology Data Exchange (ETDEWEB)

    Novotny, A.N.; Ezzard, C.L.; Douglas, W.S.; Home, M.T. [Aqua Survey, Inc., Flemington, NJ (United States)

    1995-12-31

    The IQ Toxicity Test, which is a rapid screening toxicity test consisting of the observation of in-vivo inhibition of an enzymatic process using a fluorescent substrate, has proven successful for the determination of 24 and 48-hour EC50`s of D. magna, C. dubia, D. pulex and M. bahia. The application of this concept to utilize the freshwater amphipod Hyalella azteca may be an excellent way in which to reduce the standard 28-day chronic sediment toxicity test to possibly one hour`s time. This study incorporates an additive experimental design to explore the effects of and interactions between five specific variables: size of the amphipod, exposure time to the toxicant, concentration of substrate, exposure time to the substrate, and length of time starved prior to testing. The results of the IQ toxicity test were compared to those of a 28-day chronic sediment toxicity test. Preliminary data indicate that there is an optimal combination of these variables which results in a concise, reproducible toxicity test for use with Hyalella azteca, and would potentially be applicable to other freshwater amphipods in the future.

  9. A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

    Directory of Open Access Journals (Sweden)

    Michelle R Newman

    Full Text Available The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1, B1 and Intracisternal-A-Particle (IAP repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17-19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen and a tissue fundamental to the aging process (liver. Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA

  10. Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

    Directory of Open Access Journals (Sweden)

    Wust Peter

    2010-05-01

    Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

  11. Comparison in the calculation of committed effective dose using the ICRP 30 and ICRP 60 models for a repeated incorporation by inhalation of I-125

    International Nuclear Information System (INIS)

    Presently work, a comparison in the calculation of committed effective dose using the models of the ICRP 30 and those of the ICRP 60 for the analysis of internal dose due to repeated incorporation of I-125 is shown. The estimations of incorporated activity are obtained starting from the proportionate data for an exercise of inter comparison, with which it should be determined the internal dose later on. For to estimate the initial activity incorporated by repeated dose was assumed that this it was given through of multiple individual incorporations which happened in the middle points of the monitoring periods. The results using the models of the ICRP 30 and of the ICRP 60 are compared and the causes of the differences are analyzed. (Author)

  12. Upregulation of nucleoside triphosphate diphosphohydrolase-1 and ecto-5'-nucleotidase in rat hippocampus after repeated low-dose dexamethasone administration.

    Science.gov (United States)

    Drakulić, Dunja; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana; Veličković, Nataša; Guševac, Ivana; Mitrović, Nataša; Buzadžić, Ivana; Horvat, Anica

    2015-04-01

    Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5'-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.

  13. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

    2009-01-15

    Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe{sub 2}O{sub 3} nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 {mu}g) intranasal exposure of nano- and submicron-sized Fe{sub 2}O{sub 3} particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe{sub 2}O{sub 3} particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe{sub 2}O{sub 3} particle treatment (p < 0.05). The nano-sized Fe{sub 2}O{sub 3} generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe{sub 2}O{sub 3} particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe{sub 2}O{sub 3} treatment. In contrast, in the submicron-sized Fe{sub 2}O{sub 3} treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe{sub 2}O{sub 3} nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the

  14. Effectiveness of Percutaneous Coronary Intervention within 12 Hours to 28 Days of ST-Elevation Myocardial Infarction in a Real-World Chinese Population

    OpenAIRE

    Xingli Wu; Dingyou Yang; Yusheng Zhao; Caiyi Lu; Yu Wang

    2013-01-01

    OBJECTIVES: Percutaneous coronary intervention( PCI) for ST-elevation myocardial infarction (STEMI) has been widely accepted for patient who come within 12 hours, but for those who come to the hospital late (12 hours to 28 days) the long-term data and possible predictors are limited regarding 'hard' endpoints in 'real world'. METHODS: The registry data of all 5523 consecutive patients admitted due to an incident STEMI (12 hours to 28 days) in our center were analyzed. Patients were divided in...

  15. Modeling in-Hospital Patient Survival During the First 28 Days After Intensive Care Unit Admission: a Prognostic Model for Clinical Trials in General Critically Ill Patients

    OpenAIRE

    Moreno, R; Metnitz, P; Metnitz, B; Bauer, P.; Afonso de Carvalho, S; Hoechtl, A; SAPS 3 Investigators

    2008-01-01

    OBJECTIVE: The objective of the study was to develop a model for estimating patient 28-day in-hospital mortality using 2 different statistical approaches. DESIGN: The study was designed to develop an outcome prediction model for 28-day in-hospital mortality using (a) logistic regression with random effects and (b) a multilevel Cox proportional hazards model. SETTING: The study involved 305 intensive care units (ICUs) from the basic Simplified Acute Physiology Score (SAPS) 3 cohort. ...

  16. Intakes of culinary herbs and spices from a food frequency questionnaire evaluated against 28-days estimated records

    Directory of Open Access Journals (Sweden)

    Blomhoff Rune

    2011-05-01

    Full Text Available Abstract Background Worldwide, herbs and spices are much used food flavourings. However, little data exist regarding actual dietary intake of culinary herbs and spices. We developed a food frequency questionnaire (FFQ for the assessment of habitual diet the preceding year, with focus on phytochemical rich food, including herbs and spices. The aim of the present study was to evaluate the intakes of herbs and spices from the FFQ with estimates of intake from another dietary assessment method. Thus we compared the intake estimates from the FFQ with 28 days of estimated records of herb and spice consumption as a reference method. Methods The evaluation study was conducted among 146 free living adults, who filled in the FFQ and 2-4 weeks later carried out 28 days recording of herb and spice consumption. The FFQ included a section with questions about 27 individual culinary herbs and spices, while the records were open ended records for recording of herbs and spice consumption exclusively. Results Our study showed that the FFQ obtained slightly higher estimates of total intake of herbs and spices than the total intake assessed by the Herbs and Spice Records (HSR. The correlation between the two assessment methods with regard to total intake was good (r = 0.5, and the cross-classification suggests that the FFQ may be used to classify subjects according to total herb and spice intake. For the 8 most frequently consumed individual herbs and spices, the FFQ obtained good estimates of median frequency of intake for 2 herbs/spices, while good estimates of portion sizes were obtained for 4 out of 8 herbs/spices. Conclusions Our results suggested that the FFQ was able to give good estimates of frequency of intake and portion sizes on group level for several of the most frequently used herbs and spices. The FFQ was only able to fairly rank subjects according to frequency of intake of the 8 most frequently consumed herbs and spices. Other studies are warranted

  17. Nutrition Composition and Single, 14-Day and 13-Week Repeated Oral Dose Toxicity Studies of the Leaves and Stems of Rubus coreanus Miquel.

    Science.gov (United States)

    Om, Ae-Son; Song, Yu-Na; Noh, GeonMin; Kim, HaengRan; Choe, JeongSook

    2016-01-01

    The leaves and stems of the plant Rubus coreanus Miquel (RCMLS) are rich in vitamins, minerals and phytochemicals which have antioxidant, anti-hemolytic, anti-inflammatory, anti-fatigue and anti-cancer effects. However, RCMLS is not included in the Korean Food Standards Codex due to the lack of safety assurance concerning RCMLS. We evaluated single and repeated oral dose toxicity of RCMLS in Sprague-Dawley rats. RCMLS did not induce any significant toxicological changes in both male and female rats at a single doses of 2500 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects in clinical signs, body weight, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at doses of 625, 1250, and 2500 mg/kg/day. The LD50 and LOAEL of RCMLS might be over 2500 mg/kg body weight/day and no target organs were identified. Therefore, this study revealed that single and repeated oral doses of RCMLS are safe. PMID:26760987

  18. Psychomotor performance during a 28 day head-down tilt with and without lower body negative pressure

    Science.gov (United States)

    Traon, A. Pavy-le; de Feneyrols, A. Rous; Cornac, A.; Abdeseelam, R.; N'uygen, D.; Lazerges, M.; Güell, A.; Bes, A.

    Several factors may affect psychomotor performance in space: sensory-motor changes, sleep disturbances, psychological modifications induced by the social isolation and confinement. However, psychomotor performance is difficult to assess. A battery of standardized and computerized tests, so-called "Automated Portable Test System" (APTS) was devised to ascertain the cognitive, perceptive and motor abilities and their possible fluctuations according to environmental effects. Antiorthostatic bedrest, often used to simulate weightlessness, (particularly cardiovascular modifications) also constitutes a situation of social confinement and isolation. During two bedrest experiments (with head-down tilt of -6°) of 28 days each, we intended to assess psychomotor performance of 6 males so as to determine whether: —on the one hand, it could be altered by remaining in decubitus; —on the other, the Lower Body Negative Pressure sessions, designed to prevent orthostatic intolerance back on Earth, could improve the performance. To accomplish this, part of the APTS tests as well as an automated perceptive attention test were performed. No downgrading of psychomotor performance was observed. On the contrary, the tasks were more accurately performed over time. In order to assess the experimental conditions on the acquisition phase, the learning curves were modelled. A beneficial effect of the LBNP sessions on simple tests involving the visual-motor coordination and attention faculties can only be regarded as a mere trend. Methods used in this experiment are also discussed.

  19. Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats.

    Science.gov (United States)

    Cariddi, L N; Escobar, F M; Sabini, M C; Campra, N A; Bagnis, G; Decote-Ricardo, D; Freire-de-Lima, C G; Mañas, F; Sabini, L I; Dalcero, A M

    2016-04-01

    The present study aimed to characterize the chlorogenic acid (ChlA) capacity to reverse the toxic effects induced by ochratoxin A (OTA) in a subacute toxicity test in rats. Male Wistar rats were fed orally by gavage for 28 days with OTA (0.4mg/kg bw/day), ChlA (5mg/kg bw/day) or the combination OTA (0.4mg/kg bw/day)+ChlA (5mg/kg bw/day). No deaths, no decrease in feed intake or body weight in any experimental group were recorded. The negative control group and the animals treated with ChlA alone showed no changes in any parameters evaluated. In OTA-treated group significant changes such as decrease in urine volume, proteinuria, occult blood, increase in serum creatinine values; decrease in absolute and relative kidney weight and characteristics histopathological lesions that indicated kidney damage were observed. However, limited effect on oxidative stress parameters were detected in kidneys of OTA-treated group. Animals treated with the combination OTA+ChlA were showed as negative control group in the evaluation of several parameters of toxicity. In conclusion, ChlA, at given concentration, improved biochemical parameters altered in urine and serum and pathological damages in kidneys induced by OTA exposure, showing a good protective activity, but not by an apparent antioxidant mechanism. PMID:26987112

  20. Toxicological assessment of β-(1-->6)-glucan (lasiodiplodan) in mice during a 28-day feeding study by gavage.

    Science.gov (United States)

    Túrmina, Janaína A; Carraro, Emerson; Alves da Cunha, Mário A; Dekker, Robert F H; Barbosa, Aneli M; Dos Santos, Fábio Seidel; Silva, Luiz A; Malfatti, Carlos R M

    2012-01-01

    Studies evaluating the toxicity caused by fungal exopolysaccharides of the β-(1-->6)-D-glucan type are rare. In this study, the toxicological effects of sub-chronic treatments with lasiodiplodan (β-(1-->6)-D-glucan from Lasiodiplodia theobromae MMPI) were evaluated in mice through the assessment of biochemical, hematological, and histopathological alterations. Thirty-two mice (16 male, 16 female) were used in this study divided in two groups; one group received lasiodiplodan (50 mg/kg body weight) daily for 28 days via gavage, and another (control group) received saline during the same period. Blood samples were collected via cardiac puncture for hematological and biochemical analyses. Liver, heart, kidney, and spleen were collected for histopathological analysis. Statistical analysis was performed through one-way analysis of variance and only p < 0.05 F-values were presented. Significant reduction in blood glucose in the male group (35%; p < 0.01), transaminases activity in both sexes (AST and ALT; ~35%; p < 0.05), and urea (20%; p < 0.01) in the female group was observed with the lasiodiplodan treatment. The results showed that sub-chronic treatments with lasiodiplodan did not generate hematological and histopathological alterations leading to signs of toxicity in healthy mice, independent of gender. PMID:23208465

  1. Toxicological Assessment of β-(1à6-Glucan (Lasiodiplodan in Mice during a 28-Day Feeding Study by Gavage

    Directory of Open Access Journals (Sweden)

    Janaína A. Túrmina

    2012-12-01

    Full Text Available Studies evaluating the toxicity caused by fungal exopolysaccharides of the β-(1®6-D-glucan type are rare. In this study, the toxicological effects of sub-chronic treatments with lasiodiplodan (β-(1®6-D-glucan from Lasiodiplodia theobromae MMPI were evaluated in mice through the assessment of biochemical, hematological, and histopathological alterations. Thirty-two mice (16 male, 16 female were used in this study divided in two groups; one group received lasiodiplodan (50 mg/kg body weight daily for 28 days via gavage, and another (control group received saline during the same period. Blood samples were collected via cardiac puncture for hematological and biochemical analyses. Liver, heart, kidney, and spleen were collected for histopathological analysis. Statistical analysis was performed through one-way analysis of variance and only p < 0.05 F-values were presented. Significant reduction in blood glucose in the male group (35%; p < 0.01, transaminases activity in both sexes (AST and ALT; ~35%; p < 0.05, and urea (20%; p < 0.01 in the female group was observed with the lasiodiplodan treatment. The results showed that sub-chronic treatments with lasiodiplodan did not generate hematological and histopathological alterations leading to signs of toxicity in healthy mice, independent of gender.

  2. Admission cell free DNA levels predict 28-day mortality in patients with severe sepsis in intensive care.

    Directory of Open Access Journals (Sweden)

    Avital Avriel

    Full Text Available The aim of the current study is to assess the mortality prediction accuracy of circulating cell-free DNA (CFD level at admission measured by a new simplified method.CFD levels were measured by a direct fluorescence assay in severe sepsis patients on intensive care unit (ICU admission. In-hospital and/or twenty eight day all-cause mortality was the primary outcome.Out of 108 patients with median APACHE II of 20, 32.4% have died in hospital/or at 28-day. CFD levels were higher in decedents: median 3469.0 vs. 1659 ng/ml, p<0.001. In multivariable model APACHE II score and CFD (quartiles were significantly associated with the mortality: odds ratio of 1.05, p = 0.049 and 2.57, p<0.001 per quartile respectively. C-statistics for the models was 0.79 for CFD and 0.68 for APACHE II. Integrated discrimination improvement (IDI analyses showed that CFD and CFD+APACHE II score models had better discriminatory ability than APACHE II score alone.CFD level assessed by a new, simple fluorometric-assay is an accurate predictor of acute mortality among ICU patients with severe sepsis. Comparison of CFD to APACHE II score and Procalcitonin (PCT, suggests that CFD has the potential to improve clinical decision making.

  3. In vivo study with quartz-containing ceramic dusts: Inflammatory effects of two factory samples in lungs after intratracheal instillation in a 28-day study with rats

    Energy Technology Data Exchange (ETDEWEB)

    Creutzenberg, O; Ziemann, C; Hansen, T; Ernst, H [Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover (Germany); Jackson, P; Cartlidge, D [CERAM Research Ltd., Stoke-on-Trent (United Kingdom); Brown, R, E-mail: otto.creutzenberg@item.fraunhofer.d [TOXSERVICES, Stretton (United Kingdom)

    2009-02-01

    As various quartz polymorphs react differently in lungs, a differentiation of effects is needed while setting occupational exposure levels. The objective of this European Collective Research Project SILICERAM was to characterize differences in biological activity of four quartz species, i.) 2 quartz-containing materials collected at typical ceramic manufacturing sites (Tableware granulate, TG and Tableware cast, TC) versus ii.) a designed ceramic dust sample (Contrived Sample, CS) and iii.) ground quartz DQ12 (well-characterised standard quartz (Positive Control, PC) and TiO{sub 2} (negative control). TG and TC had been selected as the most promising two candidates based on a preceding in vitro screening of 5 factory samples. Total doses of 5 mg per rat of the TG and TC, 1.1 mg of the CS and 0.33 mg of the PC corresponding to 0.29, 0.16, 0.29 and 0.29 mg quartz per rat, respectively, were administered to rats by intratracheal instillation. After 3 days, bronchoalveolar lavagate (BAL) analysis resulted in polymorphonuclear neutrophil (PMN) levels of 15%, 25%, 0.6% and 25% in the TG, TC, CS and PC groups, respectively. At 28 days, the values were 29%, 20%, 7% and 45%. Histopathologically, the TG and TC groups showed very slight to slight effects, the PC group, however, stronger effects after the same period. In conclusion, the following ranking was found: PC > TG > TC > CS > TiO{sub 2} > Vehicle Control. Thus, a clear differentiation of effects for TG and TC, CS and PC was found. From a regulatory point of view, the substance-specific toxic potentials of TG and TC may need to be considered when devising occupational exposure limits.

  4. Detection of the effects of repeated dose combined propoxur and heavy metal exposure by measurement of certain toxicological, haematological and immune function parameters in rats.

    Science.gov (United States)

    Institóris, L; Siroki, O; Undeger, U; Basaran, N; Banerjee, B D; Dési, I

    2001-06-21

    In the present study, an immunotoxicity test system, containing general toxicological (body weight gain, organ weights), haematological (WBC,RBC, Ht, mean cell volume of the RBCs, cell content of the femoral bone marrow), and immune function (PFC assay, DTH reaction) investigations, was used for detection the effects of a 4 weeks repeated low dose combined oral exposure of male Wistar rats with propoxur and the heavy metals arsenic or mercury. Two doses of the compounds were used: a higher one (the lowest dose which resulted in significant change of at least one parameter examined in previous dose-effect experiments), and a lower one (the highest dose which proved to be non-effective). The applied doses were: 8.51 and 0.851 mg kg(-1) of propoxur, 13.3 and 3.33 mg kg(-1) of NaAsO(2), and 3.20 and 0.40 mg kg(-1) of HgCl(2). In the combination treatment, the high dose of propoxur was combined with the low dose of arsenic or mercury, and the high doses of each heavy metals were combined with the low dose of propoxur. The main finding of this study was that some of the combinations significantly altered the relative weight of liver, adrenals and kidneys, related to both the untreated and the high dose internal control. Among the immune functions examined, only the PFC content of the spleen showed a trend of changes in certain combinations versus the corresponding high dose control. According to the present results, combined exposure with propoxur and the heavy metals examined can modify the detection limit of the single compounds and/or may alter their toxic effects.

  5. Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race

    Directory of Open Access Journals (Sweden)

    Hatley Holly

    2010-07-01

    Full Text Available Abstract Purpose The effects of creatine supplementation on muscle metabolism and exercise performance during a simulated endurance road race was investigated. Methods Twelve adult male (27.3 ± 1.0 yr, 178.6 ± 1.4 cm, 78.0 ± 2.5 kg, 8.9 ± 1.1 %fat endurance-trained (53.3 ± 2.0 ml* kg-1* min-1, cycling ~160 km/wk cyclists completed a simulated road race on a cycle ergometer (Lode, consisting of a two-hour cycling bout at 60% of peak aerobic capacity (VO2peak with three 10-second sprints performed at 110% VO2 peak every 15 minutes. Cyclists completed the 2-hr cycling bout before and after dietary creatine monohydrate or placebo supplementation (3 g/day for 28 days. Muscle biopsies were taken at rest and five minutes before the end of the two-hour ride. Results There was a 24.5 ± 10.0% increase in resting muscle total creatine and 38.4 ± 23.9% increase in muscle creatine phosphate in the creatine group (P 2 peak, were not affected by creatine supplementation. Submaximal oxygen consumption near the end of the two-hour ride was decreased by approximately 10% by creatine supplementation (P +14.0 ± 6.3% than the placebo group (-10.4 ± 4.4%; P Conclusions It can be concluded that although creatine supplementation may increase resting muscle total creatine, muscle creatine phosphate, and plasma volume, and may lead to a reduction in oxygen consumption during submaximal exercise, creatine supplementation does not improve sprint performance at the end of endurance cycling exercise.

  6. Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hyunmin Kang

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV extracted from bee venom and administered in Sprague-Dawley (SD rats. Methods:Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg. We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E staining to identify any abnormalities caused by the SBV treatment. Results:During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC, and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion:Our findings suggest that the No Observed Adverse Effect Level (NOAEL of SBV is approximately 0.07 mg/kg in male and female SD rats.

  7. Characterization of allergic response induced by repeated dermal exposure of IL-4/Luc/CNS-1 transgenic mice to low dose formaldehyde

    OpenAIRE

    Kwak, Moon-Hwa; Kim, Ji-Eun; Go, Jun; Koh, Eun-Kyoung; Song, Sung-Hwa; Sung, Ji-Eun; Yang, Seung-Yun; An, Beum-Soo; Jung, Young-Jin; Lee, Jae-Ho; Lim, Yong; Hwang, Dae-Youn

    2014-01-01

    Although formaldehyde (FA) is known to be a major allergen responsible for allergic contact dermatitis, there are conflicting reports regarding correlation between FA exposure and interleukin (IL-4) expression. To investigate whether allergic responses including IL-4 expression were induced by repeated dermal exposure to low dose FA, alterations in the luciferase signal and allergic phenotypes were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice containing luciferase cDNA under control of the...

  8. Use of a statistical model to predict the potential for repeated dose and developmental toxicity of dermally administered crude oil and relation to reproductive toxicity.

    Science.gov (United States)

    McKee, Richard H; Nicolich, Mark; Roy, Timothy; White, Russell; Daughtrey, Wayne C

    2014-01-01

    Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general.

  9. Repeated irradiations with γ-rays at a dose of 0.5 Gy may exacerbate asthma

    International Nuclear Information System (INIS)

    We previously showed that 0.5 Gy whole-body γ-ray irradiation with a single or small number of repeated exposures inhibits tumor growth in mice, via elevation of the IFNγ/IL-4 ratio concomitantly with a decrease in the percentage of B cells. Here we examined whether repeated 0.5 Gy γ-rays irradiation can improve asthma in an ovalbumin (OVA)-induced asthmatic mouse model. We found that repeated irradiation (10 times) with 0.5 Gy of γ-rays significantly increased total IgE in comparison with the disease-control group. The levels of IL-4 and IL-5 were also significantly higher in the γ-ray-irradiated group, while that of IFN-γ was significantly lower, resulting in a further decrease of the IFN-γ/IL-4 ratio from the normal value. These results indicate that the repeated irradiation with γ-rays may exacerbate asthma, and may have opposite effects on different immune reactions unlike the irradiation with a single or small number of repeated exposures. (author)

  10. Analgesia induced by repeated exposure to low dose X-rays in mice, and involvement of the accessory olfactory system in modulation of the radiation effects

    International Nuclear Information System (INIS)

    The effects of low-dose X-rays on mouse nociceptive behavior were examined using a formalin injected test which rated the amount of time the animals spent licking the injected hind-paw. Male ICR White Swiss mice showed a marked suppression of licking behavior after repeated low-dose X-irradiation (5 cGy/day, 6 consecutive days). The most profound effect was observed on the day 30 after irradiation. The decline of licking behavior, however, was not observed at all following olfactory bulbectomy or vomeronasal tract cut. The analgesic effects could be observed in writhing animals administered acetic-acid intraperitoneally. Moreover, analgesia was totally blocked by the administration of N-nitro-L-arginine, a nitric oxide synthase inhibitor, to accessory olfactory bulbs prior to the exposure. The present results indicate that the olfactory system plays an important role in modulation of radiation-induced analgesia, and a possible involvement of nitric oxide in the formation of recognition memory subjected to repeated X-rays. Relatively higher doses (5 cGy x 9 days, 5 cGy x 12 days), however, did not induce such effects, namely, the decline of nociceptive response was limited to the animals irradiated with the smaller dose. (author)

  11. Study on a 4-Week Recovery Test of Sweet Bee Venom after a 13-Week, Repeated, Intramuscular Dose Toxicity Test in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Chungsan Lim

    2014-06-01

    Full Text Available Objectives:This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV in Sprague-Dawley (SD rats. Methods:Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results:(1 Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2 The rats in the high-dose group showed no significant changes in weight compared to the control group. (3 No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs, and biochemistry were observed among the recovery groups. (4 No changes in organ weights were observed during the recovery period. (5 Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion:The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

  12. PHARMACODYNAMIC EQUIVALENCE OF USING 3-MONTH AND 28-DAY SUSTAINED-RELEASE DECAPEPTYL DEPOT FORMULATIONS IN PATIENTS WITH ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    P. Teillac

    2009-01-01

    Full Text Available Objective: to evaluate the pharmacodynamic equivalence of 3-month and 28-day formulations of tryptoreline, a sustained-release luteininghormone (LH-releasing hormone analogue.Subjects and methods. The patients who had a verified diagnosis of locally advanced or metastatic prostate cancer were randomized intogroups to have either one injection of a 3-month dosage form (n = 63 or 3 injections of a 28-day formulation at 28-day intervals (n = 68.The onset rate of drug-induced castration, which was defined as a percentage of the patients achieving a plasma testosterone level of ≤0.5ng/ml, was compared on day 84 (i.e. thrice every 28 days. The plasma profiles of testosterone, LH, and tryptoreline, as well as the changesin the plasma concentration of prostate-specific antigen (PCA from the baseline values were estimated within 3 months (from the initiationof therapy to day 91.Results. In the 3-month and 28-day groups, the onset rate of drug-induced castration was 98 and 96%, respectively (at confidenceintervals (94.2% bilaterally in [-8.1%; 9.6%]. The median time for drug-induced castration was 18.8 and 18.5 days, respective-ly (p = 0.86; log-rank test. The ratios of the mean peak plasma concentrations to AUC91 of the two formulations for testosteroneand LH were within 0.80; 1.25 equivalence interval. By day 91, the mean PSA level was decreased by 91.0 and 91.7%, respec-tively (p = 0.73.Conclusion. The use of the two formulations during 3 months is pharmacologically equal.  

  13. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after......To evaluate dose proportionality and absolute bioavailability of a new enteric-coated pellet formulation of pamidronate disodium (AREDIA), nine females (aged 52-66 years) were given three different single peroral doses of pamidronate disodium (75, 150, and 300 mg) and an i.v. infusion of 15 mg over...

  14. Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge

    OpenAIRE

    Schulze Johannes; Voss Sandra; Zissler Ulrich; Rose Markus A; Zielen Stefan; Schubert Ralf

    2012-01-01

    Abstract Background Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation. Methods A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma ...

  15. Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs.

    Science.gov (United States)

    Bergadano, Alessandra; Andersen, Ole K; Arendt-Nielsen, Lars; Theurillat, Regula; Thormann, Wolfgang; Spadavecchia, Claudia

    2009-11-01

    This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg(-1) bolus and at a dose rate of 10 microg kg(-1) min(-1)) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography. Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog. PMID:18706837

  16. Anti-tumor effect of repeated low dose of pEgr-IFN γ-Endostatin gene-radiotherapy on mice bearing lewis lung carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the anti-tumor effect of repeated low dose pEgr-IFN γ-Endostatin gene-radiotherapy on mice bearing Lewis lung carcinoma. Methods: Mice bearing Lewis lung carcinoma were divided randomly into control, 10 Gy, 4 x 2.5 Gy, 4 x P, P + 10 Gy and 4 x (P + 2.5 Gy) group. The pEgr-IFN γ-Endostatin plasmid packaged with liposome was injected into tumors which were irradiated by X-ray 36 h later. Tumor growth rates at different time were observed after gene-radiotherapy. Number of lung metastatic nodes and tumor weight of the mice were detected 18 d after gene-radiotherapy. Results: Tumor growth rate of the mice in gene-radiotherapy for four-time group was significantly lower than that for only once group 12-18 d after gene-radiotherapy. Number of lung metastatic nodes and tumor weight of the mice in gene-radiotherapy for four-time group were significantly lower than those for only once group 18 d after gene-radiotherapy. Conclusion: Anti-tumor effect of repeated low dose pEgr- IFN γ-Endostatin gene-radiotherapy is better than that of high dose for only once. (authors)

  17. Evaluation of a New Method for Calculation of Cumulative Doses in the Rectum Wall using Repeat CT Scans

    International Nuclear Information System (INIS)

    The rectum wall is an important organ at risk during irradiation of the prostate, the bladder and other organs in the pelvis. It is therefore of great interest to be able reliably to predict normal tissue complication probabilities (NTCPs) for this organ. Because the rectum wall is a hollow organ capable of large deformations between fractions, dose estimates from a single CT are unreliable, and thereby also NTCP estimates. In this study two methods for calculations of cumulative dose distributions from repetitive CT scans are compared. The first is a method presented in this article that uses tracking of volume elements for a direct summation of the doses delivered in the treatment fractions. The other, presented earlier, is based on information from dose-volume histograms. The comparisons were made in terms of equivalent uniform doses (EUDs) and NTCPs. The methods were also compared with mean values of EUD and NTCP values from individual CT scans. The study showed that with the relatively symmetric beam arrangements normally used for treatment of prostate and bladder cancer, it is not necessary to use the more laborious method of element tracking. However, an introduction of artificial lateral rectum movements revealed that element tracking is necessary in less symmetric situations

  18. Efficacy and safety of fixed-dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children.

    Directory of Open Access Journals (Sweden)

    Adoke Yeka

    Full Text Available The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT, artesunate-amodiaquine (ASAQ and artemether-lumefantrine (AL are well established for single episodes of uncomplicated Plasmodium falciparum malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1-26. For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5% was non-inferior to that for AL (97.0%; 95% CI [-0.028; 0.037]. PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2-18, ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in <0.5% of cases per episode, abnormal liver function tests occurred in 0.3% to 1.4% of cases. Both regimens were safe and effective for repeated treatment of malaria.Current Controlled Trials NCT00699920.

  19. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS). PMID:25786522

  20. Repeated exposure of male mice to low doses of lipopolysaccharide: dose and time dependent development of behavioral sensitization and tolerance in an automated light-dark anxiety test.

    Science.gov (United States)

    Banasikowski, Tomek J; Cloutier, Caylen J; Ossenkopp, Klaus-Peter; Kavaliers, Martin

    2015-06-01

    Although lipopolysaccharide (LPS) is widely used to examine immune behavior relationships there has been little consideration of the effects of low doses and the roles of sensitization and, or tolerance. Here low doses of LPS (1.0, 5.0 and 25.0 μg/kg) were peripherally administered to male mice on Days 1, 4, 28 and 32 after a baseline recording of anxiety-like behaviors in an automated light-dark apparatus (total time in the light chamber, number of light-dark transitions, nose pokes into the light chamber). LPS at 1.0 μg/kg, while having no significant effects on anxiety-like behaviors in the light-dark test on Days 1 and 4, displayed sensitization with the mice exhibiting significantly enhanced anxiety-like responses on Days 28 and 32. LPS at 5.0 μg/kg had no consistent significant effects on anxiety-like behavior on Days 1 and 4, with sensitization and enhanced anxiety-like behaviors on Day 28 followed by tolerance on Day 32. LPS at 25 μg/kg significantly enhanced anxiety-like behaviors on Day 1, followed by tolerance on Day 4, which was not evident by Day 28 and re-emerged on Day 32. There was a similar overall pattern of sensitization and tolerance for LPS-induced decreases in locomotor activity in the safe dark chamber, without, however, any significant effects on activity in the riskier light chamber. This shows that low doses of LPS induce anxiety-like behavior and these effects are subject to sensitization and tolerance in a dose, context, and time related manner.

  1. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Kerkhof, E M; Put, R W van der; Raaymakers, B W; Heide, U A van der; Vulpen, M van; Lagendijk, J J W [Department of Radiotherapy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht (Netherlands)], E-mail: E.Kerkhof@umcutrecht.nl

    2008-10-21

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  2. Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning

    Science.gov (United States)

    Kerkhof, E. M.; van der Put, R. W.; Raaymakers, B. W.; van der Heide, U. A.; van Vulpen, M.; Lagendijk, J. J. W.

    2008-10-01

    In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

  3. Assessment of absorbed dose and therapeutic response of tumor in repeated high-dose I-131 anti-CD20 monoclonal antibody (rituximab) radioimmunotherapy for non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Lim, Sang Moo; Kim, Kyeong Min [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    We assessed the therapeutic dose absorbed to the tumor and response in repeated RIT with I-131 rituximab for NHL. Patients with NHL (n=6) were administered a therapeutic dose of I-131 rituximab (192.527.0 mCi). The number of repeated administration was 3 for all patients. Total 12 measurable tumor regions were assessed at the time of each RIT. Whole-body (WB) planar images with anterior and posterior views were acquired sequentially at 5 min, 5hr, 24hr, 48hr, and 72hr post-injection using gamma camera. F-18-FDG PET/CT was performed before (within 7 days) and after (on Day 30) RIT. From PET/CT image acquired before RIT, maximum intensity projection (MIP) image of coronal view was acquired. Serial WB planar images were overlaid to the coronal MIP PET image, respectively, by means of registration using 4 fiducial marks (bilateral shoulder and buttock) implemented in AMIDE software. On registered MIP PET and WB planar images, both 2D-ROIs were drawn on the region of tumor and background nearby tumor. The shape of 2D-ROI of tumor was determined from the MIP PET image. The volume of tumor was measured from the CT image, the % change of tumor volume before and after RIT was used in evaluation of the therapeutic response. The values of CT-based tumor volume were 8.216.3cc. The values of absorbed dose for tumor and the % changes of tumor volume before and after RIT were 231.8603.0rad, and 55.548.7%, respectively, and did not show the linear relationship (r=0.2787). The values of absorbed dose for tumor and the % changes of tumor volume did not correlate with the number of repeated administration (p>0.05, ANOVA). Aligning PET and planar images could estimate the quantitative values of absorbed dose to tumor. The data suggest that repeated RIT with I-131 rituximab is necessary for NHL, because single-RIT is insufficient to achieve remission of disease.

  4. Image-Based Assessment and Clinical Significance of Absorbed Radiation Dose to Tumor in Repeated High-Dose {sup 131}I Anti-CD20 Monoclonal Antibody (Rituximab) Radioimmunotherapy for Non-Hodgkin's Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Kim, Kyeong Min; Woo, Sang Keun; Choi, Tae Hyun; Kang, Hye Jin; Oh, Dong Hyun; Kim, Byeong Il; Choen, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-02-15

    We assessed the absorbed dose to the tumor (Dose tumor) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with {sup 131}I rituximab for NHL. Patients with NHL (n=4) were administered a therapeutic dose of {sup 131}I rituximab. Serial WB planar images after RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROIs were drawn on the region of tumor (n=7) and left medial thigh as background, and Dosetumor was calculated. The correlation between Dosetumor and the CT-based tumor volume change after RIT was analyzed. The differences of Dosetumor and the tumor volume change according to the number of RIT were also assessed. The values of absorbed dose were 397.7{+-}646.2cGy (53.0{approx}2853.0cGy). The values of CT-based tumor volume were 11.3{+-}9.1 cc (2.9{approx}34.2cc), and the % changes of tumor volume before and after RIT were -29.8{+-}44.3% (-100.0%{approx}+42.5%), respectively. Dosetumor and the tumor volume change did not show the linear relationship (p>0.05). Dosetumor and the tumor volume change did not correlate with the number of repeated administration (p>0.05). We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

  5. Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To define the maximum-tolerated dose (MTD) and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods: Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m2 D1 and 5-fluorouracil 500 mg/m2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m2 and 5- fluorouracil 100 mg/m2. Every. cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m2, 5-fluorouracil 700 mg/m2. MTD was defined as cisplatin 52.5 mg/m2, 5- fiuorouracil 700 mg/m2. The major side effect were radiation-induced esophagitis, leucopenia, nausea, vomiting and anorexia. Conclusion: Maximun tolerated dose of cisplatin with 5-fiuorouracil in concurrent ehemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m2 D1,5-fluorouracil 700 mg/m2 D1-5, repeated 4 times every 28 days. (authors)

  6. Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach.

    Science.gov (United States)

    Benourad, Fouzia; Kahvecioglu, Zehra; Youcef-Benkada, Mokhtar; Colet, Jean-Marie

    2014-10-01

    In the field of natural extracts, research generally focuses on the study of their biological activities for food, cosmetic, or pharmacological purposes. The evaluation of their adverse effects is often overlooked. In this study, the extracts of Thymus vulgaris L. were obtained by two different extraction methods. Intraperitoneal injections of both extracts were given daily for four days to male Wistar Han rats, at two different doses for each extract. The evaluation of the potential toxic effects included histopathological examination of liver, kidney, and lung tissues, as well as serum biochemistry of liver and kidney parameters, and (1)H-NMR-based metabonomic profiles of urine. The results showed that no histopathological changes were observed in the liver and kidney in rats treated with both extracts of thyme. Serum biochemical investigations revealed significant increases in blood urea nitrogen, creatinine, and uric acid in animals treated with polyphenolic extract at both doses. In these latter groups, metabonomic analysis revealed alterations in a number of urine metabolites involved in the energy metabolism in liver mitochondria. Indeed, the results showed alterations of glycolysis, Krebs cycle, and β-oxidative pathways as evidenced by increases in lactate and ketone bodies, and decreases in citrate, α-ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine. In conclusion, this work showed that i.p. injection of repeated doses of thyme extracts causes some disturbances of intermediary metabolism in rats. The metabonomic study revealed interesting data which could be further used to determine the cellular pathways affected by such treatments.

  7. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme;

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment....... Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (microCT) demonstrated that these effects were not due to changes in cancer progression. The difference...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...

  8. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    Science.gov (United States)

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. PMID:25857839

  9. Development of immunity against viral and bacterial antigens after repeated exposures to suberythemal doses of ultraviolet light

    Directory of Open Access Journals (Sweden)

    S. A. Snopov

    2012-01-01

    Full Text Available The effects of ultraviolet (UV radiation on human infectious immunity are not well studied. On the one hand, solar and artificial UU sources have been shown to change cytokine levels in human skin, lymphocyte subpopulation counts in parepheral blood, lymphocyte DNA synthesis and prolifarative response to mitogens. On the other hand, there are just only one or two observations suggesting an influence of UV radiation on human infection course. For instance, UV irradiations have been reported to induce a reccurence of orofacial vesicular lesions caused by herpes siplex virus. Moreover, there is a lack of data concerning immune effects of suberythtemal doses of UV in spite of a long history of using them by Russian prophylactic medicine. In this work we questioned whether such suberythemal UV exposures can affect the immune responses of children to infectious conjunctivitis, to simultaneous measles and polio vaccinations and to simultaneous polio and diphtheria-tetanus vaccinations. In peripheral blood of vaccinated children we examined leukocyte counts (monocytes, neutrophils, eosinophils, lymphocytes, percentages of lymphocyte subpopulations (CD3+, CD20+, CD4+, CD8+, CD25+, HLADR+, concentrations of cytokines (IL-1 beta, TNF-alpha, IFN- amma и IL-10, DNA-synthetic activity of lymphocytes and titres of antibodies against measles and diphtheria toxin. We observed no local or systemic reactions to the vaccines in the UV-group while a moderate rise in body temperature occured in several children from unexposed group. In the blood of childeren from UV-group we found increases in CD25+ и HLADR+ cell percentages, IL- 1 beta and IL-10 concentrations, PWMinduced DNA synthesis in mononuclears, and no decreases in formation of antibodies against measles and diphreria. We concluded that suberythemal UV exposures of children modulated their further responses to imminisations perhaps through the activation of a T helper 2-like

  10. Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days.

    Science.gov (United States)

    Guo, Tai L; Germolec, Dori R; Collins, Bradley J; Luebke, Robert W; Auttachoat, Wimolnut; Smith, Matthew J; White, Kimber L

    2011-01-01

    Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B(6)C(3)F(1) mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days. No statistically significant differences in drinking water consumption, body weight, body weight gain, organ weights, or hematological parameters between the exposed and control animals were noted during the experimental period. There were no changes in the percentages and numbers of total B-lymphocytes, T-lymphocytes, CD4(+) and CD8(+) T-lymphocytes, natural killer (NK) cells, and macrophages in the spleen. Exposure to chloramine did not affect the IgM antibody-forming cell response to sheep red blood cells (SRBC) or anti-SRBC IgM antibody production. Minimal effects, judged to be biologically insignificant, were observed in the mixed-leukocyte response and NK activity. In conclusion, chloramine produced no toxicological and immunotoxic effects in female B(6)C(3)F(1) mice when administered for 28 days in the drinking water at concentrations ranging from 2-200 ppm.

  11. Characterization of pulmonary protein profiles in response to zinc oxide nanoparticles in mice: a 24-hour and 28-day follow-up study

    Directory of Open Access Journals (Sweden)

    Pan CH

    2015-07-01

    Full Text Available Chih-Hong Pan,1,2,* Kai-Jen Chuang,3,4,* Jen-Kun Chen,5 Ta-Chih Hsiao,6 Ching-Huang Lai,2 Tim P Jones,7 Kelly A BéruBé,8 Gui-Bing Hong,9 Kin-Fai Ho,10,11 Hsiao-Chi Chuang12,13 1Institute of Occupational Safety and Health, Council of Labor Affairs, Executive Yuan, 2School of Public Health, National Defense Medical Center, 3School of Public Health, College of Public Health and Nutrition, 4Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 5Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, 6Graduate Institute of Environmental Engineering, National Central University, Taoyuan, Taiwan; 7School of Earth and Ocean Sciences, 8School of Biosciences, Cardiff University, Cardiff, Wales, UK; 9Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan; 10Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 11Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 12School of Respiratory Therapy, College of Medicine, 13Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Although zinc oxide nanoparticles (ZnONPs are recognized to cause systemic disorders, little is known about the mechanisms that underlie the time-dependent differences that occur after exposure. The objective of this study was to investigate the mechanistic differences at 24 hours and 28 days after the exposure of BALB/c mice to ZnONPs via intratracheal instillation. An isobaric tag for the relative and absolute quantitation coupled with liquid chromatography/tandem mass spectrometry was used to identify the differential

  12. Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate ovalbumin-induced allergic asthma in mice.

    Science.gov (United States)

    Park, Bum Soo; Hong, Gwan Ui; Ro, Jai Youl

    2013-05-01

    Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice. PMID:23560633

  13. Selected oxidative stress parameters after single and repeated administration of octabromodiphenyl ether to rats

    Directory of Open Access Journals (Sweden)

    Elżbieta Bruchajzer

    2014-10-01

    Full Text Available Objectives: Octabromodiphenyl ether (OctaBDE was used as a flame retardant applied mostly in the manufacture of plastics utilized in the electrical and electronic industries. Owing to its long half-life and being regarded as an environmental pollutant, OctaBDE, like other polybrominated diphenyl ethers, has been classified as a persistent organic pollutant (POP. This study was carried out to assess the effects of oxidative stress (redox homeostasis induced in rats by OctaBDE. Material and Methods: Female Wistar rats exposed intragastrically to OctaBDE at single (25, 200 or 2000 mg/kg b.w., or repeated (0.4, 2, 8, 40 or 200 mg/kg/day doses during 7–28 days were used in the experiment. Selected oxidative stress parameters were determined in the liver and blood serum. Results: Administration (single or repeated of OctaBDE to rats resulted in the impaired redox homeostasis, as evidenced by the increased levels of reduced (GSH and oxidized (GSSG glutathione in the liver, the reduced total antioxidant status (TAS in serum and the increased concentration of malondialdehyde (MDA in the liver. After multiple doses of OctaBDE, elevated activity of glutathione transferase (GST in the liver was also noted. Conclusions: After repeated administration of OctaBDE at the lowest dose (0.4 mg/kg/day, changes were observed in the parameters (MDA, TAS, GSSG indicative of oxidative stress.

  14. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes

    Science.gov (United States)

    Garcia-Manero, G; Gore, S D; Kambhampati, S; Scott, B; Tefferi, A; Cogle, C R; Edenfield, W J; Hetzer, J; Kumar, K; Laille, E; Shi, T; MacBeth, K J; Skikne, B

    2016-01-01

    CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and DNA methyltransferase inhibitor in clinical development for treatment of hematologic malignancies. CC-486 administered for 7 days per 28-day treatment cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half-life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may increase the number of AZA-affected diseased target cells and maximize therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS) received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of repeated 28-day cycles. Median patient age was 72 years (range 31–87) and 75% of patients had International Prognostic Scoring System Intermediate-1 risk MDS. Median number of CC-486 treatment cycles was 7 (range 2–24) for the 14-day dosing schedule and 6 (1–24) for the 21-day schedule. Overall response (complete or partial remission, red blood cell (RBC) or platelet transfusion independence (TI), or hematologic improvement) (International Working Group 2006) was attained by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC TI rates were similar with both dosing schedules (31% and 38%, respectively). CC-486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may provide effective long-term treatment for patients with lower-risk MDS. PMID:26442612

  15. Phase I Trial of Escalating-dose Cisplatin with 5-fluorouracil and Concurrent Radiotherapy in Chinese Patients with Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Zhao,Yan-Nan

    2008-02-01

    Full Text Available We defined the maximum-tolerated dose (MTD of chemoradiotherapy (cisplatin (CDDP with 5-fluorouracil (5-FU and concurrent chemoradiotherapy for Chinese patients with esophageal cancer. Twenty-one previously untreated patients with primary esophageal cancer were entered into this study. Escalating doses of CDDP with 5-FU were administered in a modified Fibonacci sequence, with concurrent conventional fractionation radiotherapy (CFR of 60 Gy or 50 Gy. The starting doses were CDDP 37.5 mg/m2 on day 1, and 5-FU 500 mg/m2 on days 1-5, respectively. The regimen was repeated 4 times every 28 days. If no dose-limiting toxicity (DLT was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be 1 dose level below the level at which DLT appeared. DLT was grade 3 radiation-induced esophagitis at a dose level of CDDP 60 mg/m2 with 5-FU 700 mg/m2 and concurrent 60 Gy CFR. MTD was defined as CDDP 52.5 mg/m2 with 5-FU 700 mg/m2 and concurrent 50 Gy CFR. The MTD of CDDP with 5-FU and in concurrent chemoradiotherapy for Chinese patients with esophageal cancer is CDDP 52.5 mg/m2 on day 1 and 5FU 700 mg/m2 on days 1-5, repeated 4 times every 28 days, and concurrent 50 Gy CFR. Further evaluation of this regimen in a prospective phase II trial is ongoing.

  16. Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

    Directory of Open Access Journals (Sweden)

    Barry Aichatou

    2011-08-01

    Full Text Available Abstract Background The use of artemisinin-based combination therapy (ACT is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ and artemether-lumefantrine (AL - in subsequent episodes of Plasmodium falciparum malaria. Methods A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR after polymerase chain reaction (PCR correction on day 28 for the first episode. Results A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182 and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182, PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03. No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during

  17. Risk of sensitization in healthy adults following repeated administration of rdESAT-6 skin test reagent by the Mantoux injection technique

    DEFF Research Database (Denmark)

    Lillebaek, Troels; Bergstedt, Winnie; Tingskov, Pernille N;

    2009-01-01

    Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase...... 31 (3%) volunteers showed a positive skin reaction (sensitization) upon a second injection of rdESAT-6 after 28days and an increased IFN-gamma response to ESAT-6. For 7 (23%) of the volunteers, local adverse reactions related to the product were registered, but all reactions were mild and predictable....... In conclusion, repeated injections of the rdESAT-6 skin test reagent are safe, and sensitization occurs at a low rate, especially if the time span between succeeding doses is wide....

  18. Repeated Miscarriage

    Science.gov (United States)

    f AQ FREQUENTLY ASKED QUESTIONS FAQ100 PREGNANCY Repeated Miscarriages • What is recurrent pregnancy loss? • What is the likelihood of having repeated miscarriages? • What is the most common cause of miscarriage? • ...

  19. Should Patient Setup in Lung Cancer Be Based on the Primary Tumor? An Analysis of Tumor Coverage and Normal Tissue Dose Using Repeated Positron Emission Tomography/Computed Tomography Imaging

    International Nuclear Information System (INIS)

    Purpose: Evaluation of the dose distribution for lung cancer patients using a patient setup procedure based on the bony anatomy or the primary tumor. Methods and materials: For 39 patients with non–small-cell lung cancer, the planning fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan was registered to a repeated FDG-PET/CT scan made in the second week of treatment. Two patient setup methods were analyzed based on the bony anatomy or the primary tumor. The original treatment plan was copied to the repeated scan, and target and normal tissue structures were delineated. Dose distributions were analyzed using dose–volume histograms for the primary tumor, lymph nodes, lungs, and spinal cord. Results: One patient showed decreased dose coverage of the primary tumor caused by progressive disease and required replanning to achieve adequate coverage. For the other patients, the minimum dose to the primary tumor did not significantly deviate from the planned dose: −0.2 ± 1.7% (p = 0.71) and −0.1 ± 1.7% (p = 0.85) for the bony anatomy setup and the primary tumor setup, respectively. For patients (n = 31) with nodal involvement, 10% showed a decrease in minimum dose larger than 5% for the bony anatomy setup and 13% for the primary tumor setup. The mean lung dose exceeded the maximum allowed 20 Gy in 21% of the patients for the bony anatomy setup and in 13% for the primary tumor setup, whereas for the spinal cord this occurred in 10% and 13% of the patients, respectively. Conclusions: In 10% and 13% of patients with nodal involvement, setup based on bony anatomy or primary tumor, respectively, led to important dose deviations in nodal target volumes. Overdosage of critical structures occurred in 10–20% of the patients. In cases of progressive disease, repeated imaging revealed underdosage of the primary tumor. Development of practical ways for setup procedures based on repeated high-quality imaging of all tumor sites during

  20. Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males

    OpenAIRE

    Leutholtz Brian; Redd Liz; Hudson Geoffrey; Buford Thomas; Cooke Matt; Shelmadine Brian; Willoughby Darryn S

    2009-01-01

    Abstract Purpose This study determined the effects of 28 days of heavy resistance exercise combined with the nutritional supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers. Methods Eighteen non-resistance-trained males participated in a resistance training program (3 × 10-RM) 4 times/wk for 28 days while also ingesting 27 g/day of placebo (PL) or NO-Shotgun® (NO) 30 min prior to exercise. Data were analyzed...

  1. Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

    Science.gov (United States)

    Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

    2014-05-01

    In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

  2. The Safety and Effectiveness of Single and Repeat Dosing of Intra-Articular Anti-Tumour Necrosis Factor Treatment after Failure of Intra-Articular Steroids

    OpenAIRE

    Chia, Justin; POPE, JANET

    2011-01-01

    Objectives: To determine if intra-articular (ia) anti-tumour necrosis factor (TNF) yielded benefit in patients failing ia steroid injections and determine the safety and durability of single and repeated ia anti-TNF treatment in inflammatory arthritis. Methods: Patients with inflammatory arthritis having one or two active joints, and having failed previous ia steroids were injected with ia adalimumab or ia etanercept mixed with triamcinolone and lidocaine via a retrospective chart audit. Resu...

  3. Exploring mechanisms of fatigue during repeated exercise and the dose dependent effects of carbohydrate and protein ingestion: study protocol for a randomised controlled trial

    OpenAIRE

    Alghannam, Abdullah F; Tsintzas, Kostas; Thompson, Dylan; Bilzon, James; Betts, James A.

    2014-01-01

    Background Muscle glycogen has been well established as the primary metabolic energy substrate during physical exercise of moderate- to high-intensity and has accordingly been implicated as a limiting factor when such activity is sustained for a prolonged duration. However, the role of this substrate during repeated exercise after limited recovery is less clear, with ongoing debate regarding how recovery processes can best be supported via nutritional intervention. The aim of this project is ...

  4. Repeat-dose toxicology evaluation in cynomolgus monkeys of AVI-4658, a phosphorodiamidate morpholino oligomer (PMO) drug for the treatment of duchenne muscular dystrophy.

    Science.gov (United States)

    Sazani, Peter; Ness, Kirk P Van; Weller, Doreen L; Poage, Duane W; Palyada, Kiran; Shrewsbury, Stephen B

    2011-05-01

    AVI-4658 is a phosphorodiamidate morpholino oligomer (PMO) drug designed to restore dystrophin expression in a subset of patients with Duchenne muscular dystrophy (DMD). Previous reports demonstrated this clinical proof-of-principle in patients with DMD following intramuscular injection of AVI-4658. This preclinical study evaluated the toxicity and toxicokinetic profile of AVI-4658 when administered either intravenously (IV) or subcutaneously (SC) to cynomolgus monkeys once weekly over 12 weeks, at doses up to the maximum feasible dose of 320 mg/kg per injection. No drug-related effects were noted on survival, clinical observations, body weight, food consumption, opthalmoscopic or electrocardiographic evaluations, hematology, clinical chemistry, urinalysis, organ weights, and macroscopic evaluations. Drug-related microscopic renal effects were dose-dependent, apparently reversible, and included basophilic granules (minimal), basophilic tubules (minimal to moderate), and tubular vacuolation (minimal to mild). These data establish the tolerability of AVI-4658 at doses up to and including the maximum feasible dose of 320 mg/kg by IV bolus or SC injection.

  5. Action of 50 R X-ray doses on the breeding function of C3H strain mice - effect of splitting the dose, action of repeated irradiations on successive generations

    International Nuclear Information System (INIS)

    X-rays exposure effect was studied on C3H strain mice, at the standpoint of the effects produced on breeding function. The method used with this purpose was the following: single doses 20 - 30 - 40 and 50 R/dose, fractional doses: 50 R/total dose, divided in 2 - 5 - 10 or 25 irradiations distributed in one month duration. The offsprings were irradiated at the same doses than the parents, consanguinity being maintained. Statistical treatment of results was carried out, that led at the following conclusions: 1) Couples receiving single exposure of 50 R or two exposures of 25 R at one month interval give comparable results. Fractional doses do not involve the slightest diminution of X-rays effect. 2) 30 R exposure brings about a decrease in fertility, with an increase in abortions. Fertility of 20 R irradiated couples remains below controls. 3) After ten times 5 R and twenty-five 2 R, the number of abortions is the largest. Ovarian function is particularly sensitive to X-rays; one may think that twenty-five 2 R give injuries conditioning non-viability of conception products, smaller doses should produce mutations and yield births of altered genotype individuals. (author)

  6. Predictors of non-invasive therapy and 28-day-case fatality in elderly compared to younger patients with acute myocardial infarction: an observational study from the MONICA/KORA Myocardial Infarction Registry

    OpenAIRE

    Amann, Ute; Kirchberger, Inge; Heier, Margit; Thilo, Christian; Kuch, Bernhard; Peters, Annette; Meisinger, Christa

    2016-01-01

    Background A substantial proportion of patients with acute myocardial infarction (AMI) did not receive invasive therapy, defined as percutaneous coronary intervention and/or coronary artery bypass grafting. Aims of this study were to evaluate predictors of non-invasive therapy in elderly compared to younger AMI patients and to assess the association between invasive therapy and 28-day-case fatality. Methods From the German population-based registry, 3475 persons, consecutively hospitalized wi...

  7. Safety evaluation of AB-LIFE(®) (Lactobacillus plantarum CECT 7527, 7528 and 7529): Antibiotic resistance and 90-day repeated-dose study in rats.

    Science.gov (United States)

    Mukerji, Pushkor; Roper, Jason M; Stahl, Buffy; Smith, Amy B; Burns, Frank; Rae, Jessica Caverly; Yeung, Nicolas; Lyra, Anna; Svärd, Laura; Saarinen, Markku T; Alhoniemi, Esa; Ibarra, Alvin; Ouwehand, Arthur C

    2016-06-01

    AB-LIFE(®) is a probiotic product consisting of equal parts of three strains of Lactobacillus plantarum (CECT 7527, 7528, and 7529) blended with inert excipients. Whole genome sequencing was performed on each of the three strains. Antibiotic resistance was evaluated by genomic mining for resistance genes, and assessment for transferability. No risk of transfer potential was identified for any antibiotic resistance genes in the three strains. AB-LIFE(®) was evaluated for potential subchronic oral toxicity in rats, with dosages of 300 and 1000 mg/kg BW/day (equivalent to 5.55 × 10(10) and 1.85 × 10(11) CFU/kg BW/day). Survival of the three test strains through the gastrointestinal tract was supported by fecal analysis. No adverse effects were identified with respect to in-life parameters, clinical or anatomic pathology, translocation, or fecal chemical analyses. The no-observed-adverse-effect level (NOAEL) for AB-LIFE(®) in male and female rats was 1000 mg/kg BW/day (1.85 × 10(11) CFU of AB-LIFE(®)/kg BW/day), the highest dose level evaluated. These results, in conjunction with a previous acute toxicity study in rats, support the conclusion that AB-LIFE(®) is safe for human consumption. PMID:27016492

  8. Ketoprofen versus paracetamol (acetaminophen) or ibuprofen in the management of fever: results of two randomized, double-blind, double-dummy, parallel-group, repeated-dose, multicentre, phase III studies in children.

    Science.gov (United States)

    Kokki, Hannu; Kokki, Merja

    2010-01-01

    Fever is a common symptom in children and one of the major concerns of parents of younger and preschool-age children. To compare the efficacy and safety of ketoprofen with that of paracetamol (acetaminophen) and ibuprofen in the treatment of febrile conditions in children. Two prospective, randomized, double-blind, double-dummy, repeated-dose, multicentre, phase III studies with two parallel groups in each study were conducted in primary-care outpatient clinics. Children aged 6 months to 6 years presenting with a febrile condition and an oral body temperature of > or =38.8 degrees C or rectal temperature of > or =39 degrees C were eligible for inclusion. Patients were randomized to receive either ketoprofen syrup 0.5 mg/kg, ibuprofen suspension 5 mg/kg or paracetamol suspension 15 mg/kg every 6 hours by the oral route. The primary outcome measure was the change in temperature at 3 hours (H3), compared with baseline (H0). All three treatments provided similar mean maximum decreases of 1.4-1.5 degrees C in body temperature at H3 compared with H0. Use of ketoprofen was not associated with any increased risk of adverse events compared with the two reference compounds. Ketoprofen 0.5 mg/kg appeared to be equivalent to the standard antipyretic doses of the reference products ibuprofen 5 mg/kg and paracetamol 15 mg/kg. Ketoprofen at the 0.5 mg/kg dose should be an effective and safe option for symptomatic management of fever in children. PMID:20380479

  9. Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males

    Directory of Open Access Journals (Sweden)

    Leutholtz Brian

    2009-08-01

    Full Text Available Abstract Purpose This study determined the effects of 28 days of heavy resistance exercise combined with the nutritional supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers. Methods Eighteen non-resistance-trained males participated in a resistance training program (3 × 10-RM 4 times/wk for 28 days while also ingesting 27 g/day of placebo (PL or NO-Shotgun® (NO 30 min prior to exercise. Data were analyzed with separate 2 × 2 ANOVA and t-tests (p Results Total body mass was increased in both groups (p = 0.001, but without any significant increases in total body water (p = 0.77. No significant changes occurred with fat mass (p = 0.62; however fat-free mass did increase with training (p = 0.001, and NO was significantly greater than PL (p = 0.001. Bench press strength for NO was significantly greater than PL (p = 0.003. Myofibrillar protein increased with training (p = 0.001, with NO being significantly greater than PL (p = 0.019. Serum IGF-1 (p = 0.046 and HGF (p = 0.06 were significantly increased with training and for NO HGF was greater than PL (p = 0.002. Muscle phosphorylated c-met was increased with training for both groups (p = 0.019. Total DNA was increased in both groups (p = 0.006, while NO was significantly greater than PL (p = 0.038. For DNA/protein, PL was decreased and NO was not changed (p = 0.014. All of the myogenic regulatory factors were increased with training; however, NO was shown to be significantly greater than PL for Myo-D (p = 0.008 and MRF-4 (p = 0.022. No significant differences were located for any of the whole blood and serum clinical chemistry markers (p > 0.05. Conclusion When combined with heavy resistance training for 28 days, NO-Shotgun® is not associated with any negative side effects, nor does it abnormally impact any of the clinical chemistry markers. Rather, NO-Shotgun® effectively increases muscle strength and mass

  10. Comparison in the calculation of committed effective dose using the ICRP 30 and ICRP 60 models for a repeated incorporation by inhalation of I-125; Comparacion en el calculo de la dosis efectiva comprometida usando los modelos del ICRP 30 y del ICRP 60 para una incorporacion repetida por inhalacion de I-125

    Energy Technology Data Exchange (ETDEWEB)

    Carreno P, A.L.; Cortes C, A. [CNSNS, Dr. Barragan 779, Col. Narvarte, Mexico D.F. (Mexico); Alonso V, G.; Serrano P, F. [IPN, Edificio de Fisica Avanzada Zacatenco, 07300 Mexico D.F. (Mexico)

    2005-07-01

    Presently work, a comparison in the calculation of committed effective dose using the models of the ICRP 30 and those of the ICRP 60 for the analysis of internal dose due to repeated incorporation of I-125 is shown. The estimations of incorporated activity are obtained starting from the proportionate data for an exercise of inter comparison, with which it should be determined the internal dose later on. For to estimate the initial activity incorporated by repeated dose was assumed that this it was given through of multiple individual incorporations which happened in the middle points of the monitoring periods. The results using the models of the ICRP 30 and of the ICRP 60 are compared and the causes of the differences are analyzed. (Author)

  11. Effect of Beta alanine and sodium bicarbonate supplementation on repeated-sprint performance.

    Science.gov (United States)

    Ducker, Kagan J; Dawson, Brian; Wallman, Karen E

    2013-12-01

    This study aimed to investigate if combining beta alanine (BA) and sodium bicarbonate (NaHCO3) supplementation could lead to enhanced repeated-sprint performance in team-sport athletes, beyond what is possible with either supplement alone. Participants (n = 24) completed duplicate trials of a repeated-sprint test (3 sets; 6 × 20 m departing every 25 seconds, 4 minutes active recovery between sets) and were then allocated into 4 groups as follows: BA only (n = 6; 28 days BA, acute sodium chloride placebo); NaHCO3 only (n = 6; 28 days glucose placebo, acute NaHCO3); BA/NaHCO3 (n = 6; 28 days BA, acute NaHCO3); placebo only (n = 6; 28 days glucose placebo, acute sodium chloride placebo), then completed duplicate trials postsupplementation. Sodium bicarbonate alone resulted in moderate effect size (d = 0.40-0.71) and "likely" and "very likely" benefit for overall total sprint times (TST) and for each individual set and for first sprint (sets 2 and 3) and best sprint time (sets 2 and 3). Combining BA and NaHCO3 resulted in "possible" to "likely" benefits for overall TST and for sets 2 and 3. First sprint (set 3) and best sprint time (sets 2 and 3) also showed "likely" benefit after this trial. The BA and placebo groups showed no differences in performance after supplementation. In conclusion, these results indicate that supplementation with acute NaHCO3 improved repeated-sprint performance more than either a combination of NaHCO3 and BA or BA alone.

  12. The Efficacy of Magnesium Sulfate Loading on Microalbuminuria Following SIRS:One Step forward in Dosing

    Directory of Open Access Journals (Sweden)

    Atabak Najafi

    2012-10-01

    Full Text Available Backgrounds:Magnesium has been known for its antioxidative and antiinflammatory properties in many studies. In this study two dosing regimens of magnesium were compared with a placebocontrol group in order to investigate safety and efficacy of high doses of intravenous magnesium sulfate infusion on critically ill trauma patients. Inflammatory and oxidative factors were measured in this trial.Methods:45 trauma patients with systemic inflammatory response syndromes (SIRS were randomly assigned into 2 treatment and one placebo groups. The high dose group received 15 g MgSO4, low dose group received 7.5 g of MgSO4 over 4 hour infusion, and placebo groupreceived saline alone. The initial and post magnesium sulfate injections levels of tumor necrosis factor alpha (TNF-α, total antioxidant power and lipid peroxidation were measured after 6, 18 and 36 hours. The pre-infusion along with 6 and 36 hour level ofmicroalbuminuria were also determined.Results:Repeated measurements illustrated that there was no significant difference in TNF-α, total antioxidant power and lipid peroxidation levels among groups during the period of analysis.The microalbuminuria at 36 hour post infusion of high dose group was lower than that of control group (p = 0.024. Patient’s mortality (28 day was similar among all treatment groups. Both magnesium infusion groups tolerated the drug without experiencing anycomplications.Conclusion:No evidence for antioxidative and antiinflammatory effects of magnesium in traumatic SIRS positive patients was found. Magnesium in high doses may be recommended for traumaticpatients with SIRS status to prevent microalbuminuria.

  13. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  14. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    International Nuclear Information System (INIS)

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80–90). The mean retreatment dose was 84.4 Gy (range, 60–90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  15. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  16. Effects of 28 days of resistance exercise while consuming commercially available pre- and post-workout supplements, NO-Shotgun® and NO-Synthesize® on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers in males

    OpenAIRE

    Spillane Mike; Schwarz Neil; Leddy Sarah; Correa Tracie; Minter Melodie; Longoria Victoria; Willoughby Darryn S

    2011-01-01

    Abstract Purpose The effects of 28 days of heavy resistance training while ingesting the pre- and post-workout supplements, NO-Shotgun® and NO-Synthesize® were determined on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers. Methods Nineteen non-resistance-trained males participated in a resistance training program 4 times/week for 28 days while either ingesting 27 g/day of carbohydrate (CARB) or NO-Shotgun® 30 min pre-exercise and 27 g/day ...

  17. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  18. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  19. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  20. Single and Multiple Dose Pharmacokinetics, Pharmacodynamics and Safety of the Novel Lipoprotein-Associated Phospholipase A2 Enzyme Inhibitor Darapladib in Healthy Chinese Subjects: An Open Label Phase-1 Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Chaoying Hu

    Full Text Available Darapladib is a lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibitor. This study evaluated the pharmacokinetics, pharmacodynamics and safety of darapladib in healthy Chinese subjects.Twenty-four subjects received darapladib 160 mg orally, approximately 1 hour after a standard breakfast, as a single dose and once daily for 28 days. Non-compartmental methods were used to determine the single and multiple dose pharmacokinetics of darapladib and its metabolite SB-553253. Repeat dose Lp-PLA2 activity and safety were evaluated.Systemic exposure (AUC(0-T, Cmax geometric mean (CVb% of darapladib was higher after multiple-dosing (519 ng.h/mL (33.3%, 34.4 ng/mL (49.9% compared to single-dose administration (153 ng.h/mL (69.0%, 17.9 ng/mL (55.2%. The steady-state accumulation ratio was less than unity (Rs = 0.80, indicating time-dependent pharmacokinetics of darapladib. Darapladib steady-state was reached by Day 14 of once daily dosing. Systemic exposure to SB-553253 was lower than darapladib with median (SB-553253: darapladib ratios for AUC(0-τ of 0.0786 for single dose and 0.0532 for multiple dose administration. On Day 28, pre-dose and maximum inhibition of Lp-PLA2 activity was approximately 70% and 75% relative to the baseline value, respectively and was dependent of darapladib concentration. The most common adverse events (≥ 21% subjects were abnormal faeces, abnormal urine odour, diarrhoea and nasopharyngitis.Darapladib 160 mg single and repeat doses were profiled in healthy Chinese subjects. Single dose systemic exposure to darapladib in healthy Chinese subjects was consistent with that observed previously in Western subjects whereas steady-state systemic exposure was approximately 65% higher in Chinese than Western subjects. The Lp-PLA2 activity and adverse event profile were similar in healthy Chinese and previous reports in Western subjects. Ethnic-specific dose adjustment of darapladib is not considered necessary for the Chinese

  1. Clinical experience and results of treatment with suprofen in pediatrics. 3rd communication: Antipyretic effect and tolerability of repeat doses of suprofen and paracetamol syrup in hospitalized children/A single-blind study.

    Science.gov (United States)

    Weippl, G; Michos, N; Sundal, E J; Stocker, H

    1985-01-01

    Antipyretic effect and tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol), syrup and paracetamol (acetaminophen) were compared within the scope of the present randomized single-blind study; the test population included a total of 115 children ranging in age from 6 months to 12 years. All patients were admitted to the hospital with an average temperature of 39.3 degrees C, their disease being caused by bacterial or viral infections. The dose levels for treatment with syrup depended upon the children's age and body weight. Treatment was in most cases given for two days; a three-times-a-day schedule was used. The (rectal) temperature as well as pulse and respiratory rates were measured prior to treatment and 0.5, 1, 1.5, 2, 3, 4, 5, 6 h after first administration of the test preparations. The results showed that the antipyretic effect of suprofen was in both age groups at all rating times statistically significantly superior to that of paracetamol. Pulse and respiratory rates dropped in both age groups after treatment; the means were within the normal range at all rating times. Adverse drug reactions were seen in 5 patients on suprofen and in 3 cases on paracetamol. It is, however, questionable whether such reactions are drug-dependent. PMID:3911963

  2. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  3. Honesty through repeated interactions.

    Science.gov (United States)

    Rich, Patricia; Zollman, Kevin J S

    2016-04-21

    In the study of signaling, it is well known that the cost of deception is an essential element for stable honest signaling in nature. In this paper, we show how costs for deception can arise endogenously from repeated interactions between individuals. Utilizing the Sir Philip Sidney game as an illustrative case, we show that repeated interactions can sustain honesty with no observable signal costs, even when deception cannot be directly observed. We provide a number of potential experimental tests for this theory which distinguish it from the available alternatives. PMID:26869213

  4. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  5. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  6. Flexibility of oral cholera vaccine dosing-a randomized controlled trial measuring immune responses following alternative vaccination schedules in a cholera hyper-endemic zone.

    Directory of Open Access Journals (Sweden)

    Suman Kanungo

    2015-03-01

    Full Text Available BACKGROUND: A bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response. METHODOLOGY/PRINCIPAL FINDINGS: In this double blind randomized controlled non-inferiority trial, 356 Indian, non-pregnant residents aged 1 year or older were randomized to receive two doses of oral cholera vaccine at 14 and 28 day intervals. We compared vibriocidal immune responses between these schedules. Among adults, no significant differences were noted when comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose regimens administered at a 14 day interval (55% vs the 28 day interval (58%. Similarly, no differences in seroconversion were demonstrated in children comparing the 14 (80% and 28 day intervals (77%. Following 14 and 28 day dosing intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for V. cholerae O139, but similar between dosing schedules for adults (20%, 20% and children (28%, 20%. CONCLUSIONS/SIGNIFICANCE: Comparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.

  7. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  8. OECD 28-days oral toxicity study on fumonisin B1

    NARCIS (Netherlands)

    Nijs M de; Egmond HP van; Jong WH de; Loveren H van; LPI; ARO; MGB

    1999-01-01

    Het beschreven experiment werd uitgevoerd om inzicht te verkrijgen over effecten van lage doseringen fumonisine B1 op target organen en het immuunsysteem. Mannelijke ratten van drie weken oud werden oraal via maagsonde behandeld met 0, 0,19, 0,75 of 3 mg/kg lichaamsgewicht fumonisine B1, dagelij

  9. PERINATAL TUBERCULOSIS WITH MILLIARY PATTERN IN INFANT AGED 28 DAYS

    Directory of Open Access Journals (Sweden)

    Dian Savitri

    2015-07-01

    Full Text Available Perinatal  tuberculosis  (TB was a very  rare  case.  Its  clinical manifestations  could mimic bacterialinfection. The clinical course was often fulminant and characterized by dissemination and meningitis.Its mortality was very high, could achieve 100% in untreated patient. We reported a case of infant aged28  days  admitted with  breathlessness,  fever,  and  poor  feeding.  Physical  examination  showedbreathlessness, pale, lethargy, and hepatomegaly. Chest radiograph showed a feature of milliary patternwith fine tubercles in both lung, supported with positive result on gastric aspirates for acid fast bacilli3 days respectively. Gastric aspirate culture for Mycobacterium tuberculosis showed positive result.Patient then diagnosed with perinatal TB with milliary pattern. This condition was accompanied withsevere sepsis and meningitis. Four TB regimens (isoniazid, rifampisin, pirazinamide, and ethambutol,corticosteroid, antibiotics were given. The patient was eventually died after receiving TB therapy for 13days. [MEDICINA 2014;45:208-212].

  10. Effects of 28 days of resistance exercise while consuming commercially available pre- and post-workout supplements, NO-Shotgun® and NO-Synthesize® on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers in males

    Directory of Open Access Journals (Sweden)

    Spillane Mike

    2011-11-01

    Full Text Available Abstract Purpose The effects of 28 days of heavy resistance training while ingesting the pre- and post-workout supplements, NO-Shotgun® and NO-Synthesize® were determined on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers. Methods Nineteen non-resistance-trained males participated in a resistance training program 4 times/week for 28 days while either ingesting 27 g/day of carbohydrate (CARB or NO-Shotgun® 30 min pre-exercise and 27 g/day of carbohydrate or NO- Synthesize® 30 min post-exercise (NOSS. Data were analyzed with separate 2 × 2 ANOVA (p Results Total body mass was increased in both groups (p = 0.001, but not different between groups. Fat mass was unchanged with CARB, but NOSS decreased fat mass (p = 0.026. Both groups increased fat-free mass (p = 0.001; however, the increases were greater with NOSS (p = 0.023. NOSS underwent greater increases in upper-body (p = 0.023 and lower-body (p = 0.035 strength than CARB. Myofibrillar protein significantly increased in both groups (p = 0.041, with NOSS being greater than CARB (p = 0.049. All of the MHC isoforms were significantly increased in both groups; however, NOSS was greater than CARB for MHC 1 (p = 0.013 and MHC 2A (p = 0.046. All of the myogenic regulatory factors were significantly increased in both groups; however, NOSS was greater than CARB for Myo-D (p = 0.038 and MRF-4 (p = 0.001. For the whole blood and serum clinical chemistry markers, all variables remained within normal clinical ranges. Conclusions Heavy resistance training for 28 days, with NO-Shotgun® and NO-Synthesize® ingested before and after exercise, respectively, significantly improved body composition and increased muscle mass and performance without abnormally impacting any of the clinical chemistry markers.

  11. Heart failure re-admission: measuring the ever shortening gap between repeat heart failure hospitalizations.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Bakal

    Full Text Available Many quality-of-care and risk prediction metrics rely on time to first rehospitalization even though heart failure (HF patients may undergo several repeat hospitalizations. The aim of this study is to compare repeat hospitalization models. Using a population-based cohort of 40,667 patients, we examined both HF and all cause re-hospitalizations using up to five years of follow-up. Two models were examined: the gap-time model which estimates the adjusted time between hospitalizations and a multistate model which considered patients to be in one of four states; community-dwelling, in hospital for HF, in hospital for any reason, or dead. The transition probabilities and times were then modeled using patient characteristics and number of repeat hospitalizations. We found that during the five years of follow-up roughly half of the patients returned for a subsequent hospitalization for each repeat hospitalization. Additionally, we noted that the unadjusted time between hospitalizations was reduced ∼40% between each successive hospitalization. After adjustment each additional hospitalization was associated with a 28 day (95% CI: 22-35 reduction in time spent out of hospital. A similar pattern was seen when considering the four state model. A large proportion of patients had multiple repeat hospitalizations. Extending the gap between hospitalizations should be an important goal of treatment evaluation.

  12. Pharmacokinetics of rectal paracetamol after repeated dosing in children

    DEFF Research Database (Denmark)

    Hahn, T W; Henneberg, S W; Holm-Knudsen, R J;

    2000-01-01

    Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P

  13. Pharmacokinetics of rectal paracetamol after repeated dosing in children

    DEFF Research Database (Denmark)

    Hahn, T W; Henneberg, S W; Holm-Knudsen, R J;

    2000-01-01

    Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P <0.05) between saliva and serum concentrations. A one-...

  14. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-01

    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

  15. Repeat Customer Success in Extension

    Science.gov (United States)

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  16. Evaluation of radiation dose to neonates in a special care baby unit

    Science.gov (United States)

    Alzimami, K.; Sulieman, A.; Yousif, A.; Babikir, E.; Salih, I.

    2014-11-01

    The purpose of this study was to evaluate the patient entrance surface dose (ESD), organ dose and effective dose for neonates in the special care baby unit (SCBU) up to 28 days after birth. A total of 135 patients were examined during 4 months. ESDs were calculated from patient exposure parameters using DosCal software. Effective doses were calculated using software from the National Radiological Protection Board (NRPB). The mean patient ESD per procedure was 80±0.02 μGy. The mean and range of the effective dose per procedure were 0.02 (0.01-0.3) mSv. The radiation dose in this study was higher compared to previous studies. A dedicated X-ray machine with additional filtration is recommended for patient dose reductions.

  17. Phase I trial of low-dose oral Clofarabine in myelodysplastic syndromes patients who have failed frontline therapy.

    Science.gov (United States)

    Rudrapatna, Venkatesh K; Morley, Kimberly; Boucher, Kenneth M; Pierson, Andrew S; Shull, Christian T; Kushner, James P; Shami, Paul J

    2015-08-01

    We investigated protracted low-dose oral Clofarabine for the treatment of myelodysplastic syndromes (MDS). Adults with an International Prognostic Scoring System (IPSS) score of INT-1 or higher who had failed first line therapy were eligible. INT-1 patients had to be transfusion-dependent. We started with oral Clofarabine at 5mg (fixed dose) daily for 10 consecutive days on a 28-day cycle. Toxicity prompted a modification to 1mg PO daily for 10 days and then 1mg PO daily for 7 days. Patients received treatment indefinitely until loss of response or unacceptable toxicity. Nine patients (5 women) were enrolled and evaluable (median age 65 years; range 55-81). A 10-day regimen of oral Clofarabine at 5mg/day induced Grade IV pancytopenia. A dose of 1 mg/day for 7/28 days was very well tolerated without significant toxicity. Three patients had responses (2 with responses lasting up to 21 and 51 cycles) defined as stable disease in spite of no significant change on bone marrow evaluation. Low-dose oral Clofarabine (1mg daily for 7/28 days) proved both effective and safe for patients with MDS who had failed prior therapy. This patient population is particularly sensitive to more protracted Clofarabine treatment schedules. PMID:26038120

  18. Evaluating dose response from flexible dose clinical trials

    Directory of Open Access Journals (Sweden)

    Baron David

    2008-01-01

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

  19. Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

    International Nuclear Information System (INIS)

    We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2). Female C57BL/6 mice were exposed to rutile nano-TiO2 via single intratracheal instillations of 18, 54, and 162 μg/mouse. Mice were sampled 1, 3, and 28 days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO2 in the lungs up to 28 days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (± 1.3 fold; p 2 in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities. - Highlights: • Pulmonary effects following exposure to low doses of nano-TiO2 were examined. • Particle retention in lungs was assessed using nanoscale hyperspectral microscopy. • Particles persisted up to 28 days in lungs in all dose groups. • Inflammation was the pathway affected in the high dose group at all time points. • Ion homeostasis and muscle activity pathways were affected in the low dose group

  20. Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults.

    Directory of Open Access Journals (Sweden)

    Curtis Cooper

    Full Text Available INTRODUCTION: The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy. METHODS: A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years: two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™ was used. Serum hemagglutinin inhibition (HAI activity for the three influenza strains in the vaccine was measured to assess immunogenicity. RESULTS: 297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL and HIV RNA (76% of patients with viral load <50 copies/mL were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥ 40 =  31-58%. Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related. CONCLUSION: Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00764998.

  1. Dose limits

    International Nuclear Information System (INIS)

    The dose limit is defined to be the level of harmfulness which must not be exceeded, so that an activity can be exercised in a regular manner without running a risk unacceptable to man and the society. The paper examines the effects of radiation categorised into stochastic and non-stochastic. Dose limits for workers and the public are discussed

  2. Saturation of repeated quantum measurements

    Science.gov (United States)

    Haapasalo, Erkka; Heinosaari, Teiko; Kuramochi, Yui

    2016-08-01

    We study sequential measurement scenarios where the system is repeatedly subjected to the same measurement process. We first provide examples of such repeated measurements where further repetitions of the measurement do not increase our knowledge on the system after some finite number of measurement steps. We also prove, however, that repeating the Lüders measurement of an unsharp two-outcome observable never saturates in this sense, and we characterize the observable measured in the limit of infinitely many repetitions. Our result implies that a repeated measurement can be used to correct the inherent noise of an unsharp observable.

  3. Supplemental dose of antithrombin use in disseminated intravascular coagulation patients after abdominal sepsis.

    Science.gov (United States)

    Tagami, Takashi; Matsui, Hiroki; Fushimi, Kiyohide; Yasunaga, Hideo

    2015-08-31

    The effectiveness of supplemental dose antithrombin administration (1,500 to 3,000 IU/ day) for patients with sepsis-associated disseminated intravascular coagulation (DIC), especially sepsis due to abdominal origin, remains uncertain. This was a retrospective cohort study of patients with mechanically ventilated septic shock and DIC after emergency surgery for perforation of the lower intestinal tract using a nationwide administrative database, Japanese Diagnosis Procedure Combination inpatient database. A total of 2,164 patients treated at 612 hospitals during the 33-month study period between 2010 and 2013 were divided into an antithrombin group (n=1,021) and a control group (n=1,143), from which 518 propensity score-matched pairs were generated. Although there was no significant 28-day mortality difference between the two groups in the unmatched groups (control vs antithrombin: 25.7 vs 22.9 %; difference, 2.8 %; 95 % confidence interval [CI], -0.8-6.4), a significant difference existed between the two groups in propensity-score weighted groups (26.3 vs 21.7 %; difference, 4.6 %; 95 % CI, 2.0-7.1) and propensity-score matched groups (27.6 vs 19.9 %; difference, 7.7 %; 95 % CI, 2.5-12.9). Logistic regression analyses showed a significant association between antithrombin use and lower 28-day mortality in propensity-matched groups (odds ratio, 0.65; 95 % CI, 0.49-0.87). Analysis using the hospital antithrombin-prescribing rate as an instrumental variable showed that receipt of antithrombin was associated with a 6.5 % (95 % CI, 0.05-13.0) reduction in 28-day mortality. Supplemental dose of antithrombin administration may be associated with reduced 28-day mortality in sepsis-associated DIC patients after emergency laparotomy for intestinal perforation.

  4. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  5. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  6. Repeated treatments of drooling with botulinum toxin B in neurology

    DEFF Research Database (Denmark)

    Møller, Eigild; Daugaard, Dorthe; Holm, Ole;

    2015-01-01

    OBJECTIVES: To investigate efficacy, saliva flow, and composition in repeated BoNT-B treatments of drooling. MATERIALS AND METHODS: Seventeen neurological patients (median 66 years), referred for treatment of drooling participated in this observational study. Median total doses of 4000 units...

  7. 78 FR 65594 - Vehicular Repeaters

    Science.gov (United States)

    2013-11-01

    ... Proceedings, 63 FR 24121 (May 1, 1998). Electronic Filers: Comments may be filed electronically using the... COMMISSION 47 CFR Part 90 Vehicular Repeaters AGENCY: Federal Communications Commission. ACTION: Proposed... the Commission's rules to allow the licensing and operation of vehicular repeater systems and...

  8. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  9. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  10. Controllable dose

    International Nuclear Information System (INIS)

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  11. Lisina digestível em dietas de baixa proteína para frangos de corte tipo caipira de um aos 28 dias Digestible lysine in diets containing low protein concentrations for broiler type redneck from 1 to 28 days

    Directory of Open Access Journals (Sweden)

    H.G. Oliveira

    2013-04-01

    Full Text Available Avaliou-se a inclusão de diferentes porcentagens de lisina digestível em dietas de baixa proteína para frangos de corte tipo caipira, machos e fêmeas, com idade entre um e 28 dias. Utilizaram-se 792 machos e 792 fêmeas de linhagem comercial, de um dia de idade, distribuídos em delineamento inteiramente ao acaso, em esquema fatorial 2x6 (sexo x porcentagem de lisina digestível: 0,85; 0,90; 0,95; 1,00; 1,05 e 1,10% com seis repetições de 22 aves. Não foi constatada interação (P>0,05 de sexo versus inclusão de lisina. Observou-se superioridade (P0,05 para conversão alimentar. Da composição centesimal da carcaça, apenas o percentual de matéria mineral foi influenciada (PThe inclusion of different percentages of digestible lysine in low-protein diets was evaluated for male and female free-range broiler chickens, from 1 to 28 days. We used 792 female and 792 male naked neck chickens a day in a completely randomized 2x6 factorial scheme (sex x percentages of digestible lysine: 0.85, 0.90, 0.95, 1.00, 1.05 and1.10% with six replicates of 22 broilers. No interaction of sex versus lysine was found. Superiority was observed (P0.05 in food conversion.In the chemical composition of the carcass, only thepercentage of mineral matter was influenced (P<0.05 bydigestible lysine levels.It was concluded that the level of 0.85% for type redneck broiler meets the nutritional requirement of digestible lysine in diets containing lower protein concentrations.

  12. Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

    Directory of Open Access Journals (Sweden)

    Olajumoke Omolara Ojo

    Full Text Available Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR and cytochrome P450 side chain cleavage proteins (CYP11A1 were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of

  13. Glasses for high doses dosimetry; Vidros para dosimetria de altas doses

    Energy Technology Data Exchange (ETDEWEB)

    Quezada, Valeria A.C.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

    1995-12-31

    A routine dosimetric system, of low cost, for gamma high doses measurements was established using commercially available glass samples and a special densitometer. Glasses of different kinds, origins and dimensions were studied in relation to their dosimetric properties: repeatability, batch uniformity, re-utilization, thermal fading and dose range. (author). 3 refs., 5 figs., 1 tab.

  14. Dose and dose rate monitor

    International Nuclear Information System (INIS)

    The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137Cs, 241Am and 109Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10-2 to 103 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

  15. Repeated proton beam therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A

  16. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  17. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    International Nuclear Information System (INIS)

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [3H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results

  18. 简化急性生理学评分Ⅲ与其他评分方法对急诊严重脓毒症患者28 d死亡的预测能力比较%Comparison of simplified acute physiology score Ⅲ and other scoring systems in prediction of 28-day ;prognosis in patients with severe sepsis

    Institute of Scientific and Technical Information of China (English)

    李岩; 李春盛

    2015-01-01

    SAPSⅡ评分预测能力相当,可用于对急诊ICU严重脓毒症患者的预后进行预测,但SAPSⅢ评分有不适合预测急诊ICU脓毒症患者预后的选项,导致SAPSⅢ评分在预测急诊ICU脓毒症患者的预后方面并未优于其他评分。%Objective To investigate the power of the simplified acute physiology score Ⅲ ( SAPSⅢ) for prediction of outcome for patients with severe sepsis admitted to the intensive care unit ( ICU ). Methods A retrospective study was conducted. 677 severe sepsis patients with age ≥ 18 years old and the survival time in emergency ICU≥24 hours admitted to the emergency ICU of Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2008 to December 2011 were enrolled. The acute physiology and chronic health evaluationⅡ ( APACHEⅡ), sequential organ failure assessment ( SOFA ), SAPSⅡ, SAPSⅢ, and mortality in emergency department sepsis ( MEDS ) scores were recorded based on the poorest value within 24 hours of ICU admission. The 28-day result as denoted as survival or death was considered as the end point of the study. The ability to predict mortality by the score systems was assessed by using receiver operating characteristic ( ROC ) curve analysis and binary logistic regression models. Results Among the 677 patients with severe sepsis, 284 cases died within 28 days after admission, and the mortality rate was 41.9%. Compared with survivors, the patients in non-survival group was older with higher APACHEⅡ, SOFA, SAPSⅡ, SAPSⅢ, and MEDS scores and higher ratio of underlying diseases, such as primary hypertension and renal dysfunction, and they had more organ injury, higher ratio of lung infection and bacterial infection ( P 0.05 ). The MEDS score in predicting the prognosis was obviously better than that of APACHEⅡ, SOFA, SAPSⅡ, and SAPSⅢscores ( all P<0.05 ). The MEDS score showed the best sensitivity ( 91.5%), and specificity ( 89.1%). The 28-day mortality in cases

  19. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  20. Sequencing Games with Repeated Players

    NARCIS (Netherlands)

    Estevez Fernandez, M.A.; Borm, P.E.M.; Calleja, P.; Hamers, H.J.M.

    2004-01-01

    Two classes of one machine sequencing situations are considered in which each job corresponds to exactly one player but a player may have more than one job to be processed, so called RP(repeated player) sequencing situations.In max-RP sequencing situations it is assumed that each player's cost funct

  1. A Semiparametric Bayesian Model for Repeatedly Repeated Binary Outcomes

    OpenAIRE

    Quintana, Fernando A.; Müller, Peter; Rosner, Gary L.; Mary V Relling

    2008-01-01

    We discuss the analysis of data from single nucleotide polymorphism (SNP) arrays comparing tumor and normal tissues. The data consist of sequences of indicators for loss of heterozygosity (LOH) and involve three nested levels of repetition: chromosomes for a given patient, regions within chromosomes, and SNPs nested within regions. We propose to analyze these data using a semiparametric model for multi-level repeated binary data. At the top level of the hierarchy we assume a sampling model fo...

  2. Directionality switchable gain stabilized linear repeater

    Science.gov (United States)

    Ota, Takayuki; Ohmachi, Tadashi; Aida, Kazuo

    2004-10-01

    We propose a new approach to realize a bidirectional linear repeater suitable for future optical internet networks and fault location in repeater chain with OTDR. The proposed approach is the linear repeater of simple configuration whose directionality is rearranged dynamically by electrical control signal. The repeater is composed of a magneto-optical switch, a circulator, a dynamically gain stabilized unidirectional EDFA, and control circuits. The repeater directionality is rearranged as fast as 0.1ms by an electrical control pulse. It is experimentally confirmed that OTDR with the directionality switchable repeater is feasible for repeater chain. The detailed design and performance of the repeater are also discussed, including the multi-pass interference (MPI) which may arise in the proposed repeater, the effect of the MPI on SNR degradation of the repeater chain and the feed-forward EDFA gain control circuit.

  3. Efficacy analysis on simplified intensity-modulated radiotherapy with high or conventional dose and concurrent chemotherapy for patients with N1 esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the feasibility of simplified intensity-modulated radiotherapy (sIMRT) and concurrent chemotherapy against neck and upper thoracic esophageal carcinoma with lymph node metastasis. Methods: sIMRT plans were designed for 44 patients of neck and upper thoracic esophageal carcinoma with lymph node metastasis, 20 of which underwent high dose sIMRT (hsIMRT group) and 24 underwent conventional dose sIMRT (csIMRT group). Three target volumes were defined: PGTVnd, target volume of lymph node lesion, irradiated to 68.1 Gy (2.27 Gy × 30 fractions) for the hsIMRT group, and 60 Gy (2.0 Gy ×30 fractions) the csIMRT group; PTV1, the target volume of primary lesion, to be irradiate to 63.9 Gy (2.13 Gy × 30 fractions) for the hsIMRT group and 60 Gy (2.0 Gy × 30 fractions) for the csIMRT group; PTV2, the prophylactically irradiated volume, to be irradiated to 54 Gy (1.8 Gy ×30) for both groups. The sIMRT plan included 5 equiangular coplanar beams. All patients received DDP + 5-FU regimen concurrently with radiotherapy at 1 -5 d and 29- 33 d, respectively. Chemotherapy was repeated for two cycles 28 days after the radiotherapy was finished. Results: The treatment was completed for all patients within 6 weeks. During the treatment only one patient with grade 3 acute bronchitis was observed in the hsIMRT group. The complete response (CR) rate for the lymph node lesion of the hsIMRT group was 75% (15/20), significantly higher than that of the csIMRT group [45.8% (11/24), χ2=3.84, P<0.05]. The 1-, 2-, and 3-year progression-free survival rates of the hsIMRT group were 60%, 40%, and 25%, respectively, all significantly higher than those of the csIMRT group (41.7%, 25%, and 8.3% respectively, χ2=4.11, P<0.05). However, there were not significant differences in the total survival rate, and the CR and PR of the esophageal lesion between these 2 groups. The major toxicity observed was grade Ⅰ -Ⅱ leukoctyopenia. Conclusions: sIMRT generates desirable dose

  4. A Repeating Fast Radio Burst

    CERN Document Server

    Spitler, L G; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-01-01

    Fast Radio Bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measures (i.e. integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of the fast radio bursts has led several authors to hypothesise that they originate in cataclysmic astrophysical events. Here we report the detection of ten additional bursts from the direction of FRB121102, using the 305-m Arecibo telescope. These new bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and wh...

  5. Repeatability of Harris Corner Detector

    Institute of Scientific and Technical Information of China (English)

    HU Lili

    2003-01-01

    Interest point detectors are commonly employed to reduce the amount of data to be processed. The ideal interest point detector would robustly select those features which are most appropriate or salient for the application and data at hand. This paper shows that interest points are geometrically stable under different transformations.This property makes interest points very successful in the context of image matching. To measure this property quantatively, we introduce a evaluation criterion: repeatability rate.

  6. A repeating fast radio burst

    Science.gov (United States)

    Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

    2016-03-01

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  7. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  8. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    β-cells against superoxide generated by glycation reaction evoked by high glucose environment. Continuous irradiation at 0.63 mGy/hr from 28 days of age elongates life span, and recovers splenic inflammatory response in Klotho-mice bearing ageing syndrome. The radiation increases anti-oxidants in liver, implicating the prevention of ageing through the suppression of cellular oxidative damages. Our results suggest that low dose/low dose-rate radiation effectively ameliorates diseases related to reactive oxygen species, and elongates life span of animals, at least in part through the stimulation of protective responses against oxidative stress. These findings are important not only for clinical use of low dose/low dose-rate radiation for human diseases, but also for non-cancerous risk estimation at dose and dose rate range argued in legal restrictions. (author)

  9. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  10. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  11. Efeitos da relação metionina + cistina: lisina sobre os desempenhos produtivo e econômico e a qualidade interna e externa dos ovos antes e após 28 dias de armazenamento Effects of methionine + cystine: lysine ratio on the productive and economic performance and internal and external egg quality, before and 28 days after storage

    Directory of Open Access Journals (Sweden)

    José Jordão Filho

    2006-08-01

    .75% of total Lys; T4 = 0.86 Met+Cys: total Lys ratio or 0.70% of Met+Cys and 0.81% of total Lys. The performance variables and economical analysis were evaluated from 44 to 56 weeks old. At the end of trial, ten eggs per treatment were collected ad stored during 28 days for evaluation of internal/external egg quality before and after storage. With the exception of egg mass, no treatment effect on feed intake, egg production, egg weight and egg:mass ratio and egg:dozen ratio and egg shell specific quality was observed. The Met+Cys:Lys ratio of 0.76 or the estimate of 0.70% of total Met+Cys and 0.92% of total Lys can be recommended for the feeding of semiheavily laying hens. It was concluded that the storage affect internal egg quality.

  12. Crowding by a repeating pattern.

    Science.gov (United States)

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  13. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... MB] Read the MMWR Science Clips Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On ... live birth before age 20. Problem Too many teens, ages 15–19, have repeat births. Nearly 1 ...

  14. Automatization and familiarity in repeated checking

    NARCIS (Netherlands)

    Dek, Eliane C P; van den Hout, Marcel A.; Giele, Catharina L.; Engelhard, Iris M.

    2014-01-01

    Repeated checking paradoxically increases memory uncertainty. This study investigated the underlying mechanism of this effect. We hypothesized that as a result of repeated checking, familiarity with stimuli increases, and automatization of the checking procedure occurs, which should result in decrea

  15. Essays in the theory of repeated games

    OpenAIRE

    Osório-Costa, António Miguel

    2010-01-01

    This thesis comprises three essays in economic theory. The first two are in the theory of repeated games. The third is also a theoretical contribution, which mixes con- cepts both from repeated games and the theory of incentives. The first chapter is a novel contribution to frequent monitoring in repeated games. The second one, studies for the first time, infinitely repeated games where the repetitions of the stage game are random. The last chapter, studies the provision of incentives in a pr...

  16. Lambda Exonuclease Digestion of CGG Trinucleotide Repeats

    OpenAIRE

    Conroy, R. S.; Koretsky, A P; Moreland, J.

    2009-01-01

    Fragile X syndrome and other triplet repeat diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. Using magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and na...

  17. ProtRepeatsDB: a database of amino acid repeats in genomes

    Directory of Open Access Journals (Sweden)

    Chauhan Virander S

    2006-07-01

    Full Text Available Abstract Background Genome wide and cross species comparisons of amino acid repeats is an intriguing problem in biology mainly due to the highly polymorphic nature and diverse functions of amino acid repeats. Innate protein repeats constitute vital functional and structural regions in proteins. Repeats are of great consequence in evolution of proteins, as evident from analysis of repeats in different organisms. In the post genomic era, availability of protein sequences encoded in different genomes provides a unique opportunity to perform large scale comparative studies of amino acid repeats. ProtRepeatsDB http://bioinfo.icgeb.res.in/repeats/ is a relational database of perfect and mismatch repeats, access to which is designed as a resource and collection of tools for detection and cross species comparisons of different types of amino acid repeats. Description ProtRepeatsDB (v1.2 consists of perfect as well as mismatch amino acid repeats in the protein sequences of 141 organisms, the genomes of which are now available. The web interface of ProtRepeatsDB consists of different tools to perform repeat s; based on protein IDs, organism name, repeat sequences, and keywords as in FASTA headers, size, frequency, gene ontology (GO annotation IDs and regular expressions (REGEXP describing repeats. These tools also allow formulation of a variety of simple, complex and logical queries to facilitate mining and large-scale cross-species comparisons of amino acid repeats. In addition to this, the database also contains sequence analysis tools to determine repeats in user input sequences. Conclusion ProtRepeatsDB is a multi-organism database of different types of amino acid repeats present in proteins. It integrates useful tools to perform genome wide queries for rapid screening and identification of amino acid repeats and facilitates comparative and evolutionary studies of the repeats. The database is useful for identification of species or organism specific

  18. 47 CFR 97.205 - Repeater station.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Repeater station. 97.205 Section 97.205... SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  19. 47 CFR 22.1015 - Repeater operation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015... Offshore Radiotelephone Service § 22.1015 Repeater operation. Offshore central stations may be used as repeater stations provided that the licensee is able to maintain control of the station, and in...

  20. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    1999-01-01

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  1. Repeated apomorphine administration alters dopamine D1 and D2 receptor densities in pigeon basal telencephalon

    OpenAIRE

    Acerbo, Martin J.; Výboh, Pavel; Košťál, Ľubor; Kubíková, Ľubica; Delius, Juan

    2005-01-01

    When pigeons are repeatedly administered a dose of apomorphine they show an increasing behavioral response, much as rodents do. In birds this expresses itself in an augmented pecking response. This sensitization is assumed to be largely due to a conditioning process. Here we present evidence that sensitization is accompanied by an alteration of the D1 to D2 dopamine receptor densities. An experimental group of pigeons was repeatedly injected with apomorphine, and a control group with saline. ...

  2. General benchmarks for quantum repeaters

    CERN Document Server

    Pirandola, Stefano

    2015-01-01

    Using a technique based on quantum teleportation, we simplify the most general adaptive protocols for key distribution, entanglement distillation and quantum communication over a wide class of quantum channels in arbitrary dimension. Thanks to this method, we bound the ultimate rates for secret key generation and quantum communication through single-mode Gaussian channels and several discrete-variable channels. In particular, we derive exact formulas for the two-way assisted capacities of the bosonic quantum-limited amplifier and the dephasing channel in arbitrary dimension, as well as the secret key capacity of the qubit erasure channel. Our results establish the limits of quantum communication with arbitrary systems and set the most general and precise benchmarks for testing quantum repeaters in both discrete- and continuous-variable settings.

  3. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  4. Profile of water contents in concrete under dry-absorption repeated condition by neutron radiography

    International Nuclear Information System (INIS)

    The authors have examined the moisture content distribution inside concrete, which is closely associated with the durability evaluation of reinforced concrete, using neutron radiography. In particular, they experimentally examined water content distribution in the concrete under environments of repeated drying and water-absorption, and the effects of cracks and temperature on drying. As a result, it was confirmed that moisture was further diffused into the inside and water was accumulated during drying, while generating the increase or decrease of moisture content on the surface. Under the temperature of 20degC, the existence of cracks under 0.05 mm in width did not significantly affect the drying rate of the part within 1 cm from the cracks. The existence of cracks 0.3 mm in width was confirmed to have slightly fastened the drying rate around the cracks. It was also confirmed that under the temperature of 20degC, the change in drying rate was little, and under 50degC, relative moisture content decreased to 60% or less at the position up to 8 cm in depth after 28 days of drying. It was clarified that moisture content was fluctuated inside concrete, and its temporal change was not homogeneous. (A.O.)

  5. Repeated inhalation exposure of Beagle dogs to aerosols of 239PuO2. XII

    International Nuclear Information System (INIS)

    Beagle dogs were exposed once or semi-annually for 10 yr by inhalation to aerosols of 239PuO2 to study the relative doses and effects of these two types of exposures. All exposures have been completed. Dogs exposed at high levels died predominantly of radiation pneumonitis and pulmonary fibrosis. Dogs exposed at lower levels, either once or repeatedly, are dying of a variety of causes including lung cancer. Dogs have survived up to 11 yr after their first exposure. Preliminary results suggest that single and repeated exposures cause similar health effects for equal accumulated radiation doses. (author)

  6. ProRepeat: an integrated repository for studying amino acid tandem repeats in proteins

    NARCIS (Netherlands)

    Luo, H.; Lin, K.; David, A.; Nijveen, H.; Leunissen, J.A.M.

    2012-01-01

    ProRepeat (http://prorepeat.bioinformatics.nl/) is an integrated curated repository and analysis platform for in-depth research on the biological characteristics of amino acid tandem repeats. ProRepeat collects repeats from all proteins included in the UniProt knowledgebase, together with 85 complet

  7. Repeated Sprints: An Independent Not Dependent Variable.

    Science.gov (United States)

    Taylor, Jonathan M; Macpherson, Tom W; Spears, Iain R; Weston, Matthew

    2016-07-01

    The ability to repeatedly perform sprints has traditionally been viewed as a key performance measure in team sports, and the relationship between repeated-sprint ability (RSA) and performance has been explored extensively. However, when reviewing the repeated-sprint profile of team-sports match play it appears that the occurrence of repeated-sprint bouts is sparse, indicating that RSA is not as important to performance as commonly believed. Repeated sprints are, however, a potent and time-efficient training strategy, effective in developing acceleration, speed, explosive leg power, aerobic power, and high-intensity-running performance--all of which are crucial to team-sport performance. As such, we propose that repeated-sprint exercise in team sports should be viewed as an independent variable (eg, a means of developing fitness) as opposed to a dependent variable (eg, a means of assessing fitness/performance). PMID:27197118

  8. Strengthening concept learning by repeated testing.

    Science.gov (United States)

    Wiklund-Hörnqvist, Carola; Jonsson, Bert; Nyberg, Lars

    2014-02-01

    The aim of this study was to examine whether repeated testing with feedback benefits learning compared to rereading of introductory psychology key-concepts in an educational context. The testing effect was examined immediately after practice, after 18 days, and at a five-week delay in a sample of undergraduate students (n = 83). The results revealed that repeated testing with feedback significantly enhanced learning compared to rereading at all delays, demonstrating that repeated retrieval enhances retention compared to repeated encoding in the short- and the long-term. In addition, the effect of repeated testing was beneficial for students irrespectively of working memory capacity. It is argued that teaching methods involving repeated retrieval are important to consider by the educational system.

  9. Competition impedes the recovery of Daphnia magna from repeated insecticide pulses.

    Science.gov (United States)

    Dolciotti, Ida; Foit, Kaarina; Herkelrath, Anna; Liess, Matthias

    2014-02-01

    The effects of multiple insecticide pulses on non-target organisms have rarely been investigated in combination with relevant biotic interactions, such as competition. In this study, we examined the effects of two repeated pulses of the insecticide pirimicarb (3, 10, 24 μg/L) on populations of Daphnia magna with or without competition. To investigate the influence of competition, half of the test systems were supplemented with the pirimicarb-insensitive species Culex pipiens. The pesticide pulses were followed by a recovery period of 28 days, which corresponded to approximately three generation times for D. magna. The one-species setup with the Daphnia populations and the two-species setup with both the Daphnia and Culex populations had a precontamination period of 30 days so that intra- and interspecific competitions were present prior to the insecticide pulse. Short-term effects on the survival of the Daphnia population were observed in both setups immediately after each insecticide pulse at the highest concentration level. In the one-species setup, the short-term effects on population survival were increased by intraspecific competition. However, the Daphnia populations in the one-species setup recovered and reached the control level within approximately two weeks after each insecticide pulse. In contrast, in the two-species setup at the highest concentration, we observed culmination of insecticide effects: the Daphnia populations did not recover and their abundance was below the control level until the end of the observation time. Their recovery was impeded by the presence of the competing species C. pipiens for at least four weeks. At low concentrations, no culmination of effects was observed. We conclude that repeated toxicant pulses on populations that are challenged with interspecific competition may result in a multigenerational culmination of toxicant effects. PMID:24373889

  10. Short Tandem Repeat DNA Internet Database

    Science.gov (United States)

    SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

  11. Benchmark Dose Modeling

    Science.gov (United States)

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  12. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies.

    Directory of Open Access Journals (Sweden)

    Eric Laille

    Full Text Available CC-486 (oral azacitidine is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK and pharmacodynamic (PD profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS, chronic myelomonocytic leukemia (CMML or acute myeloid leukemia (AML from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05 reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle, with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle.ClinicalTrials.gov NCT00528983.

  13. Nephrotoxicity in mice after repeated imaging using 111In- labeled peptides

    NARCIS (Netherlands)

    M.L. Melis (Marleen); E. Vegt (Erik); M.W. Konijnenberg (Mark); M. de Visser (Monique); M. Bijster (Magda); M. Vermeij (Marcel); E.P. Krenning (Eric); O.C. Boerman (Otto); M. de Jong (Marion)

    2010-01-01

    textabstractWe determined the renal radiation dose of a series of111Inlabeled peptides using animal SPECT. Because the animals' health deteriorated, renal toxicity was assessed. Methods: Wild-type and megalin-deficient mice were imaged repeatedly at 3- to 6-wk intervals to quantify renal retention a

  14. Nephrotoxicity in mice after repeated imaging using 111In-labeled peptides.

    NARCIS (Netherlands)

    Melis, M.; Vegt, E.; Konijnenberg, M.W.; Visser, M. de; Bijster, M.; Vermeij, M.; Krenning, E.P.; Boerman, O.C.; Jong, M. de

    2010-01-01

    We determined the renal radiation dose of a series of (111)In-labeled peptides using animal SPECT. Because the animals' health deteriorated, renal toxicity was assessed. METHODS: Wild-type and megalin-deficient mice were imaged repeatedly at 3- to 6-wk intervals to quantify renal retention after inj

  15. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan

    2010-12-15

    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  16. Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Husain, Mainul, E-mail: mainul.husain@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Saber, Anne T., E-mail: ats@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Guo, Charles, E-mail: charles.guo@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Jacobsen, Nicklas R., E-mail: nrj@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Jensen, Keld A., E-mail: kaj@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Yauk, Carole L., E-mail: carole.yauk@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Williams, Andrew, E-mail: andrew.williams@hc-sc.gc.ca [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Vogel, Ulla, E-mail: ubv@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Department of Micro- and Nanotechnology, Technical University of Denmark, Kgs. Lyngby DK-2800 (Denmark); Wallin, Hakan, E-mail: hwa@nrcwe.dk [The Danish NanoSafety Centre, National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Institute of Public Health, University of Copenhagen, Copenhagen DK-1014 (Denmark); Halappanavar, Sabina, E-mail: sabina.halappanavar@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario K1A 0K9 (Canada)

    2013-06-15

    We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO{sub 2}). Female C57BL/6 mice were exposed to rutile nano-TiO{sub 2} via single intratracheal instillations of 18, 54, and 162 μg/mouse. Mice were sampled 1, 3, and 28 days post-exposure. The deposition of nano-TiO{sub 2} in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tissue protein ELISA. Hyperspectral mapping showed dose-dependent retention of nano-TiO{sub 2} in the lungs up to 28 days post-instillation. DNA microarray analysis revealed approximately 3000 genes that were altered across all treatment groups (± 1.3 fold; p < 0.1). Several inflammatory mediators changed in a dose- and time-dependent manner at both the mRNA and protein level. Although no influx of neutrophils was detected at the low dose, changes in the expression of several genes and proteins associated with inflammation were observed. Resolving inflammation at the medium dose, and lack of neutrophil influx in the lung fluid at the low dose, were associated with down-regulation of genes involved in ion homeostasis and muscle regulation. Our gene expression results imply that retention of nano-TiO{sub 2} in the absence of inflammation over time may potentially perturb calcium and ion homeostasis, and affect smooth muscle activities. - Highlights: • Pulmonary effects following exposure to low doses of nano-TiO{sub 2} were examined. • Particle retention in lungs was assessed using nanoscale hyperspectral microscopy. • Particles persisted up to 28 days in lungs in all dose groups. • Inflammation was the pathway affected in the high dose group at all time points. • Ion homeostasis and muscle activity pathways were affected in the low dose

  17. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan

    2013-03-01

    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  18. Repeat prescribing: a role for community pharmacists in controlling and monitoring repeat prescriptions.

    OpenAIRE

    Bond, C.; Matheson, C.; Williams, S; Williams, P.; Donnan, P

    2000-01-01

    BACKGROUND: Traditional systems of managing repeat prescribing have been criticised for their lack of clinical and administrative controls. AIM: To compare a community pharmacist-managed repeat prescribing system with established methods of managing repeat prescribing. METHOD: A randomised controlled intervention study (19 general medical practices, 3074 patients, 62 community pharmacists). Patients on repeat medication were given sufficient three-monthly scripts, endorsed for monthly dispens...

  19. Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships

    Directory of Open Access Journals (Sweden)

    Thompson Sally

    2010-11-01

    Full Text Available Abstract Background To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy. Methods Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies and gabapentin (4 studies over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures and "change from baseline in seizure-free days over the last 28 days (SFD". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations. Results The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25 and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27. Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg in terms of SFD over the last 28 days. Conclusion In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.

  20. Repeated dose toxicity and relative potency of 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for induction of CYP1A1, CYP1A2 and thymic atrophy in female Harlan Sprague-Dawley rats.

    Science.gov (United States)

    Hooth, Michelle J; Nyska, Abraham; Fomby, Laurene M; Vasconcelos, Daphne Y; Vallant, Molly; DeVito, Michael J; Walker, Nigel J

    2012-11-15

    In this study we assessed the relative toxicity and potency of the chlorinated naphthalenes 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) and 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemicals were administered in corn oil:acetone (99:1) by gavage to female Harlan Sprague-Dawley rats at dosages of 0 (vehicle), 500, 1500, 5000, 50,000 and 500,000 ng/kg (PCN 66 and PCN 67) and 1, 3, 10, 100, and 300 ng/kg (TCDD) for 2 weeks. Histopathologic changes were observed in the thymus, liver and lung of TCDD treated animals and in the liver and thymus of PCN treated animals. Significant increases in CYP1A1 and CYP1A2 associated enzyme activity were observed in all animals exposed to TCDD, PCN 66 and PCN 67. Dose response modeling of CYP1A1, CYP1A2 and thymic atrophy gave ranges of estimated relative potencies, as compared to TCDD, of 0.0015-0.0072, for PCN 66 and 0.00029-0.00067 for PCN 67. Given that PCN 66 and PCN 67 exposure resulted in biochemical and histopathologic changes similar to that seen with TCDD, this suggests that they should be included in the WHO toxic equivalency factor (TEF) scheme, although the estimated relative potencies indicate that these hexachlorinated naphthalenes should not contribute greatly to the overall human body burden of dioxin-like activity.

  1. Validation of a track repeating algorithm for intensity modulated proton therapy: clinical cases study

    Science.gov (United States)

    Yepes, Pablo P.; Eley, John G.; Liu, Amy; Mirkovic, Dragan; Randeniya, Sharmalee; Titt, Uwe; Mohan, Radhe

    2016-04-01

    Monte Carlo (MC) methods are acknowledged as the most accurate technique to calculate dose distributions. However, due its lengthy calculation times, they are difficult to utilize in the clinic or for large retrospective studies. Track-repeating algorithms, based on MC-generated particle track data in water, accelerate dose calculations substantially, while essentially preserving the accuracy of MC. In this study, we present the validation of an efficient dose calculation algorithm for intensity modulated proton therapy, the fast dose calculator (FDC), based on a track-repeating technique. We validated the FDC algorithm for 23 patients, which included 7 brain, 6 head-and-neck, 5 lung, 1 spine, 1 pelvis and 3 prostate cases. For validation, we compared FDC-generated dose distributions with those from a full-fledged Monte Carlo based on GEANT4 (G4). We compared dose-volume-histograms, 3D-gamma-indices and analyzed a series of dosimetric indices. More than 99% of the voxels in the voxelized phantoms describing the patients have a gamma-index smaller than unity for the 2%/2 mm criteria. In addition the difference relative to the prescribed dose between the dosimetric indices calculated with FDC and G4 is less than 1%. FDC reduces the calculation times from 5 ms per proton to around 5 μs.

  2. Finding and Characterizing Repeats in Plant Genomes.

    Science.gov (United States)

    Nicolas, Jacques; Peterlongo, Pierre; Tempel, Sébastien

    2016-01-01

    Plant genomes contain a particularly high proportion of repeated structures of various types. This chapter proposes a guided tour of available software that can help biologists to look for these repeats and check some hypothetical models intended to characterize their structures. Since transposable elements are a major source of repeats in plants, many methods have been used or developed for this large class of sequences. They are representative of the range of tools available for other classes of repeats and we have provided a whole section on this topic as well as a selection of the main existing software. In order to better understand how they work and how repeats may be efficiently found in genomes, it is necessary to look at the technical issues involved in the large-scale search of these structures. Indeed, it may be hard to keep up with the profusion of proposals in this dynamic field and the rest of the chapter is devoted to the foundations of the search for repeats and more complex patterns. The second section introduces the key concepts that are useful for understanding the current state of the art in playing with words, applied to genomic sequences. This can be seen as the first stage of a very general approach called linguistic analysis that is interested in the analysis of natural or artificial texts. Words, the lexical level, correspond to simple repeated entities in texts or strings. In fact, biologists need to represent more complex entities where a repeat family is built on more abstract structures, including direct or inverted small repeats, motifs, composition constraints as well as ordering and distance constraints between these elementary blocks. In terms of linguistics, this corresponds to the syntactic level of a language. The last section introduces concepts and practical tools that can be used to reach this syntactic level in biological sequence analysis. PMID:26519414

  3. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola, E-mail: ola.hammarsten@clinchem.gu.se

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.

  4. Multiplexed Memory-Insensitive Quantum Repeaters

    CERN Document Server

    Collins, O A; Kennedy, T A B; Kuzmich, A

    2006-01-01

    Long-distance quantum communication via distant pairs of entangled quantum bits (qubits) is the first step towards technologies such as perfectly secure message transmission and distributed quantum computing. To date, the most promising proposals require quantum repeaters to mitigate the exponential decrease in communication rate due to optical fiber losses. However, quantum repeaters are exquisitely sensitive to the lifetimes of the memory elements they use. We propose a new approach based on a real-time hardware reconfiguration of multiplexed quantum nodes. This scheme should enable the construction of multiplexed quantum repeater networks that are largely insensitive to the coherence times of the quantum memory elements.

  5. The child accident repeater: a review.

    Science.gov (United States)

    Jones, J G

    1980-04-01

    The child accident repeater is defined as one who has at least three accidents that come to medical attention within a year. The accident situation has features in common with those of the child who has a single accident through simple "bad luck", but other factors predispose him to repeated injury. In the child who has a susceptible personality, a tendency for accident repetition may be due to a breakdown in adjustment to a stressful environment. Prevention of repeat accidents should involve the usual measures considered appropriate for all children as well as an attempt to provide treatment of significant maladjustment and modification of a stressful environment.

  6. A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan

    DEFF Research Database (Denmark)

    Adam, Ishag; Magzoub, Mamoun; Osman, Maha E;

    2006-01-01

    : seventy-three patients (39 and 34 in the fixed and the loose regimen of AS+SMP respectively) completed the 28-days of follow-up. On day 3; all patients in both groups were a parasitaemic but one patient in the fixed group of AS+SMP f was still febrile.Polymerase chain reaction genotyping adjusted cure...... of the patients. CONCLUSION: both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice....

  7. The Moral Maturity of Repeater Delinquents.

    Science.gov (United States)

    Petronio, Richard J.

    1980-01-01

    Differences in moral development (as conceived by Kohlberg) were examined in a sample of delinquent teenagers. The repeater group was not found, as had been hypothesized, to be lower on moral maturity than those who engaged in less delinquency. (GC)

  8. Star repeaters for fiber optic links.

    Science.gov (United States)

    McMahon, D H; Gravel, R L

    1977-02-01

    A star repeater combines the functions of a passive star coupler and a signal regenerating amplifier. By more effectively utilizing the light power radiated by a light emitting diode, the star repeater can, when used with small diameter channels, couple as much power to all receivers of a multiterminal link as would be coupled to the single receiver of a simple point-to-point link.

  9. Quantum Key Distribution over Probabilistic Quantum Repeaters

    CERN Document Server

    Amirloo, Jeyran; Majedi, A Hamed

    2010-01-01

    A feasible route towards implementing long-distance quantum key distribution (QKD) systems relies on probabilistic schemes for entanglement distribution and swapping as proposed in the work of Duan, Lukin, Cirac, and Zoller (DLCZ) [Nature 414, 413 (2001)]. Here, we calculate the conditional throughput and fidelity of entanglement for DLCZ quantum repeaters, by accounting for the DLCZ self-purification property, in the presence of multiple excitations in the ensemble memories as well as loss and other sources of inefficiency in the channel and measurement modules. We then use our results to find the generation rate of secure key bits for QKD systems that rely on DLCZ quantum repeaters. We compare the key generation rate per logical memory employed in the two cases of with and without a repeater node. We find the cross-over distance beyond which the repeater system outperforms the non-repeater one. That provides us with the optimum inter-node distancing in quantum repeater systems. We also find the optimal exci...

  10. Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects.

    Science.gov (United States)

    Reichen, Christian; Madhurantakam, Chaithanya; Hansen, Simon; Grütter, Markus G; Plückthun, Andreas; Mittl, Peer R E

    2016-01-01

    The armadillo repeat serves as a scaffold for the development of modular peptide-recognition modules. In order to develop such a system, three crystal structures of designed armadillo-repeat proteins with third-generation N-caps (YIII-type), four or five internal repeats (M-type) and second-generation C-caps (AII-type) were determined at 1.8 Å (His-YIIIM4AII), 2.0 Å (His-YIIIM5AII) and 1.95 Å (YIIIM5AII) resolution and compared with those of variants with third-generation C-caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N-cap and internal repeats M1 to M3 are indeed extremely similar, but the comparison reveals structural differences in internal repeats M4 and M5 and the C-cap. These differences are caused by long-range effects of the C-cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid-body movement of the C-terminal part impairs the regular arrangement of internal repeats that forms the putative peptide-binding site. The second-generation C-cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo-repeat-based peptide-recognition system. PMID:26894544

  11. Eye lens radiation exposure and repeated head CT scans: A problem to keep in mind

    International Nuclear Information System (INIS)

    Objectives: The deterministic character of radiation-induced cataract is being called into question, raising the possibility of a risk in patients, especially children, exposed to ionizing radiation in case of repeated head CT-scans. This study aims to estimate the eye lens doses of a pediatric population exposed to repeated head CTs and to assess the feasibility of an epidemiological study. Methods: Children treated for a cholesteatoma, who had had at least one CT-scan of the middle ear before their tenth birthday, were included. Radiation exposure has been assessed from medical records and telephone interviews. Results: Out of the 39 subjects contacted, 32 accepted to participate. A total of 76 CT-scans were retrieved from medical records. At the time of the interview (mean age: 16 years), the mean number of CT per child was 3. Cumulative mean effective and eye lens doses were 1.7 mSv and 168 mGy, respectively. Conclusion: A relatively high lens radiation dose was observed in children exposed to repeated CT-scans. Due to that exposure and despite the difficulties met when trying to reach patients’ families, a large scale epidemiological study should be performed in order to assess the risk of radiation-induced cataracts associated with repeated head CT.

  12. The reaction of lymphatic component of hemopoiesis to fractionated irradiation and repeated bone marrow transplantation

    International Nuclear Information System (INIS)

    Mice were repeatedly subjected to individual doses of 60Co-gamma rays at intervals of four days up to total doses of 3, 6, 9, 12, 15, 18, 21 and 24 Gy. Under these conditions, signs of partial adaptation of the lymphatic component of hemopoiesis to conditions of repeated irradiations were found in mice which were given transplants of 106 nuclear cells of syngenetic bone marrow after each irradiation. Systematic findings of statistically significant differences in the values of the lymphatic hemopoietic component parameters studied between bone marrow recipients and animals subjected only to repeated irradiations were recorded after 24th day of experiment in mice which received total doses of 21 and 24 Gy. A positive influence of repeated transplantations in bone marrow recipients became manifested in these experimental groups already upon withdrawals made on day 4 after the last irradiation. A quite pronounced increase in the values of the bone marrow recipients' lymphatic hemopoietic component studied was then recorded upon withdrawals made on day 9 after the last irradiation. (orig.)

  13. Tumorigenic responses from single or repeated inhalation exposures to relatively insoluble aerosols of Ce-144

    International Nuclear Information System (INIS)

    Human occupational or environmental inhalation exposures may involve repeated or chronic exposures, but most laboratory studies of inhaled radionuclides have involved single exposures. This study was designed to compare the biological effects of repeated inhalation exposures of dogs to a relatively insoluble form of 144Ce with existing data for singly-exposed dogs that had the same cumulative dose to the lungs two years after exposure. To date, the biological effects observed in these repeatedly-exposed dogs have been substantially different from those seen in singly-exposed dogs, particularly during the first 5 years after the initial exposure. Although pulmonary hemangiosarcoma was the prominent biological effect seen in singly-exposed dogs between 2 and 4 years after exposure, no lung tumors were seen during the 5 years after the first of the repeated exposures. This response plus other clinical observations are discussed in relation to the patterns of dose rate and cumulative dose for the different exposure conditions. (H.K.)

  14. Evaluation of averted doses to infants by tap water restrictions after the Fukushima Daiichi nuclear power plant accident

    International Nuclear Information System (INIS)

    There has been some concern in reviewing the effectiveness of making decisions on the implementation of protective measures in emergency exposure situations. After the Fukushima Daiichi nuclear power plant accident, temporal changes in the concentration of iodine 131 in tap water were studied using published data from several authorities in Fukushima, Ibaraki, and Tokyo. Averted doses to infants (1-year-old children) due to the intake of iodine 131 through tap water restrictions were also evaluated. Consequently, it was found that the apparent half-life of iodine 131 in tap water was 2.8 days. The averted equivalent doses to the thyroids of 1-year-old children were found to have a maximum value of 8.3 mSv in a local area of Fukushima. Hence, the tap water restrictions implemented by the authorities were considered to be effective in the early phase of the emergency exposure situation. (author)

  15. Evaluation of Radiographic Repeat Rate Data and Film Reject Analysis of Radiology Departments in Several Hospitals of Hamadan University of Medical Sciences

    OpenAIRE

    Simak Sabzevari; Karim Ghazikhanlou Sani

    2011-01-01

    Background/Objective: Rejected and repeated"nradiographies are one of the most frequent difficulties"nin radiography. The dose received by patients,"nequipment fault, costs and patients wait time increases"nby increasing film rejection and repeat rate. Moreover,"nthis leads to decreasing the care level because of the"ndelay in film report. This study aims to evaluate the"nfilm rejection and repeat rate in university-affiliated"nhospitals of Hamadan City...

  16. Haemopoiesis in murine bone marrow and spleen after fractionated irradiation and repeated bone marrow transplantation. II

    International Nuclear Information System (INIS)

    Granulopoiesis was studied in mice repeatedly exposed to doses of 3 Gy of 60Co γ-rays at 4-day intervals up to a total dose of 24 Gy on the basis of total bone marrow cellularity follow-up and analysis of myelograms and splenograms. Half the number of the mice received lO6 nuclear cells of syngeneic bone marrow after each fractional radiation dose. After an initial steep decrease, the number of granuloid cells in the spleen increased about 30-fold between days 12 and 16 of the experiment (total dose 9 and 12 Gy, respectively). This increase was temporary and between days 20 and 24 (total dose 15 and 18 Gy, respectively) a steep decrease again occurred. At a low level (below 10% of the control value) the granuloid cells remained in the spleens of bone marrow recipients until the end of the experiment (day 37, total dose 24 Gy). The behavior of the granuloid compartment of hemopoiesis thus contrasts with findings in the erythroid compartment (Hofer et al., 1989) when high numbers of erythroid nuclear cells remained in the spleens of bone marrow recipients until the end of the experiment. On the whole, the influence of repeated bone marrow transplantation on granulopoiesis in the bone marrow and spleen is positive. Of the 22 comparisons made between bone marrow recipients and mice only irradiated, 14 differences are statistically significant, always in favor of bone marrow recipients. (author)

  17. Repeated exposure to MDMA provides neuroprotection against subsequent MDMA-induced serotonin depletion in brain

    OpenAIRE

    Bhide, Nirmal S.; Lipton, Jack; Cunningham, Jacobi; Yamamoto, Bryan K.; Gudelsky, Gary A.

    2009-01-01

    Repeated exposure to sub-lethal insults has been reported to result in neuroprotection against a subsequent deleterious insult. The purpose of this study was to evaluate whether repeated exposure (preconditioning) to a non-5-HT depleting dose of MDMA in adult rats provides neuroprotection against subsequent MDMA induced 5-HT depletion. Treatment of rats with MDMA (10 mg/kg, ip every 2 hrs for 4 injections) resulted in a 50-65% depletion of 5-HT in the striatum, hippocampus and cortex, and the...

  18. 经皮反复给予玉红膏对大鼠器官毒性的研究%Organ toxicity of Yuhong Ointment(玉红膏) after repeated transdermal administration in rats

    Institute of Scientific and Technical Information of China (English)

    胡小靖; 孙新民; 黄雯; 邱恒; 牟稷征; 王丽霞; 王旗

    2013-01-01

    Objective To observe the effects of Yuhong Ointment on rat's liver and kidney functions and histomorphology of heart,brain,liver,kidney and spleen after transdermal administration repeatedly,in order to provide experimental evidences for safe use of Yuhong Ointment in clinical practice.Methods A total of 100 SPF SD rats of equal number of both genders,weighting 200 g,were divided into 5 groups:matrix control group,1 time concentration of Yuhong Ointment group (containing 0.4% calomel),2 times concentration of Yuhong Ointment group (containing 0.8% calomel),4 times concentration of Yuhong Ointment group (containing 1.6% calomel) and calomel group (containing 1.6% calomel) by drawn lots randomly,each group comprised 20 rats.The model of rat's skin injury was prepared.Yuhong Ointment in different concentrations were applied on the skin-impaired once daily for 28 days.The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),blood urea nitrogen (BUN),creatinine (Cr) and N-acetyl beta-D glucosaminidase (NAG) of rats in different groups were measured before treatment,14 and 28 days after treatment,and 28 days after drug withdrawal,respectively.Ten rats in every group were sacrificed on 28 days after treatment and 28 days after drug withdrawal,respectively.The heart,brain,liver,kidney,and spleen of rats in different groups were taken and weighed up.The organ coefficients were calculated and the histomorphological changes of liver,kidney and spleen were examined.Results There were no statistically significant differences in levels of serum ALT、AST、BUN、Cr and NAG in rats among the different concentrations of Yuhong Ointment groups,1.6% calomel group and matrix control group (all P > 0.05).The level of serum Cr in rat of 1.6% calomel group was significantly higher than that of matrix control group 28 days after drug withdrawal (P < 0.05).The kidney coefficients of rats in 2 times and 4 times concentration of Yuhong Ointment group and

  19. Enjebi Island dose assessment

    International Nuclear Information System (INIS)

    We have updeated the radiological dose assessment for Enjebi Island at Enewetak Atoll using data derived from analysis of food crops grown on Enjebi. This is a much more precise assessment of potential doses to people resettling Enjebi Island than the 1980 assessment in which there were no data available from food crops on Enjebi. Details of the methods and data used to evaluate each exposure pathway are presented. The terrestrial food chain is the most significant potential exposure pathway and 137Cs is the radionuclide responsible for most of the estimated dose over the next 50 y. The doses are calculated assuming a resettlement date of 1990. The average wholebody maximum annual estimated dose equivalent derived using our diet model is 166 mremy;the effective dose equivalent is 169 mremy. The estimated 30-, 50-, and 70-y integral whole-body dose equivalents are 3.5 rem, 5.1 rem, and 6.2 rem, respectively. Bone-marrow dose equivalents are only slightly higher than the whole-body estimates in each case. The bone-surface cells (endosteal cells) receive the highest dose, but they are a less sensitive cell population and are less sensitive to fatal cancer induction than whole body and bone marrow. The effective dose equivalents for 30, 50, and 70 y are 3.6 rem, 5.3 rem, and 6.6 rem, respectively. 79 refs., 17 figs., 24 tabs

  20. Quantum key distribution over probabilistic quantum repeaters

    Science.gov (United States)

    Amirloo, Jeyran; Razavi, Mohsen; Majedi, A. Hamed

    2010-09-01

    A feasible route toward implementing long-distance quantum key distribution (QKD) systems relies on probabilistic schemes for entanglement distribution and swapping as proposed in the work of Duan, Lukin, Cirac, and Zoller (DLCZ) [Nature (London)NATUAS0028-083610.1038/35106500 414, 413 (2001)]. Here, we calculate the conditional throughput and fidelity of entanglement for DLCZ quantum repeaters by accounting for the DLCZ self-purification property in the presence of multiple excitations in the ensemble memories as well as loss and other sources of inefficiency in the channel and measurement modules. We then use our results to find the generation rate of secure key bits for QKD systems that rely on DLCZ quantum repeaters. We compare the key generation rate per logical memory employed in the two cases with and without a repeater node. We find the crossover distance beyond which the repeater system outperforms the nonrepeater one. That provides us with the optimum internode distancing in quantum repeater systems. We also find the optimal excitation probability at which the QKD rate peaks. Such an optimum probability, in most regimes of interest, is insensitive to the total distance.

  1. Consuming a multi-ingredient thermogenic supplement for 28 days is apparently safe in healthy adults

    OpenAIRE

    Vogel, Roxanne M.; Jordan M. Joy; Falcone, Paul H.; Matt M. Mosman; Michael P Kim; Jordan R Moon

    2015-01-01

    Background: Thermogenic (TRM) supplements are often used by people seeking to decrease body weight. Many TRM supplements are formulated with multiple ingredients purported to increase energy expenditure and maximize fat loss. However, in the past some TRM ingredients have been deemed unsafe and removed from the market. Therefore, it is important to verify the safety of multi-ingredient TRM supplements with chronic consumption.Objective: To assess the safety of daily consumption of a multi-ing...

  2. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    Science.gov (United States)

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  3. Jet Fuel Kerosene is not Immunosuppressive in Mice or Rats Following Inhalation for 28 Days

    OpenAIRE

    White, Kimber L.; DeLorme, Michael P.; Beatty, Patrick W.; Smith, Matthew J; Peachee, Vanessa L.

    2013-01-01

    Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (...

  4. Registration of radiation doses

    International Nuclear Information System (INIS)

    In Finland the Radiation and Nuclear Safety Authority (STUK) is maintaining the register (called Dose Register) of the radiation exposure of occupationally exposed workers in order to ensure compliance with the principles of optimisation and individual protection. The guide contains a description of the Dose Register and specifies the responsibilities of the party running a radiation practice to report the relevant information to the Dose Register

  5. [Effect of dosed diet restriction on physiological remodeling and bioelectric properties of bone].

    Science.gov (United States)

    Levashov, M I; Ianko, R V; Chaka, E G; Safonov, S L

    2014-07-01

    The effect of dosed diet restriction on the physiological remodeling and bioelectric properties of bone tissue was studied in 48 male Wistar rats 3- and 18-months of age. The rate of bone tissue apposition was studied by the dynamic histomorphometry method (intravital tetracycline labeling). Electric potentials on the periosteal surface of the freshly isolated femurs were recorded. The magnitude of dielectric loss factor was determined to assess the quality of bone tissue. The control rats received a standard diet. The experimental rats received a limited diet (60 % of the standard mass) for 28 days. The magnitude and rate of the bone tissue apposition on the endosteal and periosteal surface of the tibia were less by 38.4% and 122.7% respectively in experimental rats after dosed diet restriction. Electric potential in the metaphyseal-epiphyseal growth zones of the femur was 29.7% lower, and the dielectric loss factor increased by 15.8%. The bone tissue apposition rate and the electric potential magnitude were increased 10 days after completion of the dosed diet restriction. The magnitude of the dielectric loss factor decreased after returning to the standard diet. Key words: dosed diet restriction, bone, remodelling, bioelectric properties. PMID:25669112

  6. Repeat surgery after failed midurethral slings

    DEFF Research Database (Denmark)

    Hansen, Margrethe Foss; Lose, Gunnar; Kesmodel, Ulrik Schiøler;

    2016-01-01

    MUS from 1998 through 2007. The outcome was repeat surgery with any subsequent procedure code for urinary incontinence within a 5-year period of the first procedure. RESULTS: A total of 5,820 women (mean age 55.4 years, ± 12.1) were registered with a synthetic MUS, and 354 (6 %) underwent reoperation...... they had undergone their primary synthetic MUS. CONCLUSION: In this nationwide cohort study of synthetic MUS a repeat synthetic MUS was the first choice and urethral injection therapy a frequent second choice. The majority of reoperations (82 %) took place in the same department as the primary operation....

  7. Repeating pneumatic pellet injector in JAERI

    International Nuclear Information System (INIS)

    A repeating pneumatic pellet injector has been developed and constructed at Japan Atomic Energy Research Institute. This injector can provide repetitive pellet injection to fuel tokamak plasmas for an extended period of time, aiming at the improvement of plasma performance. The pellets with nearly identical speed and mass can be repeatedly injected with a repetition rate of 2-3.3 Hz and a speed of up to 1.7 km/s by controlling the temperature of the cryogenic system, the piston speed and the pressure of the propellant gas. (author)

  8. Establishment of a dosimetric system for high doses using glasses

    International Nuclear Information System (INIS)

    A routine dosimetric system was developed using commercial glass samples. The dosimetric characteristics of national and imported samples were studied: batch uniformity, response repeatability, reutilization, absorbed dose response, detection range, response stability as a function of absorbed dose, storage temperature and thermal treatments pre- and post-irradiation, using the optical absorption technique. As an application, the dosimetric system was tested in a flower irradiation process at IPEN. All the obtained results show the usefulness of the proposed system for high dose dosimetry. (author)

  9. A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Erin Pettijohn

    2014-10-01

    Full Text Available Background: Temozolomide is efficacious as an oral alternative for patients with metastatic melanoma (MM. Calcitriol has anti-proliferative properties and vitamin D receptor (VDR polymorphisms are associated with alterations in melanoma susceptibility and progression. Methods: Tem 150 mg/m2 was administered on days 2–8 and 16–22 every 28 days. Calcitriol was given on days 1 and 15 every 28 days. VDR gene analysis was completed using PCR-RFLP based assays. Tolerability was the primary objective with secondary objectives of time to progression (TTP and overall survival (OS. Results: Twenty pts with MM were registered. Cytopenias and thrombosis were the most common grade 3 or 4 toxicities. Median TTP was 1.8 mo. Pts with high-risk VDR genotype tt+/−ff (n = 6 had an OS of 3.8 mo from time of enrollment, compared to 7.4 mo for those with non-tt/ff genotypes (n = 11, although not statistically significant (HR = 1.20, 95% CI 0.41–3.53, p = 0.74. Conclusions: The extended dosing of Tem with calcitriol is a well-tolerated regimen. The trend toward improved OS in non-tt/ff VDR genotypes is consistent with prior studies associating the tt/ff genotype with biologic aggressiveness.

  10. Copy number of tandem direct repeats within the inverted repeats of Marek's disease virus DNA.

    Science.gov (United States)

    Kanamori, A; Nakajima, K; Ikuta, K; Ueda, S; Kato, S; Hirai, K

    1986-12-01

    We previously reported that DNA of the oncogenic strain BC-1 of Marek's disease virus serotype 1 (MDV1) contains three units of tandem direct repeats with 132 base pair (bp) repeats within the inverted repeats of the long regions of the MDV1 genome, whereas the attenuated, nononcogenic viral DNA contains multiple units of tandem direct repeats (Maotani et al., 1986). In the present study, the difference in the copy numbers of 132 bp repeats of oncogenic and nononcogenic MDV1 DNAs in other strains of MDV1 was investigated by Southern blot hybridization. The main copy numbers in different oncogenic MDV1 strains differed: those of BC-1, JM and highly oncogenic Md5 were 3, 5 to 12 and 2, respectively. The viral DNA population with two units of repeats was small, but detectable, in cells infected with either the oncogenic BC-1 or JM strain. The MDV1 DNA in various MD cell lines contained either two units or both two and three units of repeats. The significance of the copy number of repeats in oncogenicity of MDV1 is discussed.

  11. Establishment of a dosimetric system for high doses using glasses; Estabelecimento de um sistema dosimetrico para doses altas utilizando vidros

    Energy Technology Data Exchange (ETDEWEB)

    Correa Quezada, Valeria de la Asuncion

    1997-07-01

    A routine dosimetric system was developed using commercial glass samples. The dosimetric characteristics of national and imported samples were studied: batch uniformity, response repeatability, reutilization, absorbed dose response, detection range, response stability as a function of absorbed dose, storage temperature and thermal treatments pre- and post-irradiation, using the optical absorption technique. As an application, the dosimetric system was tested in a flower irradiation process at IPEN. All the obtained results show the usefulness of the proposed system for high dose dosimetry. (author)

  12. Adaptation and complexity in repeated games

    DEFF Research Database (Denmark)

    Maenner, Eliot Alexander

    2008-01-01

    The paper presents a learning model for two-player infinitely repeated games. In an inference step players construct minimally complex inferences of strategies based on observed play, and in an adaptation step players choose minimally complex best responses to an inference. When players randomly ...

  13. Why Do Students Repeat Admissions Tests?

    Science.gov (United States)

    Jones, Martha S.

    Attitudes and beliefs about the admissions process, especially the role of standardized testing in admissions, were examined for students who took a standardized admissions test more than once. Their attitudes were compared with those of students who did not repeat the test. About 200 preveterinary students who had taken the Veterinary Aptitude…

  14. The Effect of Repeaters on Equating

    Science.gov (United States)

    Kim, HeeKyoung; Kolen, Michael J.

    2010-01-01

    Test equating might be affected by including in the equating analyses examinees who have taken the test previously. This study evaluated the effect of including such repeaters on Medical College Admission Test (MCAT) equating using a population invariance approach. Three-parameter logistic (3-PL) item response theory (IRT) true score and…

  15. Multivariate linear models and repeated measurements revisited

    DEFF Research Database (Denmark)

    Dalgaard, Peter

    2009-01-01

    Methods for generalized analysis of variance based on multivariate normal theory have been known for many years. In a repeated measurements context, it is most often of interest to consider transformed responses, typically within-subject contrasts or averages. Efficiency considerations leads...

  16. Triggering of repeating earthquakes in central California

    Science.gov (United States)

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  17. A Repeater in the Language Laboratory

    Science.gov (United States)

    Griffiths, B. T.

    1969-01-01

    Discusses the feasilility of the use of repeater devices in the language laboratory in order to enable the student to "recapitulate effortlessly and and indefinitely any utterance of any length which is causing him difficulty or is of special interest. (FWB)

  18. The Differential Effects of Repeating Kindergarten

    Science.gov (United States)

    Burkam, David T.; LoGerfo, Laura; Ready, Doug; Lee, Valerie E.

    2007-01-01

    We use the Early Childhood Longitudinal Study to investigate national patterns addressing (a) who repeats kindergarten, and (b) the subsequent cognitive effects of this event. Using OLS regression techniques, we investigate 1st-time kindergartners who are promoted, 1st-time kindergartners who are retained, and children who are already repeating…

  19. Childhood experiences and repeated suicidal behavior

    DEFF Research Database (Denmark)

    Krarup, Gertrud; Nielsen, Bent; Rask, P;

    1991-01-01

    that the psychological climate of the home may be more important than the rupture of early home life. It is noteworthy that the group of repeaters, as against the first-evers, could be characterized by personality disorders and abuse, especially of alcohol: disorders known to be precipitated by a discordant childhood...

  20. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-04-02

    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.  Created: 4/2/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/2/2013.

  1. Structural basis for triplet repeat disorders

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves;

    1999-01-01

    that approximately 150 bp is a general threshold length far repeat instability Since this is about the length of DNA wrapped up in a single nucleosome care particle, we speculate that chromatin structure may play an important role in the expansion mechanism. We furthermore suggest that expansion afa dodecamer repent...

  2. Costly renegotiation in repeated Bertand games

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2010-01-01

    This paper extends the concept of weak renegotiation-proof equilibrium (WRP) to allow for costly renegotiation and shows that even small renegotiation costs can have dramatic effects on the set of equilibria. More specifically, the paper analyzes the infinitely repeated Bertrand game. It is shown...

  3. Testing Multiple Outcomes in Repeated Measures Designs

    Science.gov (United States)

    Lix, Lisa M.; Sajobi, Tolulope

    2010-01-01

    This study investigates procedures for controlling the familywise error rate (FWR) when testing hypotheses about multiple, correlated outcome variables in repeated measures (RM) designs. A content analysis of RM research articles published in 4 psychology journals revealed that 3 quarters of studies tested hypotheses about 2 or more outcome…

  4. Repeater For A Digital-Communication Bus

    Science.gov (United States)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  5. On balanced minimal repeated measurements designs

    Directory of Open Access Journals (Sweden)

    Shakeel Ahmad Mir

    2014-10-01

    Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

  6. EVOLUTION AND RECOMBINATION OF BOVINE DNA REPEATS

    NARCIS (Netherlands)

    JOBSE, C; BUNTJER, JB; HAAGSMA, N; BREUKELMAN, HJ; BEINTEMA, JJ; LENSTRA, JA

    1995-01-01

    The history of the abundant repeat elements in the bovine genome has been studied by comparative hybridization and PCR. The Bov-A and Bov-B SINE elements both emerged just after the divergence of the Camelidae and the true ruminants. A 31-bp subrepeat motif in satellites of the Bovidae species cattl

  7. Critical metal blistering doses

    Energy Technology Data Exchange (ETDEWEB)

    Kalin, B.A.; Kirilin, N.M.; Pisarev, A.A.

    1975-08-01

    Critical He ion bombardment doses associated with blistering of Nb and stainless steel were measured. It was found that the critical doses for these materials are close together and in the range 1 to 4 x 10/sup 17/ ion/cm/sup 2/. (JRD)

  8. Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus.

    Science.gov (United States)

    Fan, Mingyue; Jin, Wei; Zhao, Haifeng; Xiao, Yining; Jia, Yanqiu; Yin, Yu; Jiang, Xin; Xu, Jing; Meng, Nan; Lv, Peiyuan

    2015-09-15

    Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression.

  9. Accuracy of velocities from repeated GPS measurements

    Science.gov (United States)

    Akarsu, V.; Sanli, D. U.; Arslan, E.

    2015-04-01

    Today repeated GPS measurements are still in use, because we cannot always employ GPS permanent stations due to a variety of limitations. One area of study that uses velocities/deformation rates from repeated GPS measurements is the monitoring of crustal motion. This paper discusses the quality of the velocities derived using repeated GPS measurements for the aim of monitoring crustal motion. From a global network of International GNSS Service (IGS) stations, we processed GPS measurements repeated monthly and annually spanning nearly 15 years and estimated GPS velocities for GPS baseline components latitude, longitude and ellipsoidal height. We used web-based GIPSY for the processing. Assuming true deformation rates can only be determined from the solutions of 24 h observation sessions, we evaluated the accuracy of the deformation rates from 8 and 12 h sessions. We used statistical hypothesis testing to assess the velocities derived from short observation sessions. In addition, as an alternative control method we checked the accuracy of GPS solutions from short observation sessions against those of 24 h sessions referring to statistical criteria that measure the accuracy of regression models. Results indicate that the velocities of the vertical component are completely affected when repeated GPS measurements are used. The results also reveal that only about 30% of the 8 h solutions and about 40% of 12 h solutions for the horizontal coordinates are acceptable for velocity estimation. The situation is much worse for the vertical component in which none of the solutions from campaign measurements are acceptable for obtaining reliable deformation rates.

  10. Dose response relationship at low doses

    International Nuclear Information System (INIS)

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

  11. 47 CFR 80.1179 - On-board repeater limitations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false On-board repeater limitations. 80.1179 Section... On-board repeater limitations. When an on-board repeater is used, the following limitations must be met: (a) The on-board repeater antenna must be located no higher than 3 meters (10 feet) above...

  12. BNCT and dose fractionation

    International Nuclear Information System (INIS)

    Some portion of the radiation dose received by a patient during BNCT consists of primary and secondary gammas. The biological effect of that portion of the dose will depend upon the time history of the delivered dose. The well-known models for relating time-dose effects to clinical experience, are of questionable value in understanding dose effects in the time regime of a few hours, and for doses of less than tolerance. In order to examine the time-dose effect in the regime of interest to BNCT a simple phenomenological model was developed and normalized to the accepted body of clinical experience. The model has been applied to the question of fractionation of BNCT and the results are presented. The model is simply a linear healing model with two time constants. In other words, a first hit of radiation is assumed to wound (or potentiate) a cell. Given time, the cell will fully repair itself. If a second hit occurs before the cell has healed, the cell is killed. Apparently, there are two kinds of healing, one which occurs in 30 to 60 minutes, the other in two to four days. A small fraction of the cells will die on the first hit

  13. Haemopoiesis in murine bone marrow and spleen after fractionated irradiation and repeated bone marrow transplantation. I

    International Nuclear Information System (INIS)

    Erythropoiesis was studied in mice repeatedly exposed to doses of 3 Gy of 60Co γ-rays at 4-day intervals up to a total dose of 24 Gy on the basis of total bone marrow and spleen cellularity follow-up and analysis of myelograms and splenograms. Half the number of the mice received 106 nuclear cells of syngeneic bone marrow after each fractional radiation dose. It was mainly the spleen which was involved in the adaptation and regeneration of erythropoiesis, its contribution to total erythropoiesis in bone marrow recipients having been as high as 73.9% (day 20 of experiment, total dose 15 Gy). In mice only irradiated, the number of nuclear cells of erythroid lineage decreased to zero values sooner in the spleen (day 16 of experiment, total dose 12 Gy) than in the bone marrow (day 24 of experiment, total dose 18 Gy). The analysis of the results of collections made on day 9 after the last irradiation revealed, however, that the hemopoietic microenvironment of the spleen and hemopoietic cells capable of differentiation in the erythroid direction were so resistant to irradiation in mice only irradiated that erythropoiesis in their spleens exhibited signs of regeneration even after the highest total dose of 24 Gy. (author). 2 figs., 3 tabs., 12 refs

  14. Absorption, distribution, metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats

    DEFF Research Database (Denmark)

    Löschner, Katrin; Hadrup, Niels; Hansen, Marianne;

    2014-01-01

    A suspension of nanoparticles of BSA-stabilized red amorphous elemental selenium (Se) or an aqueous solution of sodium selenite was repeatedly administered by oral gavage for 28 days at 0.05 mg/kg bw/day (low dose) or at 0.5 mg/kg bw/day (high dose) as Se to female rats. Prior to administration, ...

  15. Nonparametric additive regression for repeatedly measured data

    KAUST Repository

    Carroll, R. J.

    2009-05-20

    We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements. We allow for a working covariance matrix for the regression errors, showing that our method is most efficient when the correct covariance matrix is used. The component functions achieve the known asymptotic variance lower bound for the scalar argument case. Smooth backfitting also leads directly to design-independent biases in the local linear case. Simulations show our estimator has smaller variance than the usual kernel estimator. This is also illustrated by an example from nutritional epidemiology. © 2009 Biometrika Trust.

  16. High-bandwidth hybrid quantum repeater.

    Science.gov (United States)

    Munro, W J; Van Meter, R; Louis, Sebastien G R; Nemoto, Kae

    2008-07-25

    We present a physical- and link-level design for the creation of entangled pairs to be used in quantum repeater applications where one can control the noise level of the initially distributed pairs. The system can tune dynamically, trading initial fidelity for success probability, from high fidelity pairs (F=0.98 or above) to moderate fidelity pairs. The same physical resources that create the long-distance entanglement are used to implement the local gates required for entanglement purification and swapping, creating a homogeneous repeater architecture. Optimizing the noise properties of the initially distributed pairs significantly improves the rate of generating long-distance Bell pairs. Finally, we discuss the performance trade-off between spatial and temporal resources.

  17. Repeated interactions in open quantum systems

    International Nuclear Information System (INIS)

    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium

  18. Repeated interactions in open quantum systems

    Energy Technology Data Exchange (ETDEWEB)

    Bruneau, Laurent, E-mail: laurent.bruneau@u-cergy.fr [Laboratoire AGM, Université de Cergy-Pontoise, Site Saint-Martin, BP 222, 95302 Cergy-Pontoise (France); Joye, Alain, E-mail: Alain.Joye@ujf-grenoble.fr [Institut Fourier, UMR 5582, CNRS-Université Grenoble I, BP 74, 38402 Saint-Martin d’Hères (France); Merkli, Marco, E-mail: merkli@mun.ca [Department of Mathematics and Statistics Memorial University of Newfoundland, St. John' s, NL Canada A1C 5S7 (Canada)

    2014-07-15

    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium.

  19. Learning With Repeated-Game Strategies

    Directory of Open Access Journals (Sweden)

    Christos A. Ioannou

    2014-07-01

    Full Text Available We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2x2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we fi□nd that the strategy with the most occurrences is the Grim-Trigger. In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the Win-Stay, Lose-Shift and Grim-Trigger strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes.

  20. Radiation dose to the eye lens

    DEFF Research Database (Denmark)

    Baun, Christina; Falch Braas, Kirsten; D. Nielsen, Kamilla;

    2015-01-01

    might avoid including the eye in the CT scan without losing sufficient visualization of the scull base. The aim of this study was to evaluate the possibility of decreasing the radiation dose to the eye lens, simply by changing the head position, when doing the PET/CT scan from the base of the scull...... to the proximal femur. Methods and materials: The study was performed using a human like whole body phantom with electronic dosimetry units placed upon each eye to detect the exact radiation dose to the eye lens during each scan. The phantom’s head was placed in two different positions, (a) elevated with a small...... pillow below the head (standard), and (b) kipped backwards with the pillow below the neck (kipped). For each head position, CT scans were repeated 5 times with both a low dose and a high dose CT protocol; in this way, a total of 20 CT scans were performed. Robust standard errors were used in order...

  1. Repeated extraction of DNA from FTA cards

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus;

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible...... to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range....

  2. Repeatability of Response to Asthma Medications

    Science.gov (United States)

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  3. Repeatability and Workability Evaluation of SIGMOD 2011

    DEFF Research Database (Denmark)

    Bonnet, Philippe

    2011-01-01

    SIGMOD has offered, since 2008, to verify the experiments published in the papers accepted at the conference. This year, we have been in charge of reproducing the experiments provided by the authors (repeatability), and exploring changes to experiment parameters (workability). In this paper, we a...... find that most experiments are distributed as Linux packages accompanied by instructions on how to setup and run the experiments. We are still far from the vision of executable papers...

  4. Aging and Repeated Thought Suppression Success

    OpenAIRE

    Ann E Lambert; Smyth, Frederick L.; Jessica R Beadel; Teachman, Bethany A.

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differe...

  5. Repeat Gamma Knife surgery for vestibular schwannomas

    OpenAIRE

    Sarah Lonneville; Carine Delbrouck; Cécile Renier; Daniel Devriendt; Nicolas Massager

    2015-01-01

    Background: Gamma Knife (GK) surgery is a recognized treatment option for the management of small to medium-sized vestibular schwannoma (VS) associated with high-tumor control and low morbidity. When a radiosurgical treatment fails to stop tumor growth, repeat GK surgery can be proposed in selected cases. Methods : A series of 27 GK retreatments was performed in 25 patients with VS; 2 patients underwent three procedures. The median time interval between GK treatments was 45 months. The me...

  6. Repeated extraction of DNA from FTA cards

    OpenAIRE

    Stangegaard, Michael; Ferrero, Laura; Børsting, Claus; Frank-Hansen, Rune; Hansen, Anders Johannes; Morling, Niels

    2011-01-01

    Extraction of DNA using magnetic bead based techniques on automated DNA extraction instruments provides a fast, reliable and reproducible method for DNA extraction from various matrices. However, the yield of extracted DNA from FTA-cards is typically low. Here, we demonstrate that it is possible to repeatedly extract DNA from the processed FTA-disk. The method increases the yield from the nanogram range to the microgram range.

  7. Capacities of repeater-assisted quantum communications

    OpenAIRE

    Pirandola, Stefano

    2016-01-01

    We establish the ultimate rates for transmitting quantum information, distilling entanglement, and distributing secret keys in repeater-assisted quantum communications, under the most fundamental decoherence models for both discrete and continuous variable systems, including lossy channels, quantum-limited amplifiers, dephasing and erasure channels. These capacities are derived considering the most general adaptive protocols for quantum and private communication between the two end-points of ...

  8. Repeated Optional Gambles and Risk Aversion

    OpenAIRE

    Christian Gollier

    1996-01-01

    We analyze in this paper the effect of age on the optimal dynamic strategy toward repeated independent gambles. When deciding to accept or to reject a lottery that is offered today, the gambler knows how many lotteries can yet be played in the future. We first characterize the optimal dynamic strategy when future lotteries are identically distributed. We show that the existence of future lotteries always increases the willingness to gamble today. When the sequence of lotteries is independent ...

  9. Quantum Key Distribution over Probabilistic Quantum Repeaters

    OpenAIRE

    Amirloo, Jeyran; Razavi, Mohsen; Majedi, A. Hamed

    2010-01-01

    A feasible route towards implementing long-distance quantum key distribution (QKD) systems relies on probabilistic schemes for entanglement distribution and swapping as proposed in the work of Duan, Lukin, Cirac, and Zoller (DLCZ) [Nature 414, 413 (2001)]. Here, we calculate the conditional throughput and fidelity of entanglement for DLCZ quantum repeaters, by accounting for the DLCZ self-purification property, in the presence of multiple excitations in the ensemble memories as well as loss a...

  10. Radiation dose in vertebroplasty

    Energy Technology Data Exchange (ETDEWEB)

    Mehdizade, A.; Lovblad, K.O.; Wilhelm, K.E.; Somon, T.; Wetzel, S.G.; Kelekis, A.D.; Yilmaz, H.; Abdo, G.; Martin, J.B.; Viera, J.M.; Ruefenacht, D.A. [Neuroradiology DRRI, Geneva University Hospital, Rue Micheli-du-Crest 24, 1211, Geneva 14 (Switzerland)

    2004-03-01

    We wished to measure the absorbed radiation dose during fluoroscopically controlled vertebroplasty and to assess the possibility of deterministic radiation effects to the operator. The dose was measured in 11 consecutive procedures using thermoluminescent ring dosimeters on the hand of the operator and electronic dosimeters inside and outside of the operator's lead apron. We found doses of 0.022-3.256 mGy outside and 0.01-0.47 mGy inside the lead apron. Doses on the hand were higher, 0.5-8.5 mGy. This preliminary study indicates greater exposure to the operator's hands than expected from traditional apron measurements. (orig.)

  11. Controllable dose; Dosis controlable

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J.T.; Anaya M, R.A. [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico)]. E-mail: jtar@nuclear.inin.mx

    2004-07-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  12. Multiplexing schemes for quantum repeater networks

    Science.gov (United States)

    Aparicio, Luciano; Van Meter, Rodney

    2011-08-01

    When built, quantum repeaters will allow the distribution of entangled quantum states across large distances, playing a vital part in many proposed quantum technologies. Enabling multiple users to connect through the same network will be key to their real-world deployment. Previous work on repeater technologies has focussed only on simple entanglment production, without considering the issues of resource scarcity and competition that necessarily arise in a network setting. In this paper we simulated a thirteen-node network with up to five flows sharing different parts of the network, measuring the total throughput and fairness for each case. Our results suggest that the Internet-like approach of statistical multiplexing use of a congested link gives the highest aggregate throughput. Time division multiplexing and buffer space multiplexing were slightly less effective, but all three schemes allow the sum of multiple flows to substantially exceed that of any one flow, improving over circuit switching by taking advantage of resources that are forced to remain idle in circuit switching. All three schemes proved to have excellent fairness. The high performance, fairness and simplicity of implementation support a recommendation of statistical multiplexing for shared quantum repeater networks.

  13. Measuring pacemaker dose: A clinical perspective

    Energy Technology Data Exchange (ETDEWEB)

    Studenski, Matthew T., E-mail: matthew.studenski@jeffersonhospital.org [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Xiao Ying; Harrison, Amy S. [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

    2012-07-01

    Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired.

  14. Gonadal doses from radiotherapy

    International Nuclear Information System (INIS)

    The method of calculation of gonadal doses arising from different radiotherapeutic procedures is described. The measurement of scatter factors to the gonads from superficial and deep therapy is detailed and the analytic fits to the experimental data, as a function of field position, field size and beam energy are given. The data used to calculate the gonadal doses from treatments using linear accelerators, teletherapy and sealed sources are described and the analytic fits to the data given

  15. Effects of low doses

    International Nuclear Information System (INIS)

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

  16. Dose-dependent effects of a soluble dietary fibre (pectin on food intake, adiposity, gut hypertrophy and gut satiety hormone secretion in rats.

    Directory of Open Access Journals (Sweden)

    Clare L Adam

    Full Text Available Soluble fermentable dietary fibre elicits gut adaptations, increases satiety and potentially offers a natural sustainable means of body weight regulation. Here we aimed to quantify physiological responses to graded intakes of a specific dietary fibre (pectin in an animal model. Four isocaloric semi-purified diets containing 0, 3.3%, 6.7% or 10% w/w apple pectin were offered ad libitum for 8 or 28 days to young adult male rats (n = 8/group. Measurements were made of voluntary food intake, body weight, initial and final body composition by magnetic resonance imaging, final gut regional weights and histology, and final plasma satiety hormone concentrations. In both 8- and 28-day cohorts, dietary pectin inclusion rate was negatively correlated with food intake, body weight gain and the change in body fat mass, with no effect on lean mass gain. In both cohorts, pectin had no effect on stomach weight but pectin inclusion rate was positively correlated with weights and lengths of small intestine and caecum, jejunum villus height and crypt depth, ileum crypt depth, and plasma total glucagon-like peptide-1 (GLP-1 and peptide tyrosine tyrosine (PYY concentrations, and at 8 days was correlated with weight and length of colon and with caecal mucosal depth. Therefore, the gut's morphological and endocrine adaptations were dose-dependent, occurred within 8 days and were largely sustained for 28 days during continued dietary intervention. Increasing amounts of the soluble fermentable fibre pectin in the diet proportionately decreased food intake, body weight gain and body fat content, associated with proportionately increased satiety hormones GLP-1 and PYY and intestinal hypertrophy, supporting a role for soluble dietary fibre-induced satiety in healthy body weight regulation.

  17. Sequential morphologic analysis of the nephrotoxicity produced in rats by single doses of chlorozotocin.

    Science.gov (United States)

    Dees, J H; Kramer, R A

    1986-01-01

    Chlorozotocin is a chloroethylnitrosourea antitumor agent that is in clinical trial for a variety of human tumors. Renal failure has been a reported side effect of treatment with several of the chloroethylnitrosoureas, including chlorozotocin. To better understand the pathogenesis of this target organ toxicity, we have studied the nephrotoxicity of a single high, intermediate, or low dose of chlorozotocin in male F344 rats. We report here the sequence of histopathologic changes seen over a 1-10-day (high dose) or 1-28-day (intermediate or low dose) period. The single high dose (40 mg/kg, s.c.) produced an acute cortical necrosis involving the proximal tubules, followed by later necrotic changes in the collecting ducts in the inner medulla. Karyomegaly was noted at 10 days in occasional cells of the papillary collecting ducts and urinary epithelium lining the papilla. A single intermediate dose (25 mg/kg, s.c.) caused a similar but less severe injury of later onset. Proximal tubule injury was less severe and more limited. Necrosis of papillary collecting ducts was not seen; however, karyomegaly was pronounced in cells of the collecting ducts in the inner stripe of the outer medulla and inner medulla, and in the urinary epithelium covering the papilla. No discernible histopathology was present following the low dose (12.5 mg/kg, s.c.) of chlorozotocin. The histopathology was correlated with biochemical parameters. Our findings have possible implications for monitoring the severity of nephrotoxic side effects in patients, as well as provide preliminary evidence that this antineoplastic agent may itself cause preneoplastic changes, a finding with important long term implications.

  18. A Complete and Accurate Ab Initio Repeat Finding Algorithm.

    Science.gov (United States)

    Lian, Shuaibin; Chen, Xinwu; Wang, Peng; Zhang, Xiaoli; Dai, Xianhua

    2016-03-01

    It has become clear that repetitive sequences have played multiple roles in eukaryotic genome evolution including increasing genetic diversity through mutation, changes in gene expression and facilitating generation of novel genes. However, identification of repetitive elements can be difficult in the ab initio manner. Currently, some classical ab initio tools of finding repeats have already presented and compared. The completeness and accuracy of detecting repeats of them are little pool. To this end, we proposed a new ab initio repeat finding tool, named HashRepeatFinder, which is based on hash index and word counting. Furthermore, we assessed the performances of HashRepeatFinder with other two famous tools, such as RepeatScout and Repeatfinder, in human genome data hg19. The results indicated the following three conclusions: (1) The completeness of HashRepeatFinder is the best one among these three compared tools in almost all chromosomes, especially in chr9 (8 times of RepeatScout, 10 times of Repeatfinder); (2) in terms of detecting large repeats, HashRepeatFinder also performed best in all chromosomes, especially in chr3 (24 times of RepeatScout and 250 times of Repeatfinder) and chr19 (12 times of RepeatScout and 60 times of Repeatfinder); (3) in terms of accuracy, HashRepeatFinder can merge the abundant repeats with high accuracy. PMID:26272474

  19. Beneficial and adverse effects of irradiation in patients repeatedly subjected to high-dosage treatment

    International Nuclear Information System (INIS)

    During the period between 1978 and 1983 a total of 156 patients showing different types of tumours were subjected to high-dosage radiotherapy. The patients were treated repeatedly for primary or recurrent tumours using a radiation dose of >79 Gy. Each of the three largest groups, which were mammary carcinomas (33), cerebral tumours (25) and orohypopharyngeal tumours (22), was analysed individually. In the majority of patients the local effects of this radiotherapy were such that total or at least partial remission of the primary or recurrent tumour appeared most likely. In the groups receiving doses in the lower range the results were just as good as those achieved in subjects exposed to high doses. The survival times determined here for bearers of mammary or cerebral carcinomas were better than the relevant values given in the literature. (orig./MG)

  20. Comparison of creatine monohydrate and carbohydrate supplementation on repeated jump height performance.

    Science.gov (United States)

    Koenig, Chad A; Benardot, Dan; Cody, Mildred; Thompson, Walter R

    2008-07-01

    Creatine monohydrate (CrMH) supplementation aids the ability to maintain performance during repeated bouts of high-intensity exercise, including jump performance. However, carbohydrate supplementation may also provide similar benefits and is less expensive. This study compared the effects of an energy-free placebo, 2 different caloric concentrations of carbohydrate drinks, and a CrMH supplement on repeated jump heights. Sixty active males (mean age, 22 +/- 3.2 years) performed 2 sets of countermovement static jump height tests (10 jumps over 60 seconds) separated by 5 days to determine the differential effects of the placebo, carbohydrate, and CrMH on jump height sustainability over 10 jumps. Subjects were randomly assigned to groups (15 subjects per group) to receive daily doses (x5 days) of carbohydrate drinks containing 100 or 250 kilocalories (kcal), a 25-g CrMH supplement, or an energy-free placebo. After 5 days, the CrMH group experienced a significant weight gain (+1.52; +/-0.89 kg, p energy-free placebo over the final 3-4 jumps. The 250-kcal carbohydrate-supplemented group experienced a level of benefit (p < 0.01) that was at least equal to that of the CrMH group (p < 0.05), suggesting that the higher dose of carbohydrate was as effective as CrMH in maintaining repeated bouts of high-intensity activity as measured by repeated static jumps. Given the equivalent performance improvement and the absence of weight gain, the carbohydrate supplementation could be considered the preferred option for weight-conscious power athletes involved in activities that require repeated- motion high-intensity activities.

  1. Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice.

    Science.gov (United States)

    Thelen, Connor; Sens, Jonathon; Mauch, Joseph; Pandit, Radhika; Pitychoutis, Pothitos M

    2016-10-01

    One of the most striking discoveries in the treatment of major depression was the finding that infusion of a single sub-anesthetic dose of ketamine induces rapid and sustained antidepressant effects in treatment-resistant depressed patients. However, ketamine's antidepressant-like actions are transient and can only be sustained by repeated drug treatment. Despite the fact that women experience major depression at roughly twice the rate of men, research regarding the neurobiological antidepressant-relevant effects of ketamine has focused almost exclusively on the male sex. Importantly, knowledge regarding the sex-differentiated effects, the frequency and the dose on which repeated ketamine administration stops being beneficial, is limited. In the current study, we investigated the behavioral, neurochemical and synaptic molecular effects of repeated ketamine treatment (10mg/kg; 21days) in male and female C57BL/6J mice. We report that ketamine induced beneficial antidepressant-like effects in male mice, but induced both anxiety-like (i.e., decreased time spent in the center of the open field arena) and depressive-like effects (i.e., enhanced immobility duration in the forced swim test; FST) in their female counterparts. Moreover, repeated ketamine treatment induced sustained sex-differentiated neurochemical and molecular effects, as it enhanced hippocampal synapsin protein levels and serotonin turnover in males, but attenuated glutamate and aspartate levels in female mice. Taken together, our findings indicate that repeated ketamine treatment induces opposite behavioral effects in male and female mice, and thus, present data have far-reaching implications for the sex-oriented use of ketamine in both experimental and clinical research settings. PMID:27343934

  2. Utirik Atoll Dose Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Robison, W.L.; Conrado, C.L.; Bogen, K.T

    1999-10-06

    On March 1, 1954, radioactive fallout from the nuclear test at Bikini Atoll code-named BRAVO was deposited on Utirik Atoll which lies about 187 km (300 miles) east of Bikini Atoll. The residents of Utirik were evacuated three days after the fallout started and returned to their atoll in May 1954. In this report we provide a final dose assessment for current conditions at the atoll based on extensive data generated from samples collected in 1993 and 1994. The estimated population average maximum annual effective dose using a diet including imported foods is 0.037 mSv y{sup -1} (3.7 mrem y{sup -1}). The 95% confidence limits are within a factor of three of their population average value. The population average integrated effective dose over 30-, 50-, and 70-y is 0.84 mSv (84, mrem), 1.2 mSv (120 mrem), and 1.4 mSv (140 mrem), respectively. The 95% confidence limits on the population-average value post 1998, i.e., the 30-, 50-, and 70-y integral doses, are within a factor of two of the mean value and are independent of time, t, for t > 5 y. Cesium-137 ({sup 137}Cs) is the radionuclide that contributes most of this dose, mostly through the terrestrial food chain and secondarily from external gamma exposure. The dose from weapons-related radionuclides is very low and of no consequence to the health of the population. The annual background doses in the U. S. and Europe are 3.0 mSv (300 mrem), and 2.4 mSv (240 mrem), respectively. The annual background dose in the Marshall Islands is estimated to be 1.4 mSv (140 mrem). The total estimated combined Marshall Islands background dose plus the weapons-related dose is about 1.5 mSv y{sup -1} (150 mrem y{sup -1}) which can be directly compared to the annual background effective dose of 3.0 mSv y{sup -1} (300 mrem y{sup -1}) for the U. S. and 2.4 mSv y{sup -1} (240 mrem y{sup -1}) for Europe. Moreover, the doses listed in this report are based only on the radiological decay of {sup 137}Cs (30.1 y half-life) and other

  3. Deriving adaptive MRF coefficients from previous normal-dose CT scan for low-dose image reconstruction via penalized weighted least-squares minimization

    OpenAIRE

    Zhang, Hao; Han, Hao; Wang, Jing; Ma, Jianhua; Liu, Yan; Moore, William; Liang, Zhengrong

    2014-01-01

    Purpose: Repeated computed tomography (CT) scans are required for some clinical applications such as image-guided interventions. To optimize radiation dose utility, a normal-dose scan is often first performed to set up reference, followed by a series of low-dose scans for intervention. One common strategy to achieve the low-dose scan is to lower the x-ray tube current and exposure time (mAs) or tube voltage (kVp) setting in the scanning protocol, but the resulted image quality by the conventi...

  4. The effects of multiple UV exposures on HIV-LTR (long terminal repeat) expression

    International Nuclear Information System (INIS)

    Previous studies have shown that cellular stress agents such as UV radiation induce transcription from the long terminal repeat (LTR) of the human immunodeficiency virus (HIV). Using HeLa cells stably transfected with the HIV-LTR sequence, which transcriptionally drives the chloramphenicol acetyl transferase (CAT) reporter gene, we examined the effects of multiple exposures to UVC (254 nm) on HIV-LTR-CAT expression. Low doses (≤ 5 J m-2) had no effect on CAT expression, but up to 29-fold induction was observed with 10 J m-2 when cells were harvested 48 h after completion of the exposure. Little difference was noted in induction levels when cells were exposed to one 25 J m-2 dose, viable cells were harvested at 24 h, 48 h or 72 h, and cell lysates were assayed for CAT expression. Two sequential 12.5 J m-2 exposures, given 24 h apart, resulted in an additive effect on CAT expression; these two exposures produced CAT activity equivalent to that induced following a single 25 J m-2 dose. Our data suggest that HIV-LTR requires a specific threshold UV dose in order to elicit induction; a maximal induction dose is also evident; exposures higher than this maximal dose contribute no more to HIV-LTR induction in viable cells. (author)

  5. Repeated vitrification/warming of human sperm gives better results than repeated slow programmable freezing

    Institute of Scientific and Technical Information of China (English)

    Teraporn Vutyavanich; Worashorn Lattiwongsakorn; Waraporn Piromlertamorn; Sudarat Samchimchom

    2012-01-01

    In this study,we compared the effects of repeated freezing/thawing of human sperm by our in-house method of rapid freezing with slow programmable freezing.Sperm samples from 11 normozoospermic subjects were processed through density gradients and divided into three aliquots:non-frozen,rapid freezing and slow programmable freezing.Sperm in the rapid freezing group had better motility and viability than those in the slow freezing group (P<O.01) after the first,second and third cycles of freezing/thawing,but there was no difference in morphology.In the second experiment,rapid freezing was repeated three times in 20 subjects.The samples from each thawing cycle were evaluated for DNA fragmentation using the alkaline comet assay.DNA fragmentation began to increase considerably after the second cycle of freezing/thawing,but to a level that was not clinically important.In the third experiment,rapid freezing was done repeatedly in 10 subjects,until no motile sperm were observed after thawing.The median number of repeated freezing/thawing that yielded no motile sperm was seven (range:5-8,mean:6.8).In conclusion,we demonstrated that repeated freezing/thawing of processed semen using our rapid freezing method gave better results than standard slow programmable freezing.This method can help maximize the usage of precious cryopreserved sperm samples in assisted reproduction technology.

  6. A tandem repeat gene in a picornavirus.

    OpenAIRE

    Forss, S; Schaller, H

    1982-01-01

    Three closely related genes for the small genome-linked protein (VPg) of picornaviruses have been identified by sequence analysis as a tandem repeat in the genome of Foot and Mouth Disease Virus (FMDV), strain O1K. This unusual structure was also found in the genome of strain C1O, belonging to a different FMDV serotype. Predicted biochemical properties of the three VPg gene products are in excellent agreement with the data from protein analysis of a heterogeneous VPg population from a third F...

  7. Source coding model for repeated snapshot imaging

    CERN Document Server

    Li, Junhui; Yang, Dongyue; wu, Guohua; Yin, Longfei; Guo, Hong

    2016-01-01

    Imaging based on successive repeated snapshot measurement is modeled as a source coding process in information theory. The necessary number of measurement to maintain a certain level of error rate is depicted as the rate-distortion function of the source coding. Quantitative formula of the error rate versus measurement number relation is derived, based on the information capacity of imaging system. Second order fluctuation correlation imaging (SFCI) experiment with pseudo-thermal light verifies this formula, which paves the way for introducing information theory into the study of ghost imaging (GI), both conventional and computational.

  8. Mechanical processes with repeated attenuated impacts

    CERN Document Server

    Nagaev, R F

    1999-01-01

    This book is devoted to considering in the general case - using typical concrete examples - the motion of machines and mechanisms of impact and vibro-impact action accompanied by a peculiar phenomenon called "impact collapse". This phenomenon is that after the initial collision, a sequence of repeated gradually quickening collisions of decreasing-to-zero intensity occurs, with the final establishment of protracted contact between the interacting bodies. The initiation conditions of the impact collapse are determined and calculation techniques for the quantitative characteristics of the corresp

  9. Platelet peripheral benzodiazepine receptors in repeated stress

    Energy Technology Data Exchange (ETDEWEB)

    Dar, D.E.; Bidder, M.; Gavish, M. (Technion-Israel Institute of Technology, Haifa (Israel)); Weizman, A.; Karp, L.; Tyano, S. (Tel Aviv Univ. (Israel)); Grinshpoon, A.; Bleich, A.

    1991-01-01

    ({sup 3}H)PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.

  10. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Greiff Lennart

    2012-06-01

    Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

  11. Assessment of internal doses

    CERN Document Server

    Rahola, T; Falk, R; Isaksson, M; Skuterud, L

    2002-01-01

    There is a definite need for training in dose calculation. Our first course was successful and was followed by a second, both courses were fully booked. An example of new tools for software products for bioassay analysis and internal dose assessment is the Integrated Modules for Bioassay Analysis (IMBA) were demonstrated at the second course. This suite of quality assured code modules have been adopted in the UK as the standard for regulatory assessment purposes. The intercomparison measurements are an important part of the Quality Assurance work. In what is known as the sup O utside workers ' directive it is stated that the internal dose measurements shall be included in the European Unions supervision system for radiation protection. The emergency preparedness regarding internal contamination was much improved by the training with and calibration of handheld instruments from participants' laboratories. More improvement will be gained with the handbook giving practical instructions on what to do in case of e...

  12. Dose Reduction Techniques

    International Nuclear Information System (INIS)

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program

  13. Radioactive cloud dose calculations

    International Nuclear Information System (INIS)

    Radiological dosage principles, as well as methods for calculating external and internal dose rates, following dispersion and deposition of radioactive materials in the atmosphere are described. Emphasis has been placed on analytical solutions that are appropriate for hand calculations. In addition, the methods for calculating dose rates from ingestion are discussed. A brief description of several computer programs are included for information on radionuclides. There has been no attempt to be comprehensive, and only a sampling of programs has been selected to illustrate the variety available

  14. Repeat Whole Brain Radiation Therapy with a Simultaneous Infield Boost: A Novel Technique for Reirradiation

    Directory of Open Access Journals (Sweden)

    William A. Hall

    2014-01-01

    Full Text Available The treatment of patients who experience intracranial progression after whole brain radiation therapy (WBRT is a clinical challenge. Novel radiation therapy delivery technologies are being applied with the objective of improving tumor and symptom control in these patients. The purpose of this study is to describe the clinical outcomes of the application of a novel technology to deliver repeat WBRT with volume modulated arc therapy (VMAT and a simultaneous infield boost (WB-SIB to gross disease. A total of 16 patients were initially treated with WBRT between 2000 and 2008 and then experienced intracranial progression, were treated using repeat WB-SIB, and were analyzed. The median dose for the first course of WBRT was 35 Gy (range: 30–50.4 Gy. Median time between the initial course of WBRT and repeat WB-SIB was 11.3 months. The median dose at reirradiation was 20 Gy to the whole brain with a median boost dose of 30 Gy to gross disease. A total of 2 patients demonstrated radiographic disease progression after treatment. The median overall survival (OS time from initial diagnosis of brain metastases was 18.9 months (range: 7.1–66.6 (95% CI: 0.8–36.9. The median OS time after initiation of reirradiation for all patients was 2.7 months (range: 0.46–14.46 (95% CI: 1.3–8.7. Only 3 patients experienced CTCAE grade 3 fatigue. No other patients experienced any ≥ CTCAE grade 3 toxicity. This analysis reports the result of a novel RT delivery technique for the treatment of patients with recurrent brain metastases. Side effects were manageable and comparable to other conventional repeat WBRT series. Repeat WB-SIB using the VMAT RT delivery technology is feasible and appears to have acceptable short-term acute toxicity. These results may provide a foundation for further exploration of the WB-SIB technique for repeat WBRT in future prospective clinical trials.

  15. Automated Planning in Repeated Adversarial Games

    CERN Document Server

    de Cote, Enrique Munoz; Sykulski, Adam M; Jennings, Nicholas R

    2012-01-01

    Game theory's prescriptive power typically relies on full rationality and/or self-play interactions. In contrast, this work sets aside these fundamental premises and focuses instead on heterogeneous autonomous interactions between two or more agents. Specifically, we introduce a new and concise representation for repeated adversarial (constant-sum) games that highlight the necessary features that enable an automated planing agent to reason about how to score above the game's Nash equilibrium, when facing heterogeneous adversaries. To this end, we present TeamUP, a model-based RL algorithm designed for learning and planning such an abstraction. In essence, it is somewhat similar to R-max with a cleverly engineered reward shaping that treats exploration as an adversarial optimization problem. In practice, it attempts to find an ally with which to tacitly collude (in more than two-player games) and then collaborates on a joint plan of actions that can consistently score a high utility in adversarial repeated gam...

  16. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  17. Extending Teach and Repeat to Pivoting Wheelchairs

    Directory of Open Access Journals (Sweden)

    Guillermo Del Castillo

    2003-02-01

    Full Text Available The paper extends the teach-and-repeat paradigm that has been successful for the control of holonomic robots to nonholonomic wheelchairs which may undergo pivoting action over the course of their taught movement. Due to the nonholonomic nature of the vehicle kinematics, estimation is required -- in the example given herein, based upon video detection of wall-mounted cues -- both in the teaching and the tracking events. In order to accommodate motion that approaches pivoting action as well as motion that approaches straight-line action, the estimation equations of the Extended Kalman Filter and the control equations are formulated using two different definitions of a nontemporal independent variable. The paper motivates the need for pivoting action in real-life settings by reporting extensively on the abilities and limitations of estimation-based teach-and-repeat action where pivoting and near-pivoting action is disallowed. Following formulation of the equations in the near-pivot mode, the paper reports upon experiments where taught trajectories which entail a seamless mix of near-straight and near-pivot action are tracked.

  18. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty;

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  19. A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma

    International Nuclear Information System (INIS)

    Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed ± enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade ≥3 or any hematological toxicity rated as ≥4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

  20. Comparative response of dogs and monkeys to sublethal acute and continuous low dose-rate gamma-ray exposure

    International Nuclear Information System (INIS)

    Monkeys (Macaca mulatta) and dogs (beagle) were given thirteen 100-rad gamma-ray doses at 28-day intervals. The comparative response (injury and recovery) of the hematopoietic system of the two species was observed at 7-day intervals during the exposure regime. At 84 days after the thirteenth gamma-ray dose, the 1300-rad conditioned and control dogs and monkeys were challenged continuously with 35 R/day until death to determine the amount of radiation-induced injury remaining in conditioned animals as a reduction in mean survival time. Dogs (50 percent) and monkeys (8 percent) died from injury incurred during the conditioning exposures. Thus, the comparative response of dogs and monkeys to dose protraction by acute dose fractionation was similar to what might be expected from a single acute dose. Mean survival times for nonconditioned dogs and monkeys during continuous exposure at 35 R/day were the same (approximately 1400 h). Thus, hematopoietic response of the two species by this method of dose protraction was not significantly different. Mean survival times of conditioned dogs and monkeys during the continuous 35 R/day gamma-ray challenge exposure were greater than for their control counterparts. Thus, the long-term radiation-induced injury was not measurable by this method. Conditioning doses of more than four times the acute LD50-30 in dogs and approximately two times that of monkeys served only to increase both mean survival time and variance in a gamma-ray stress environment with a dose rate of 35 R/day

  1. Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity

    OpenAIRE

    Gemayel, Rita; Chavali, Sreenivas; Pougach, Ksenia; Legendre, Matthieu; Zhu, Bo; Boeynaems, Steven; van der Zande, Elisa; Gevaert, Kris; Rousseau, Frederic; Schymkowitz, Joost; Babu, M Madan; Verstrepen, Kevin J.

    2015-01-01

    Summary Excessive expansions of glutamine (Q)-rich repeats in various human proteins are known to result in severe neurodegenerative disorders such as Huntington’s disease and several ataxias. However, the physiological role of these repeats and the consequences of more moderate repeat variation remain unknown. Here, we demonstrate that Q-rich domains are highly enriched in eukaryotic transcription factors where they act as functional modulators. Incremental changes in the number of repeats i...

  2. Quantum repeaters free of polarization disturbance and phase noise

    OpenAIRE

    Yin, Zhen-Qiang; Zhao, Yi-bo; Yong YANG; Han, Zheng-Fu; Guo, Guang-Can

    2009-01-01

    Original quantum repeater protocols based on single-photon interference suffer from phase noise of the channel, which makes the long-distance quantum communication infeasible. Fortunately, two-photon interference type quantum repeaters can be immune to phase noise of the channel. However, this type quantum repeaters may still suffer from polarization disturbance of the channel. Here we propose a quantum repeaters protocol which is free of polarization disturbance of the channel based on the i...

  3. Effects of dose, dose-rate and fraction on radiation-induced breast and lung cancers

    International Nuclear Information System (INIS)

    Recent results from a large Canadian epidemiologic cohort study of low-LET radiation and cancer will be described. This is a study of 64,172 tuberculosis patients first treated in Canada between 1930 and 1952, of whom many received substantial doses to breast and lung tissue from repeated chest fluoroscopies. The mortality of the cohort between 1950 and 1987 has been determined by computerized record linkage to the National Mortality Data Base. There is a strong positive association between radiation and breast cancer risk among the females in the cohort, but in contrast very little evidence of any increased risk in lung cancer. The results of this and other studies suggest that the effect of dose-rate and/or fractionation on cancer risk may will differ depending upon the particular cancer being considered. (author)

  4. Dose Reduction Techniques

    CERN Document Server

    Waggoner, L O

    2000-01-01

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the sm...

  5. Dose reduction in molecular breast imaging

    Science.gov (United States)

    Wagenaar, Douglas J.; Chowdhury, Samir; Hugg, James W.; Moats, Rex A.; Patt, Bradley E.

    2011-10-01

    Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of 99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

  6. Design of radiation dose tumor response assays

    International Nuclear Information System (INIS)

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

  7. Ultraviolet radiation therapy and UVR dose models

    Energy Technology Data Exchange (ETDEWEB)

    Grimes, David Robert, E-mail: davidrobert.grimes@oncology.ox.ac.uk [School of Physical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland and Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratory, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom)

    2015-01-15

    Ultraviolet radiation (UVR) has been an effective treatment for a number of chronic skin disorders, and its ability to alleviate these conditions has been well documented. Although nonionizing, exposure to ultraviolet (UV) radiation is still damaging to deoxyribonucleic acid integrity, and has a number of unpleasant side effects ranging from erythema (sunburn) to carcinogenesis. As the conditions treated with this therapy tend to be chronic, exposures are repeated and can be high, increasing the lifetime probability of an adverse event or mutagenic effect. Despite the potential detrimental effects, quantitative ultraviolet dosimetry for phototherapy is an underdeveloped area and better dosimetry would allow clinicians to maximize biological effect whilst minimizing the repercussions of overexposure. This review gives a history and insight into the current state of UVR phototherapy, including an overview of biological effects of UVR, a discussion of UVR production, illness treated by this modality, cabin design and the clinical implementation of phototherapy, as well as clinical dose estimation techniques. Several dose models for ultraviolet phototherapy are also examined, and the need for an accurate computational dose estimation method in ultraviolet phototherapy is discussed.

  8. Erroneous Memories Arising from Repeated Attempts to Remember

    Science.gov (United States)

    Henkel, Linda A.

    2004-01-01

    The impact of repeated and prolonged attempts at remembering on false memory rates was assessed in three experiments. Participants saw and imagined pictures and then made repeated recall attempts before taking a source memory test. Although the number of items recalled increased with repeated tests, the net gains were associated with more source…

  9. 47 CFR 90.247 - Mobile repeater stations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Mobile repeater stations. 90.247 Section 90.247... MOBILE RADIO SERVICES Non-Voice and Other Specialized Operations § 90.247 Mobile repeater stations. A... repeater to extend the communications range of hand-carried units subject to the following: (a)...

  10. Multiple-dose acetaminophen pharmacokinetics.

    Science.gov (United States)

    Sahajwalla, C G; Ayres, J W

    1991-09-01

    Four different treatments of acetaminophen (Tylenol) were administered in multiple doses to eight healthy volunteers. Each treatment (325, 650, 825, and 1000 mg) was administered five times at 6-h intervals. Saliva acetaminophen concentration versus time profiles were determined. Noncompartmental pharmacokinetic parameters were calculated and compared to determine whether acetaminophen exhibited linear or dose-dependent pharmacokinetics. For doses less than or equal to 18 mg/kg, area under the curve (AUC), half-life (t1/2), mean residence time (MRT), and ratio of AUC to dose for the first dose were compared with the last dose. No statistically significant differences were observed in dose-corrected AUC for the first or last dose among subjects or treatments. Half-lives and MRT were not significantly different among treatments for the first or the last dose. Statistically significant differences in t1/2 and MRT were noted (p less than 0.05) among subjects for the last dose. A plot of AUC versus dose for the first and the last doses exhibited a linear relationship. Dose-corrected saliva concentration versus time curves for the treatments were superimposable. Thus, acetaminophen exhibits linear pharmacokinetics for doses of 18 mg/kg or less. Plots of AUC versus dose for one subject who received doses higher than 18 mg/kg were curved, suggesting nonlinear behavior of acetaminophen in this subject. PMID:1800709

  11. Who Repeats Algebra, and How Does Initial Performance Relate to Improvement When the Course Is Repeated?

    Science.gov (United States)

    Fong, Anthony; Jaquet, Karina; Finkelstein, Neal

    2016-01-01

    The information provided in this report shows how students perform when they repeat algebra I and how the level of improvement varies depending on initial course performance and the academic measure (course grades or CST scores). This information can help inform decisions and policies regarding whether and under what circumstances students should…

  12. Repeat Testing Effects on Credentialing Exams: Are Repeaters Misinformed or Uninformed?

    Science.gov (United States)

    Feinberg, Richard A.; Raymond, Mark R.; Haist, Steven A.

    2015-01-01

    To mitigate security concerns and unfair score gains, credentialing programs routinely administer new test material to examinees retesting after an initial failing attempt. Counterintuitively, a small but growing body of recent research suggests that repeating the identical form does not create an unfair advantage. This study builds upon and…

  13. Design principles for efficient, repeated jumpgliding

    International Nuclear Information System (INIS)

    Combined jumping and gliding locomotion, or ‘jumpgliding’, can be an efficient way for small robots or animals to travel over cluttered terrain. This paper presents functional requirements and models for a simple jumpglider which formalize the benefits and limitations of using aerodynamic surfaces to augment jumping ability. Analysis of the model gives insight into design choices and control strategies for higher performance and to accommodate special conditions such as a slippery launching surface. The model informs the design of a robotic platform that can perform repeated jumps using a carbon fiber spring and a pivoting wing. Experiments with two different versions of the platform agree with predictions from the model and demonstrate a significantly greater range, and lower cost-of-transport, than a comparable ballistic jumper. (papers)

  14. Trochlear Nerve Schwannoma With Repeated Intratumoral Hemorrhage.

    Science.gov (United States)

    Liu, Pengfei; Bao, Yuhai; Zhang, Wenchuan

    2016-09-01

    Trochlear nerve schwannoma is extremely rare, with only 35 pathologically confirmed patients being reported in the literature. Here, the authors report a patient of trochlear nerve schwannoma in the prepontine cistern manifesting as facial pain and double vision and presenting the image characteristics of repeated intratumoral hemorrhage, which has never been reported in the literature. Total tumor along with a portion of the trochlear nerve was removed by using a retrosigmoid approach. Facial pain disappeared after operation, and the diplopia remained. Follow-up studies have shown no tumor recurrence for 2 years and the simultaneous alleviation of diplopia. Information regarding the clinical presentation, radiological features and surgical outcomes of trochlear nerve schwannoma are discussed and reviewed in the paper. PMID:27607129

  15. Aging and repeated thought suppression success.

    Directory of Open Access Journals (Sweden)

    Ann E Lambert

    Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

  16. Aging and repeated thought suppression success.

    Science.gov (United States)

    Lambert, Ann E; Smyth, Frederick L; Beadel, Jessica R; Teachman, Bethany A

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility. PMID:23776442

  17. Statistical Properties of repeating FRB 121102

    CERN Document Server

    Wang, F Y

    2016-01-01

    Fast radio bursts (FRBs) are millisecond-duration radio signals possibly occurring at cosmological distances. However the physical model of FRBs is mystery, many models have been proposed. Here we study the frequency distributions of peak flux, fluence, duration and waiting time for repeating FRB 121102. The cumulative distributions of peak flux, fluence and duration show power-law forms. The waiting time distribution also shows power-law distribution, and is consistent with a non-stationary Poisson process. We also use the statistical results to test the proposed models for FRBs. Comparing with the model predications, we find that the theoretical models proposed by Dai et al. (2016) and Katz (2016) are favored. These distributions are consistent with the predications from avalanche models of driven systems.

  18. Hybrid quantum repeater using bright coherent light.

    Science.gov (United States)

    van Loock, P; Ladd, T D; Sanaka, K; Yamaguchi, F; Nemoto, Kae; Munro, W J; Yamamoto, Y

    2006-06-23

    We describe a quantum repeater protocol for long-distance quantum communication. In this scheme, entanglement is created between qubits at intermediate stations of the channel by using a weak dispersive light-matter interaction and distributing the outgoing bright coherent-light pulses among the stations. Noisy entangled pairs of electronic spin are then prepared with high success probability via homodyne detection and postselection. The local gates for entanglement purification and swapping are deterministic and measurement-free, based upon the same coherent-light resources and weak interactions as for the initial entanglement distribution. Finally, the entanglement is stored in a nuclear-spin-based quantum memory. With our system, qubit-communication rates approaching 100 Hz over 1280 km with fidelities near 99% are possible for reasonable local gate errors.

  19. Toxicology study assessing efficacy and safety of repeated administration of lipid/DNA complexes to mouse lung.

    Science.gov (United States)

    Alton, E W F W; Boyd, A C; Cheng, S H; Davies, J C; Davies, L A; Dayan, A; Gill, D R; Griesenbach, U; Higgins, T; Hyde, S C; Innes, J A; McLachlan, G; Porteous, D; Pringle, I; Scheule, R K; Sumner-Jones, S

    2014-01-01

    For gene therapy to improve lung function in cystic fibrosis (CF) subjects, repeated administration of the gene transfer agent over the lifetime of patients is likely to be necessary. This requirement limits the utility of adenoviral and adeno-associated viral vectors (both previously evaluated in CF gene therapy trials) because of induced adaptive immune responses that render repeated dosing ineffective. For CF gene therapy trials, non-viral vectors are currently the only viable option. We previously showed that the cationic lipid formulation GL67A is the most efficient of several non-viral vectors analysed for airway gene transfer. Here, we assessed the efficacy and safety of administering 12 inhaled doses of GL67A complexed with pGM169, a CpG-free plasmid encoding human CFTR complementary DNA, into mice. We show that repeated administration of pGM169/GL67A to murine lungs is feasible, safe and achieves reproducible, dose-related and persistent gene expression (>140 days after each dose) using an aerosol generated by a clinically relevant nebuliser. This study supports progression into the first non-viral multidose lung trial in CF patients. PMID:24196086

  20. Simple sequence repeats in mycobacterial genomes

    Indian Academy of Sciences (India)

    Vattipally B Sreenu; Pankaj Kumar; Javaregowda Nagaraju; Hampapathalu A Nagarajaram

    2007-01-01

    Simple sequence repeats (SSRs) or microsatellites are the repetitive nucleotide sequences of motifs of length 1–6 bp. They are scattered throughout the genomes of all the known organisms ranging from viruses to eukaryotes. Microsatellites undergo mutations in the form of insertions and deletions (INDELS) of their repeat units with some bias towards insertions that lead to microsatellite tract expansion. Although prokaryotic genomes derive some plasticity due to microsatellite mutations they have in-built mechanisms to arrest undue expansions of microsatellites and one such mechanism is constituted by post-replicative DNA repair enzymes MutL, MutH and MutS. The mycobacterial genomes lack these enzymes and as a null hypothesis one could expect these genomes to harbour many long tracts. It is therefore interesting to analyse the mycobacterial genomes for distribution and abundance of microsatellites tracts and to look for potentially polymorphic microsatellites. Available mycobacterial genomes, Mycobacterium avium, M. leprae, M. bovis and the two strains of M. tuberculosis (CDC1551 and H37Rv) were analysed for frequencies and abundance of SSRs. Our analysis revealed that the SSRs are distributed throughout the mycobacterial genomes at an average of 220–230 SSR tracts per kb. All the mycobacterial genomes contain few regions that are conspicuously denser or poorer in microsatellites compared to their expected genome averages. The genomes distinctly show scarcity of long microsatellites despite the absence of a post-replicative DNA repair system. Such severe scarcity of long microsatellites could arise as a result of strong selection pressures operating against long and unstable sequences although influence of GC-content and role of point mutations in arresting microsatellite expansions can not be ruled out. Nonetheless, the long tracts occasionally found in coding as well as non-coding regions may account for limited genome plasticity in these genomes.

  1. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten;

    2013-01-01

    on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency...

  2. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

    2010-09-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  3. Effect of repeated applications of buprofezin and acephate on soil cellulases, amylase, and invertase.

    Science.gov (United States)

    Raju, M Naga; Venkateswarlu, K

    2014-10-01

    The impact of repeated applications of buprofezin and acephate, at concentrations ranging from 0.25 to 1.0 kg ha(-1), on activities of cellulases, amylase, and invertase in unamended and nitrogen, phosphorous, and potassium (NPK) fertilizer-amended soil planted with cotton was studied. The nontarget effect of selected insecticides, when applied once, twice, or thrice on soil enzyme activities, was dose-dependent; the activities decreased with increasing concentrations of insecticides. However, there was a rapid decline in activities of enzymes after three repeated applications of insecticides in unamended or NPK-amended soil. Our data clearly suggest that insecticides must be applied judiciously in pest management in order to protect the enzymes largely implicated in soil fertility. PMID:24869954

  4. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

    Science.gov (United States)

    Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C

    2009-10-01

    Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

  5. Calcium kinetics with microgram stable isotope doses and saliva sampling

    Science.gov (United States)

    Smith, S. M.; Wastney, M. E.; Nyquist, L. E.; Shih, C. Y.; Wiesmann, H.; Nillen, J. L.; Lane, H. W.

    1996-01-01

    Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.

  6. Role of DNA Polymerases in Repeat-Mediated Genome Instability

    Directory of Open Access Journals (Sweden)

    Kartik A. Shah

    2012-11-01

    Full Text Available Expansions of simple DNA repeats cause numerous hereditary diseases in humans. We analyzed the role of DNA polymerases in the instability of Friedreich’s ataxia (GAAn repeats in a yeast experimental system. The elementary step of expansion corresponded to ∼160 bp in the wild-type strain, matching the size of Okazaki fragments in yeast. This step increased when DNA polymerase α was mutated, suggesting a link between the scale of expansions and Okazaki fragment size. Expandable repeats strongly elevated the rate of mutations at substantial distances around them, a phenomenon we call repeat-induced mutagenesis (RIM. Notably, defects in the replicative DNA polymerases δ and ∊ strongly increased rates for both repeat expansions and RIM. The increases in repeat-mediated instability observed in DNA polymerase δ mutants depended on translesion DNA polymerases. We conclude that repeat expansions and RIM are two sides of the same replicative mechanism.

  7. Effects of Proton Radiation Dose, Dose Rate and Dose Fractionation on Hematopoietic Cells in Mice

    OpenAIRE

    Ware, J.H.; Sanzari, J.; Avery, S.; Sayers, C; Krigsfeld, G.; Nuth, M.; Wan, X. S.; Rusek, A.; Kennedy, A R

    2010-01-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05–0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals...

  8. Doses from radiation exposure

    CERN Document Server

    Menzel, H G

    2012-01-01

    Practical implementation of the International Commission on Radiological Protection's (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP's 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effecti...

  9. Cholinesterase inhibition and depression of the photic after discharge of flash evoked potentials following acute or repeated exposures to a mixture of carbaryl and propoxur.

    Science.gov (United States)

    Mwanza, Jean-Claude; Lyke, Danielle F; Hertzberg, Richard C; Haber, Lynne; Kohrman-Vincent, Melissa; Li, Ruosha; Pan, Yi; Lyles, Robert H; Simmons, Jane Ellen; Macmillan, Denise K; Zehr, R Dan; Swank, Adam E; Herr, David W

    2012-06-01

    Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration of the photic after discharge (PhAD) of flash evoked potentials (FEPs). In the current studies, we compared the effects of acute or repeated exposure to a mixture of carbaryl and propoxur (1:1.45 ratio; propoxur:carbaryl) on the duration of the PhAD and brain ChE activity in Long Evans rats. Animals were exposed (po) either to a single dose (0, 3, 10, 45 or 75 mg/kg), or 14 daily dosages (0, 3, 10, 30, 45 mg/kg), of the mixture. Acute and repeated treatment with 3mg/kg (or greater) of the mixture produced dose-related inhibition of brain ChE activity. Compared to controls, the PhAD duration decreased after acute administration of 75 mg/kg or repeated treatment with 30 mg/kg of the mixture. The linear relationship between the percent of control brain ChE activity and the PhAD duration was similar for both exposure paradigms. Dose-response models for the acute and repeated exposure data did not differ for brain ChE activity or the duration of the PhAD. Repeated treatment with the mixture resulted in slightly less (13-22%) erythrocyte ChE inhibition than acute exposure. Both acute and repeated treatment resulted in dose-additive results for the PhAD duration and less than dose-additive responses (6-16%) for brain ChE activity for the middle range of dosages. Acute treatment resulted in greater than dose-additive erythrocyte ChE inhibition (15-18%) at the highest dosages. In contrast, repeated treatment resulted in less than dose-additive erythrocyte ChE inhibition (16-22%) at the middle dosages. Brain and plasma levels of propoxur and carbaryl did not differ between the acute and repeated dosing paradigms. In summary, a physiological measure of central nervous system function and brain ChE activity had similar responses after acute or repeated treatment with the carbamate mixture, and brain ChE showed only small deviations from dose-additivity. Erythrocyte ChE activity had

  10. INFLUENCE OF MORINGA OLEIFERA (DRUM-STICK FRUIT EXTRACT ON HAEMATOLOGICAL PROFILE FOLLOWING REPEATED EXPOSURE TO LOW LEVELS OF ARSENIC THROUGH FEED ON RATS

    Directory of Open Access Journals (Sweden)

    Vaibhav R. Pachade

    2012-01-01

    Full Text Available Effect of Moringa oleifera fruits hot methanolic extract (MFE, if any, in minimizing the adverse reactions of repeated exposure to arsenic trioxide (AT in feed was investigated in Wistar rats with reference to haematological profile. Three groups of rats each containing 10 (5male+5female were used. The group I served as negative control. Rats of group II were fed arsenic trioxide (AT alone @ 100 ppm in feed while those of group III simultaneously received AT (@100 ppm and MFE (50 mg/kg/day for 28 days. Blood samples were collected from retroorbital plexus for estimation of hematological parameters (haemoglobin, PCV, TEC, MCH, MCHC, MCV of different groups on 0 day, 15th day and 29th day respectively. Exposure to AT through feed in group II resulted in significant (P<0.05 decrease in haemoglobin, TEC and MCHC, accompanied by increased MCV, with no significant alteration of PCV or MCH of the rats. While rats of group III treated with AT (@100 ppm and MFE (50 mg/kg/day also resulted in same consequences as it was in group II but it was slightly less than that of group II suggesting of mild non significant protective effect.

  11. Breast dose variability in a bi-racial population undergoing screening mammography

    International Nuclear Information System (INIS)

    This study evaluated individual and population dose variability during screening mammography among 570 white and black women in South Carolina, USA. Aspects of dosimetry that were considered include compressed breast thickness (CBT), number of films per screening session, and dose in previous or subsequent sessions. Breast dose was log-normally distributed in the population, with a geometric mean of 6.6 mGy per session. Doses were significantly higher for black women, for women with high CBT or who receive more than two views per breast, and for the mediolateral oblique, compared to the craniocaudal view. No relationship was observed between age and dose. Total dose per breast varied by a factor of 20 across the study population, but the individual's dose varied little among repeat screening sessions, especially after adjusting for the number of films received per session. These results may inform assessments of the projected risks of inducing breast cancer from screening mammography. (author)

  12. Bladder dose accumulation based on a biomechanical deformable image registration algorithm in volumetric modulated arc therapy for prostate cancer

    DEFF Research Database (Denmark)

    Andersen, E S; Muren, L P; Sørensen, T S;

    2012-01-01

    Variations in bladder position, shape and volume cause uncertainties in the doses delivered to this organ during a course of radiotherapy for pelvic tumors. The purpose of this study was to evaluate the potential of dose accumulation based on repeat imaging and deformable image registration (DIR)...

  13. Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes

    DEFF Research Database (Denmark)

    Peng, Xu; Brügger, Kim; Shen, Biao;

    2003-01-01

    Short regularly spaced repeats (SRSRs) occur in multiple large clusters in archaeal chromosomes and as smaller clusters in some archaeal conjugative plasmids and bacterial chromosomes. The sequence, size, and spacing of the repeats are generally constant within a cluster but vary between clusters....... For the crenarchaeon Sulfolobus solfataricus P2, the repeats in the genome fall mainly into two closely related sequence families that are arranged in seven clusters containing a total of 441 repeats which constitute ca. 1% of the genome. The Sulfolobus conjugative plasmid pNOB8 contains a small cluster of six repeats...... that are identical in sequence to one of the repeat variants in the S. solfataricus chromosome. Repeats from the pNOB8 cluster were amplified and tested for protein binding with cell extracts from S. solfataricus. A 17.5-kDa SRSR-binding protein was purified from the cell extracts and sequenced. The protein is N...

  14. Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities

    Directory of Open Access Journals (Sweden)

    Mario Ferreira Peixoto

    2011-06-01

    Full Text Available OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009 enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day (Group 1] and 70 increased dosing [(> 800/200 mg/day (Group 2]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.

  15. Dose Uncertainties in IMPT for Oropharyngeal Cancer in the Presence of Anatomical, Range, and Setup Errors

    Energy Technology Data Exchange (ETDEWEB)

    Kraan, Aafke C., E-mail: aafke.kraan@pi.infn.it [Erasmus MC Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Water, Steven van de; Teguh, David N.; Al-Mamgani, Abrahim [Erasmus MC Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Madden, Tom; Kooy, Hanne M. [Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Heijmen, Ben J.M.; Hoogeman, Mischa S. [Erasmus MC Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2013-12-01

    Purpose: Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions. Methods and Materials: We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation. Results: For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% >95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust. Conclusions: For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive

  16. Modelling repeatedly flaring delta-sunspots

    CERN Document Server

    Chatterjee, Piyali; Carlsson, Mats

    2016-01-01

    Active regions (AR) appearing on the surface of the Sun are classified into $\\alpha$, $\\beta$, $\\gamma$, and $\\delta$ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the $\\delta$-sunspots are known to be super-active and produce the most X-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin sub-photospheric magnetic sheet breaks into multiple flux-tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic $\\delta$-sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  17. Response to the argument on the risk of cancer with chest CT screening. Is low-dose chest CT safe?

    International Nuclear Information System (INIS)

    The steady increase in the annual number of chest CT screening has become a worldwide concern because of its associated risk of lung cancer. Epidemiological studies, however, have shown that repeated exposure to low-dose radiation does not increase the risk of lung cancer. In addition, a recent randomized controlled study on chest CT screening has shown its usefulness for reducing lung cancer mortality. We reviewed the risk of lung cancer after repeated exposure to low-dose radiation, the efficacy of chest CT screening, and device technology for reducing the irradiation dose. (author)

  18. Evaluation of safety profile of black shilajit after 91 days repeated administration in rats

    Institute of Scientific and Technical Information of China (English)

    Velmurugan C; Vivek B; Wilson E; Bharathi T; Sundaram T

    2012-01-01

    Objective: To evaluate the safety of shilajit by 91 days repeated administration in different dose levels in rats. Methods: In this study the albino rats were divided into four groups. Group I received vehicle and group II, III and IV received 500, 2500 and 5000 mg/kg of shilajit, respectively. Finally animals were sacrificed and subjected to histopathology and iron was estimated by flame atomic absorption spectroscopy and graphite furnace. Results: The result showed that there were no significant changes in iron level of treated groups when compared with control except liver (5000 mg/kg) and histological slides of all organs revealed normal except negligible changes in liver and intestine with the highest dose of shilajit. The weight of all organs was normal when compared with control. Conclusions: The result suggests that black shilajit, an Ayurvedic formulation, is safe for long term use as a dietary supplement for a number of disorders like iron deficiency anaemia.

  19. Dose-to-man studies

    International Nuclear Information System (INIS)

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

  20. Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion.

    Science.gov (United States)

    Salgado, R; Pereiro, N; López-Doval, S; Lafuente, A

    2015-09-01

    Perfluorooctane sulfonate (PFOS) is a fluorinated organic compound. This chemical is neurotoxic and can alter the pituitary secretion. This is an initial study aimed at knowing the toxic effects of high doses of PFOS on prolactin secretion and the possible mechanisms involved in these alterations. For that, adult male rats were orally treated with 3.0 and 6.0 mg of PFOS/kg body weight (b.w.)/day for 28 days. At the end of the treatment, the serum levels of prolactin and estradiol as well as the concentration of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and gamma-aminobutyric acid (GABA) were quantified in the anterior and in the mediobasal hypothalamus. PFOS, at the administered doses, reduced prolactin and estradiol secretion, increased the concentration of dopamine and GABA in the anterior hypothalamus, and decreased the ratios DOPAC/dopamine and HVA/dopamine in this same hypothalamic area. The outcomes reported in this study suggest that (1) high doses of PFOS inhibit prolactin secretion in adult male rats; (2) only the periventricular-hypophysial dopaminergic (PHDA) neurons seem to be involved in this inhibitory effect but not the tuberoinfundibular dopaminergic (TIDA) and the tuberohypophysial dopaminergic (THDA) systems; (3) GABAergic cells from the paraventricular and supraoptic nuclei could be partially responsible for the PFOS action on prolactin secretion; and finally (4) estradiol might take part in the inhibition exerted by elevated concentration of PFOS on prolactin release.

  1. Survey of simple sequence repeats in woodland strawberry (Fragaria vesca).

    Science.gov (United States)

    Guan, L; Huang, J F; Feng, G Q; Wang, X W; Wang, Y; Chen, B Y; Qiao, Y S

    2013-07-30

    The use of simple sequence repeats (SSRs), or microsatellites, as genetic markers has become popular due to their abundance and variation in length among individuals. In this study, we investigated linkage groups (LGs) in the woodland strawberry (Fragaria vesca) and demonstrated variation in the abundances, densities, and relative densities of mononucleotide, dinucleotide, and trinucleotide repeats. Mononucleotide, dinucleotide, and trinucleotide repeats were more common than longer repeats in all LGs examined. Perfect SSRs were the predominant SSR type found and their abundance was extremely stable among LGs and chloroplasts. Abundances of mononucleotide, dinucleotide, and trinucleotide repeats were positively correlated with LG size, whereas those of tetranucleotide and hexanucleotide SSRs were not. Generally, in each LG, the abundance, relative abundance, relative density, and the proportion of each unique SSR all declined rapidly as the repeated unit increased. Furthermore, the lengths and frequencies of SSRs varied among different LGs.

  2. Quasimonomorphic Mononucleotide Repeats for High-Level Microsatellite Instability Analysis

    Directory of Open Access Journals (Sweden)

    Olivier Buhard

    2004-01-01

    Full Text Available Microsatellite instability (MSI analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability.

  3. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting.

    Science.gov (United States)

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F; Ignatova, Zoya

    2016-08-26

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5' end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1. PMID:27382061

  4. Feasibility of stopping paclitaxel premedication after two doses in patients not experiencing a previous infusion hypersensitivity reaction

    OpenAIRE

    Berger, Michael J.; Dunlea, Leslie J.; Rettig, Amy E.; Lustberg, Maryam B.; Phillips, Gary S.; Charles L Shapiro

    2011-01-01

    Purpose Paclitaxel-based chemotherapy continues to be an integral component in the treatment of many solid tumors. Prolonged use of paclitaxel may result in repeated doses of premedications and potential unwanted side effects. Infusion hypersensitivity reactions occurring beyond the second dose are infrequent and not well characterized. We hypothesized that patients whose paclitaxel premedications were discontinued after two doses were unlikely to experience infusion hypersensitivity reaction...

  5. Toward a theory of repeat purchase drivers for consumer services

    OpenAIRE

    Paul, M; Hennig-Thurau, T.; Gremler, D.D.; Gwinner, K. P.; Wiertz, C.

    2009-01-01

    The marketing discipline’s knowledge about the drivers of service customers’ repeat purchase behavior is highly fragmented. This research attempts to overcome that fragmented state of knowledge by making major advances toward a theory of repeat purchase drivers for consumer services. Drawing on means–end theory, the authors develop a hierarchical classification scheme that organizes repeat purchase drivers into an integrative and comprehensive framework. They then identify drivers on the basi...

  6. Assembly of Repeat Content Using Next Generation Sequencing Data

    Energy Technology Data Exchange (ETDEWEB)

    labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

    2014-03-17

    Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

  7. Triplet repeat length bias and variation in the human transcriptome

    OpenAIRE

    Molla, Michael; Delcher, Arthur; Sunyaev, Shamil; Cantor, Charles; Kasif, Simon

    2009-01-01

    Length variation in short tandem repeats (STRs) is an important family of DNA polymorphisms with numerous applications in genetics, medicine, forensics, and evolutionary analysis. Several major diseases have been associated with length variation of trinucleotide (triplet) repeats including Huntington's disease, hereditary ataxias and spinobulbar muscular atrophy. Using the reference human genome, we have catalogued all triplet repeats in genic regions. This data revealed a bias in noncoding D...

  8. Repeatability of nest morphology in African weaver birds

    OpenAIRE

    Walsh, Patrick T.; Hansell, Mike; Borello, Wendy D.; Healy, Susan D.

    2009-01-01

    It is generally assumed that birds build nests according to a genetic 'template', little influenced by learning or memory. One way to confirm the role of genetics in nest building is to assess the repeatability of nest morphology with repeated nest attempts. Solitary weaver birds, which build multiple nests in a single breeding season, are a useful group with which to do this. Here we show that repeatability of nest morphology was low, but significant, in male Southern Masked weaver birds and...

  9. Physiological Consequences of Repeated Exposures to Conditioned Fear

    OpenAIRE

    Thompson, Robert S.; Strong, Paul V; Monika Fleshner

    2012-01-01

    Activation of the stress response evokes a cascade of physiological reactions that may be detrimental when repeated or chronic, and when triggered after exposure to psychological/emotional stressors. Investigation of the physiological mechanisms responsible for the health damaging effects requires animal paradigms that repeatedly evoke a response to psychological/emotional stressors. To this end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20 days) to a context that...

  10. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Gustav J Ullenhag

    Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

  11. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate

    OpenAIRE

    Wintzell, My; Löfstedt, Lina; Johansson, Joel; Pedersen, Anne B.; Fuxe, Jonas; Shoshan, Maria

    2012-01-01

    Cisplatin is used in treatment of several types of cancer, including epithelial ovarian carcinoma (EOC). In order to mimic clinical treatment and to investigate longterm effects of cisplatin in surviving cancer cells, two EOC cell lines were repeatedly treated with low doses. In the SKOV-3 cell line originating from malignant ascites, but not in A2780 cells from a primary tumor, this led to emergence of a stable population (SKOV-3-R) which in the absence of cisplatin showed increased motility...

  12. Effect of Intraperitoneal Administered Ginseng Total Saponins on Hyperalgesia Induced by Repeated Intramuscular Injection of Acidic Saline in Rats

    OpenAIRE

    Kim, Won Joong; Kang, Hyun; Kim, Jung Eun; Choi, Geun Joo; Shin, Hwa Yong; Baek, Chong Wha; Jung, Yong Hun; Woo, Young Choel; Kim, Su Hyun; Lee, Jeong Hyuk

    2014-01-01

    The aim of this study was to assess the antinociceptive activity of ginseng total saponins (GTS) on hyperalgesia induced by repeated intramuscular injections of acidic saline in rats and to examine the mechanisms involved. Rats were injected intraperitoneally with a 0.9% saline vehicle or various doses of GTS after the development of hyperalgesia. Rats were then injected with N-methyl-D-aspartate (NMDA) or naloxone 10 min before GTS injection. The mechanical withdrawal threshold (MWT) was ass...

  13. Dose considerations in total skin electron irradiation for mycosis fungoides

    International Nuclear Information System (INIS)

    Two hundred patients with generalized cutaneous mycosis fungoides were treated with total skin electron irradiation (TSEI) in the Lahey Clinic Radiotherapy Department-MIT High Voltage Research Laboratory between 1964 and 1973. None of the patients had any clinical evidence of extracutaneous disease at presentation. The 3-year absolute survival rate was 54% (107 patients). Analysis of these 107 long-term survivors evaluated the relation between incidence of generalized cutaneous recurrence and total treatment dose given during the initial course of TSEI. Results indicated that in patients with erythroderma, the need for a second course of TSEI was inversely related to the total dose given during the first course. However, the curve seemed to flatten at about 1,500 cGy (rad). In plaque disease, the percentage of patients who received repeated courses of TSEI seemed to be relatively constant independent of total dose given during the initial course (65% to 80%). In patients with tumor lesions, the incidence of generalized cutaneous recurrence was directly proportional to total dose. The optimal dose of TSEI for patients with mycosis fungoides may vary depending on types of skin lesions. Total dose during the initial course of TSEI should be kept relatively conservative, particularly in patients with generalized plaques where relapse rate is high allowing reserve of normal tissue tolerance for further TSEI when indicated

  14. Intragenic tandem repeat variation between Legionella pneumophila strains

    Directory of Open Access Journals (Sweden)

    Jarraud Sophie

    2008-12-01

    Full Text Available Abstract Background Bacterial genomes harbour a large number of tandem repeats, yet the possible phenotypic effects of those found within the coding region of genes are only beginning to be examined. Evidence exists from other organisms that these repeats can be involved in the evolution of new genes, gene regulation, adaptation, resistance to environmental stresses, and avoidance of the immune system. Results In this study, we have investigated the presence and variability in copy number of intragenic tandemly repeated sequences in the genome of Legionella pneumophila, the etiological agent of a severe pneumonia known as Legionnaires' disease. Within the genome of the Philadelphia strain, we have identified 26 intragenic tandem repeat sequences using conservative selection criteria. Of these, seven were "polymorphic" in terms of repeat copy number between a large number of L. pneumophila serogroup 1 strains. These strains were collected from a wide variety of environments and patients in several geographical regions. Within this panel of strains, all but one of these seven genes exhibited statistically different patterns in repeat copy number between samples from different origins (environmental, clinical, and hot springs. Conclusion These results support the hypothesis that intragenic tandem repeats could play a role in virulence and adaptation to different environments. While tandem repeats are an increasingly popular focus of molecular typing studies in prokaryotes, including in L. pneumophila, this study is the first examining the difference in tandem repeat distribution as a function of clinical or environmental origin.

  15. Coexistence of 3G repeaters with LTE base stations.

    Science.gov (United States)

    Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

    2013-01-01

    Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

  16. Differential modulation of cocaine's discriminative cue by repeated and variable stress exposure: relation to monoamine transporter levels.

    Science.gov (United States)

    Kohut, Stephen J; Decicco-Skinner, Kathleen L; Johari, Shirin; Hurwitz, Zachary E; Baumann, Michael H; Riley, Anthony L

    2012-08-01

    Discriminative stimulus functions of drugs of abuse play an important role in the acquisition, maintenance and reinstatement of drug-taking behavior. The present study tested whether two different schedules of stressor presentation, i.e., repeated and variable, for 10 days, can modify the discriminative stimulus effects of cocaine in male rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline. Dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporter levels in mesocorticolimbic areas were also measured using western blotting after stress exposure to determine if the relative ratio of these proteins may explain differences in behavior. Rats exposed to both repeated and variable stress displayed shifts in the cocaine dose-response curve but with different patterns of responding. In handled controls, ED(50) values for cocaine-like responding were stable after 10 days of handling compared to baseline. Repeated stress produced a transient left-ward shift in cocaine-like responding, indicating increased sensitivity to the cocaine cue. ED(50) values after variable stress did not differ from baseline, although maximal cocaine-like responding was lower at the two highest doses of cocaine tested at which variably stressed rats exhibited more saline-like responding. Alterations in DAT and NET were found in the Repeated Stress group and DAT and SERT in the Variable Stress group in select brain regions which may be responsible for differences in behavior. PMID:22516586

  17. Effects of low dose radiation on repair processes in human lymphocytes

    International Nuclear Information System (INIS)

    DNA excision repair was investigated in lymphocytes of persons occupationally exposed to low dose radiation of 222Rn. Autoradiographic studies of unscheduled DNA synthesis and measurement of 3H-thymidine incorporation by repair replication into double stranded and single-strand containing DNA fractions obtained by BND cellulose chromatography seem to indicate a stimulatory effect of repeated low dose radiation on repair enzymes. (author)

  18. Global Repeat Map Method for Higher Order Repeat Alpha Satellites in Human and Chimpanzee Genomes (Build 37.2 Assembly)

    OpenAIRE

    Glunčić, Matko; Rosandić, Marija; Jelovina, Denis; Dekanić, Krešimir; Vlahović, Ines; Paar, Vladimir

    2012-01-01

    Alpha satellites are tandemly repeated sequences found in all human centromeres. In addition to the functional and structural role within centromere they are also a suitable model for evolutionary stud-ies, because of being subject to concerted evolution. The Global Repeat Map (GRM) algorithm is a convenient computational tool to determine consensus repeat units and their exact size within a given genomic sequence, both of monomeric and higher-order (HOR) type. Using GRM, we identify in Build...

  19. Pharmacokinetics of marbofloxacin after single intravenous and repeat oral administration to cats.

    Science.gov (United States)

    Albarellos, G A; Montoya, L; Landoni, M F

    2005-09-01

    The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.

  20. Comparison of image quality in head CT studies with different dose-reduction strategies

    DEFF Research Database (Denmark)

    Johansen, Jeppe; Nielsen, Rikke; Fink-Jensen, Vibeke;

    account to a considerable radiation dose as many patients undergo repeated studies. Therefore, various dose-reduction strategies are applied such as automated tube current and voltage modulation and recently different iterative reconstruction algorithms. However, the trade-off of all dose......-reduction maneuvers is reduction of image quality due to image noise or artifacts. The aim of our study was therefore to find the best diagnostic images with lowest possible dose. We present results of dose- and image quality optimizing strategies of brain CT examinations at our institution. We compare sequential...... and helical head CT with different tube current and voltage settings including protocols with and without automated dose modulation and assess quality of noise reduction in conjunction with iterative reconstruction algorithms....

  1. Vocabulary Learning through Assisted and Unassisted Repeated Reading

    Science.gov (United States)

    Webb, Stuart; Chang, Anna C-S.

    2012-01-01

    Previous research investigating the effects of unassisted and assisted repeated reading has primarily focused on how each approach may contribute to improvement in reading comprehension and fluency. Incidental learning of the form and meaning of unknown or partially known words encountered through assisted and unassisted repeated reading has yet…

  2. Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

    Directory of Open Access Journals (Sweden)

    Shanshan Huang

    2015-10-01

    Full Text Available In polyglutamine (polyQ diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17, we found that a large polyQ (105 glutamines in the TATA-box-binding protein (TBP preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.

  3. Hybrid quantum repeater protocol with fast local processing

    DEFF Research Database (Denmark)

    Borregaard, Johannes; Brask, Jonatan Bohr; Sørensen, Anders Søndberg

    2012-01-01

    We propose a hybrid quantum repeater protocol combining the advantages of continuous and discrete variables. The repeater is based on the previous work of Brask et al. [ Phys. Rev. Lett. 105 160501 (2010)] but we present two ways of improving this protocol. In the previous protocol entangled single...

  4. Impact of Inclusion or Exclusion of Repeaters on Test Equating

    Science.gov (United States)

    Puhan, Gautam

    2011-01-01

    This study examined the effect of including or excluding repeaters on the equating process and results. New forms of two tests were equated to their respective old forms using either all examinees or only the first timer examinees in the new form sample. Results showed that for both tests used in this study, including or excluding repeaters in the…

  5. Secret key rates for an encoded quantum repeater

    Science.gov (United States)

    Bratzik, Sylvia; Kampermann, Hermann; Bruß, Dagmar

    2014-03-01

    We investigate secret key rates for the quantum repeater using encoding [L. Jiang et al., Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325] and compare them to the standard repeater scheme by Briegel, Dür, Cirac, and Zoller. The former scheme has the advantage of a minimal consumption of classical communication. We analyze the trade-off in the secret key rate between the communication time and the required resources. For this purpose we introduce an error model for the repeater using encoding which allows for input Bell states with a fidelity smaller than one, in contrast to the model given by L. Jiang et al. [Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325]. We show that one can correct additional errors in the encoded connection procedure of this repeater and develop a suitable decoding algorithm. Furthermore, we derive the rate of producing entangled pairs for the quantum repeater using encoding and give the minimal parameter values (gate quality and initial fidelity) for establishing a nonzero secret key. We find that the generic quantum repeater is optimal regarding the secret key rate per memory per second and show that the encoded quantum repeater using the simple three-qubit repetition code can even have an advantage with respect to the resources compared to other recent quantum repeater schemes with encoding.

  6. Development of Repeated Sprint Ability in Talented Youth Basketball Players

    NARCIS (Netherlands)

    te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

    2014-01-01

    te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated i

  7. Repeatable mechanochemical activation of dynamic covalent bonds in thermoplastic elastomers.

    Science.gov (United States)

    Imato, Keiichi; Kanehara, Takeshi; Nojima, Shiki; Ohishi, Tomoyuki; Higaki, Yuji; Takahara, Atsushi; Otsuka, Hideyuki

    2016-08-18

    Repeated mechanical scission and recombination of dynamic covalent bonds incorporated in segmented polyurethane elastomers are demonstrated by utilizing a diarylbibenzofuranone-based mechanophore and by the design of the segmented polymer structures. The repeated mechanochemical reactions can accompany clear colouration and simultaneous fading. PMID:27424868

  8. Turkish population data on the short tandem repeat locus TPOX

    DEFF Research Database (Denmark)

    Vural, B; Poda, M; Atlioglu, E;

    1998-01-01

    Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals.......Allele and genotype frequencies were determined for the STR (short tandem repeat) locus TPOX in a random Turkish population sample of 200 individuals....

  9. Short-sequence DNA repeats in prokaryotic genomes

    NARCIS (Netherlands)

    A.F. van Belkum (Alex); S. Scherer; L. van Alphen (Loek); H.A. Verbrugh (Henri)

    1998-01-01

    textabstractShort-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or heterogeneo

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-15

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

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

    International Nuclear Information System (INIS)

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

  12. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

    Directory of Open Access Journals (Sweden)

    Judge Bryan S

    2011-03-01

    Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

  13. Effects of 3-repeat tau on taxol mobility through microtubules

    Science.gov (United States)

    Park, Hyunjoo; Fygenson, Deborah; Kim, Mahn Won

    2005-03-01

    Both the anti-cancer drug taxol and the microtubule-associated protein tau suppress dynamics of microtubules (MT). We have observed taxol mobility with full-length 3-repeat tau, one of six tau isoforms, using fluorescence recovery after photobleaching (FRAP) on MTs and compare with earlier results on recombinant full-length adult 4-repeat tau. Taxol mobility becomes highly sensitive to taxol concentration in the presence of 3-repeat tau (up to 1:1 molar ratio) as it does in the presence of 4-repeat tau, but is 2 to 3 times faster at low taxol concentrations. Fitting to a mean-field binding reaction model [J.L. Ross et.al, PNAS 101:12910-5 (2004)] suggests that the presence of 3-repeat tau enhances taxol movement through pores in the MT walls.

  14. Toxicological Profile of Ultrapure 2,29,3,4,49,5,59- Heptachlorbiphenyl (PCB 180) in Adult Rats

    OpenAIRE

    Viluksela, Matti; Heikkinen, Päivi; van der Ven, Leo T. M.; Rendel, Filip; Roos, Robert; Esteban, Javier; Korkalainen, Merja; Lensu, Sanna; Miettinen, Hanna M.; Savolainen, Kari; Sankari, Satu; Lilienthal, Hellmuth; Adamsson, Annika; Toppari, Jorma; Herlin, Maria

    2014-01-01

    Abstract: PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 ...

  15. Consistency of Repeated Naming in Aphasia

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Galletta

    2015-09-01

    Full Text Available Background People with mild aphasia and healthy elderly often exhibit similar impairments on language tests of word retrieval. However, variable practice effects in object naming by three individuals with aphasia compared to young and elderly adults have been reported (Wingfield et al. 2006. Wingfield et al. (2006 found that naming of the same pictures of objects over five trials demonstrated decreasing response latencies over repeated trials for both older and younger adults, but not for individuals with aphasia. In fact, among their three participants with aphasia, response latencies in the consecutive trials differed considerably. The authors suggested that different underlying processes may be involved in word retrieval for people with aphasia compared to adults without brain injuries. In our study we aimed to further consider the effect of practice on both object and action naming in individuals with mild aphasia. Method One woman with anomic aphasia (age 38 years; WAB Aphasia Quotient = 88 and one healthy woman (age 25 years participated. Both were native English speakers and reported 18 years of formal education. Participants were tested individually, with a set of 27 object pictures and a set of 27 action pictures presented one at a time on a computer screen. The participants were instructed to name each picture as quickly as possible as soon as each picture appeared on the screen. There were 10 trials of each set of pictures, with different random orders for each trial. The order of presentation of the object and action picture sets alternated across participants. Naming responses were recorded to computer sound files for later measurements of response latencies. A brief tone was presented simultaneous with the picture onset, allowing later measurement of response latencies from the onset of picture presentation to the onset of the participant’s correct response. Results Our findings resembled those reported in Wingfield et al. (2006

  16. Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration

    NARCIS (Netherlands)

    M.R. Germans; P.C. de Witt Hamer; L.J. van Boven; K.A.H. Zwinderman; G.J. Bouma

    2010-01-01

    (1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of

  17. Low dose of methyltestosterone in ovariectomised rats improves baroreflex sensitivity without geno- and cytotoxicity.

    Science.gov (United States)

    Terra, Denise G; de Lima, Ewelyne M; do Nascimento, Andrews M; Brasil, Girlandia A; Filete, Placielle F; Kalil, Ieda C; Lenz, Dominik; Endringer, Denise C; Bissoli, Nazaré S; de Andrade, Tadeu U

    2016-08-01

    This study evaluated the effects of the isolated use of a low dose of methyltestosterone (MT) on cardiovascular reflexes and hormonal levels and its geno- and cytotoxic safety in ovariectomized rats. Female Wistar rats were divided into four groups (n = 6), respectively: SHAM (received vehicle methylcellulose 0.5%), SHAM + MT (received MT 0.05 mg/kg), OVX (received vehicle), and OVX + MT (received MT). Twenty-one days after ovariectomy, treatment was given orally daily for 28 days. The Bezold-Jarisch reflex (BJR) was analyzed by measuring the bradycardic and hypotensive responses elicited by phenylbiguanide (PBG) administration. The baroreflex sensitivity (BRS) was evaluated by phenylephrine and sodium nitroprussite. Myocyte hypertrophy was determined by morphometric analysis of H&E stained slides. Biochemical data were analyzed, as well as micronucleus assay. MT improved BRS and increased testosterone values, but did not change estradiol in the OVX group. MT did not promote changes in mean arterial pressure, heart rate, BJR, serum concentrations of troponin I, weight and histopathology of the heart. MT was able to restore the BRS in OVX rats. The geno- and cytotoxic safety of the MT was demonstrated by the absence of an increase in the micronucleus (PCEMN) or change in the ratio between normochromatic erythrocytes and polychromatic erythrocytes (NCE/PCE). PMID:27148800

  18. In-use stability of enrofloxacin solution for injection in multi-dose containers

    Directory of Open Access Journals (Sweden)

    Šandor Ksenija

    2012-01-01

    Full Text Available The in-use stability study in this paper was designed as far as possible to simulate the practical usage of multi-dose containers products in veterinary practice and to establish the influence of storage conditions on drug's quality. According to literature data, shelf-live of enrofloxacin solutions for injection tested in this study is 28 days after opening. In-use (open container stability testing of enrofloxacin injection solutions was studied during a period of 112 days, and the physical-chemical parameters and microbiological contamination were assessed. A spectrophotometric method was validated for the quantification of enrofloxacin. The validation method yielded good results and included the selectivity, linearity, intra-assay precision (1.26% RSD, inter-assay precision (1.52% RSD, limit of detection (0.18 μg/mL, limit of quantification (0.54 μg/mL and accuracy. The results of spectrophotometric analyses were presented as the mean drug concentration of enrofloxacin vs. time of sampling. The findings of physical, chemical and microbiological parameters were in accordance with the producers' specifications and no extreme changes during prescribed storage occurred. The study was extended from the drug's proposed shelf-life after opening for the next 84 days and in that period no significant changes were recorded.

  19. Enzymatic activity of granulations tissues under low doses of radiation. Biochemical analysis in rats

    International Nuclear Information System (INIS)

    This paper was designed to investigate in the rat subcutaneous sponge-induced granulation tissue under low doses of X-ray, the activity of alkaline phosphatase, 5'nucleotide phosphodiesterase and adenosine triphosphatase (ATPase) enzymes. One hundred and fourteen Wistar rats were divided into three groups, as follows: Group I as control, Group II that received single 7,14 R in split-dosis immediately after sponge-implantation at the third and fifth days postoperatively. Biopsies were taken after 7, 11, 14, 21 and 28 days and the activity of the three enzymes was determined. The results have shown that in Group II alkaline phosphatase had higher activity in the 14th day of tissue evolution when compared to Groups I and III . The 5'nucleotide phosphodiesterase activity in Group I was similar in all days checked, although in Group II the enzyme showed higher activity in 7th day and lower in 21st. In Group III the activity was higher after 14 and 7 days and lower after 28 and 21 days. There was no observation of changing in adenosine triphosphatase (ATPase) activity when the three groups were compared. (author)

  20. Genotoxic and carcinogenic risks associated with the dietary consumption of repeatedly heated coconut oil.

    Science.gov (United States)

    Srivastava, Smita; Singh, Madhulika; George, Jasmine; Bhui, Kulpreet; Murari Saxena, Anand; Shukla, Yogeshwer

    2010-11-01

    Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeated heating of edible oils can generate a number of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported to have carcinogenic potential. Consumption of these repeatedly heated oils can pose a serious health hazard. The objectives of the present study were to evaluate the genotoxic and carcinogenic risks associated with the consumption of repeatedly heated coconut oil (RCO), which is one of the commonly consumed cooking and frying medium. The PAH were analysed using HPLC in fresh CO, single-heated CO (SCO) and RCO. Results revealed the presence of certain PAH, known to possess carcinogenic potential, in RCO when compared with SCO. Oral intake of RCO in Wistar rats resulted in a significant induction of aberrant cells (P<0·05) and micronuclei (P<0·05) in a dose-dependent manner. Oxidative stress analysis showed a significant (P<0·05) decrease in the levels of antioxidant enzymes such as superoxide dismutase and catalase with a concurrent increase in reactive oxygen species and lipid peroxidation in the liver. In addition, RCO given alone and along with diethylnitrosamine for 12 weeks induced altered hepatic foci as noticed by alteration in positive (γ-glutamyl transpeptidase and glutathione-S-transferase) and negative (adenosine triphosphatase, alkaline phosphatase and glucose-6-phosphatase) hepatospecific biomarkers. A significant decrease in the relative and absolute hepatic weight of RCO-supplemented rats was recorded (P<0·05). In conclusion, dietary consumption of RCO can cause a genotoxic and preneoplastic change in the liver.

  1. Strategy When Faced with Failure: Persistence and Degree Attainment of Course Repeaters versus Non-Repeaters. AIR 2002 Forum Paper.

    Science.gov (United States)

    Fenton, Kathleen S.

    Graduation and persistence rates were compared for 184 students, 92 of whom had repeated multiple courses or at least 1 course 3 times. A control group of 92 nonrepeating students was drawn from the remaining 303 students of the entire 1996 cohort. There was no difference between the graduation rate of repeaters and nonrepeaters. The persistence…

  2. Fast in vivo volume dose reconstruction via reference dose perturbation

    International Nuclear Information System (INIS)

    Purpose: Accurate on-line reconstruction of in-vivo volume dose that accounts for both machine and patient discrepancy is not clinically available. We present a simple reference-dose-perturbation algorithm that reconstructs in-vivo volume dose fast and accurately. Methods: We modelled the volume dose as a function of the fluence map and density image. Machine (output variation, jaw/leaf position errors, etc.) and patient (setup error, weight loss, etc.) discrepancies between the plan and delivery were modelled as perturbation of the fluence map and density image, respectively. Delivered dose is modelled as perturbation of the reference dose due to change of the fluence map and density image. We used both simulated and clinical data to validate the algorithm. The planned dose was used as the reference. The reconstruction was perturbed from the reference and accounted for output-variations and the registered daily image. The reconstruction was compared with the ground truth via isodose lines and the Gamma Index. Results: For various plans and geometries, the volume doses were reconstructed in few seconds. The reconstruction generally matched well with the ground truth. For the 3%/3mm criteria, the Gamma pass rates were 98% for simulations and 95% for clinical data. The differences mainly appeared on the surface of the phantom/patient. Conclusions: A novel reference-dose-perturbation dose reconstruction model is presented. The model accounts for machine and patient discrepancy from planning. The algorithm is simple, fast, yet accurate, which makes online in-vivo 3D dose reconstruction clinically feasible.

  3. Organ Doses and Effective Doses in Pediatric Radiography: Patient-Dose Survey in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Kiljunen, T.; Tietaevaeinen, A.; Parviainen, T.; Viitala, A.; Kortesniemi, M. (Radiation Practices Regulation, Radiation and Nuclear Safety Authority, Helsinki (Finland))

    2009-01-15

    Background: Use of the effective dose in diagnostic radiology permits the radiation exposure of diverse diagnostic procedures to be quantified. Fundamental knowledge of patient doses enhances the implementation of the 'as low as reasonably achievable' (ALARA) principle. Purpose: To provide comparative information on pediatric examination protocols and patient doses in skull, sinus, chest, abdominal, and pelvic radiography examinations. Material and Methods: 24 Finnish hospitals were asked to register pediatric examination data, including patient information and examination parameters and specifications. The total number of examinations in the study was 1916 (1426 chest, 228 sinus, 96 abdominal, 94 skull, and 72 pelvic examinations). Entrance surface dose (ESD) and dose-area products (DAP) were calculated retrospectively or DAP meters were used. Organ doses and effective doses were determined using a Monte Carlo program (PCXMC). Results: There was considerable variation in examination protocols between different hospitals, indicating large variations in patient doses. Mean effective doses of different age groups ranged from 5 muSv to 14 muSv in skull and sinus examinations, from 25 muSv to 483 muSv in abdominal examinations, and from 6 muSv to 48 muSv in chest examinations. Conclusion: In chest and sinus examinations, the amount of data was extensive, allowing national pediatric diagnostic reference levels to be defined. Parameter selection in pediatric examination protocols should be harmonized in order to reduce patient doses and improve optimization

  4. Prenatal radiation doses from radiopharmaceuticals

    International Nuclear Information System (INIS)

    The radiopharmaceutical administration with diagnostic or therapeutic purpose during pregnancy implies a prenatal radiation dose. The dose assessment and the evaluation of the radiological risks become relevant due to the great radiosensitivity of the fetal tissues in development. This paper is a revision of the available data for estimating fetal doses in the cases of the more frequently used radiopharmaceuticals in nuclear medicine, taking into account recent investigation in placental crossover. The more frequent diagnostic and therapeutic procedures were analyzed according to the radiation doses implied. (author)

  5. Occupational dose trends in Tanzania

    International Nuclear Information System (INIS)

    This paper describes the present status of occupational radiation exposure of monitored workers in Tanzania from 1986 to 1997. The analysis of dose records observes over this period, a fluctuating trend both in the individual and collective doses. The trend is more related to the fluctuations of the number of radiation workers than to the possible radiation safety changes of the working conditions. It has been found that, the maximum annual dose for the worker in all work categories was about 18 mSv y-1. This suggests that the occupational radiation exposure in all practices satisfies the current dose limitation system. The national exposure summary shows that, the highest collective dose of 12.8 man-Sv which is 90% of the total collective dose, was due to medical applications. The applications in industry and research had a contribution of nearly 0.8 and 0.7 man-Sv respectively. From the professional point of view, the medical diagnostic radiographers received the highest collective dose of 11.2 man-Sv. Although the medical physicists recorded the minimum collective dose of nearly 0.07 man-Sv, the data shows that this profession received the highest mean dose of about 33 mSv in 12 years. Some achievements of the personnel monitoring services and suggestions for future improvement are pointed out. (author)

  6. Hanford Environmental Dose Reconstruction Project

    International Nuclear Information System (INIS)

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that populations could have received from nuclear operations at Hanford since 1944. The project is being managed and conducted by the Pacific Northwest Laboratory (PNL) under the direction of an independent Technical Steering Panel (TSP). The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from released to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demographics, agriculture, food habits; and, environmental pathways and dose estimates

  7. Management of pediatric radiation dose using Agfa computed radiography

    Energy Technology Data Exchange (ETDEWEB)

    Schaetzing, R. [Agfa Corp., Greenville, SC (United States)

    2004-10-01

    Radiation dose to patients and its management have become important considerations in modern radiographic imaging procedures, but they acquire particular significance in the imaging of children. Because of their longer life expectancy, children exposed to radiation are thought to have a significantly increased risk of radiation-related late sequelae compared to adults first exposed to radiation later in life. Therefore, current clinical thinking dictates that dose in pediatric radiography be minimized, while simultaneously ensuring sufficient diagnostic information in the image, and reducing the need for repeat exposures. Dose management obviously starts with characterization and control of the exposure technique. However, it extends farther through the imaging chain to the acquisition system, and even to the image processing techniques used to optimize acquired images for display. Further, other factors, such as quality control procedures and the ability to handle special pediatric procedures, like scoliosis exams, also come into play. The need for dose management in modern radiography systems has spawned a variety of different solutions, some of which are similar across different manufacturers, and some of which are unique. This paper covers the techniques used in Agfa Computed Radiography (CR) systems to manage dose in a pediatric environment. (orig.)

  8. Low doses of neutrons induce changes in gene expression

    International Nuclear Information System (INIS)

    Studies were designed to identify genes induced following low-dose neutron but not following γ-ray exposure in fibroblasts. Our past work had shown differences in the expression of β-protein kinase C and c-fos genes, both being induced following γ-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not γ-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to γ rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure

  9. Effects of low doses of alcohol on declarative memory in humans

    Directory of Open Access Journals (Sweden)

    José Arturo Bríñez-Horta

    2011-09-01

    Full Text Available This study assessed the effect of low doses of alcohol on two elements of explicit or declarative memory, in 16 participants, 8 women and 8 men, with The Weschler Memory Scale III Text Test. A factorial 2 * 4 counterbalanced with repeated measures design was used. There were no statistically significant differences by gender, but there were differences among doses, specially 0.150 g / Kg., which reduced episodic and semantic retrieval, between 43.9 and 62.9 % of effect strength, in intermediate term memory. These results provided evidence that alcohol in low doses has a more pronounced effect in semantic, rather than episodic memory, in the middle term

  10. Repeating and not so Repeating Large Earthquakes in the Mexican Subduction Zone

    Science.gov (United States)

    Hjorleifsdottir, V.; Singh, S.; Iglesias, A.; Perez-Campos, X.

    2013-12-01

    The rupture area and recurrence interval of large earthquakes in the mexican subduction zone are relatively small and almost the entire length of the zone has experienced a large (Mw≥7.0) earthquake in the last 100 years (Singh et al., 1981). Several segments have experienced multiple large earthquakes in this time period. However, as the rupture areas of events prior to 1973 are only approximately known, the recurrence periods are uncertain. Large earthquakes occurred in the Ometepec, Guerrero, segment in 1937, 1950, 1982 and 2012 (Singh et al., 1981). In 1982, two earthquakes (Ms 6.9 and Ms 7.0) occurred about 4 hours apart, one apparently downdip from the other (Astiz & Kanamori, 1984; Beroza et al. 1984). The 2012 earthquake on the other hand had a magnitude of Mw 7.5 (globalcmt.org), breaking approximately the same area as the 1982 doublet, but with a total scalar moment about three times larger than the 1982 doublet combined. It therefore seems that 'repeat earthquakes' in the Ometepec segment are not necessarily very similar one to another. The Central Oaxaca segment broke in large earthquakes in 1928 (Mw7.7) and 1978 (Mw7.7) . Seismograms for the two events, recorded at the Wiechert seismograph in Uppsala, show remarkable similarity, suggesting that in this area, large earthquakes can repeat. The extent to which the near-trench part of the fault plane participates in the ruptures is not well understood. In the Ometepec segment, the updip portion of the plate interface broke during the 25 Feb 1996 earthquake (Mw7.1), which was a slow earthquake and produced anomalously low PGAs (Iglesias et al., 2003). Historical records indicate that a great tsunamigenic earthquake, M~8.6, occurred in the Oaxaca region in 1787, breaking the Central Oaxaca segment together with several adjacent segments (Suarez & Albini 2009). Whether the updip portion of the fault broke in this event remains speculative, although plausible based on the large tsunami. Evidence from the

  11. Repeating earthquakes recorded by Liaoning Regional Seismograph Network

    Institute of Scientific and Technical Information of China (English)

    LI Yu-tong; WU Zhong-liang; JIANG Chang-sheng; LI Guang-ping

    2008-01-01

    In the list of 'repeating pairs' or 'doublets' of earthquakes in China identified by Schaff and Richards using tele-seismic waveform cross-correlation, there were 23 repeating pairs located in Liaoning Province. In this study the waveforms of these events were cross-correlated using records from Liaoning Regional Seismograph Network (LRSN), and the 'repeating events' in the sense of regional waveform cross-correlation were obtained. The result was compared with that of Schaff and Richards and was used for the assessment of the seismic phase picking and event location practice of LRSN. The result shows that 'repeating events' in the sense of teleseismic waveform cross-correlation and those in the sense of regional waveform cross-correlation have significant difference, al-though with some overlap. However, the overall assessment of the location accuracy and the phase pick errors of LRSN by using these two sets of 'repeating events', respectively, provides similar results, while 'repeating events' in the sense of regional waveform cross-correlation seem to be better performing in such an assessment. With the assumption that the separation between the 'repeaters' be less than 1 km, the uncertainty in routine earthquake location of LRSN is estimated to be below 5 km, with the average of 2 km. In the observational bulletins of LRSN the time error in phase picking is estimated to be within±Is for 94% Pg readings and for 88% Sg readings.

  12. Exploring the repeat protein universe through computational protein design.

    Science.gov (United States)

    Brunette, T J; Parmeggiani, Fabio; Huang, Po-Ssu; Bhabha, Gira; Ekiert, Damian C; Tsutakawa, Susan E; Hura, Greg L; Tainer, John A; Baker, David

    2015-12-24

    A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally occurring repeat proteins have been re-engineered for molecular recognition and modular scaffolding applications. Here we use computational protein design to investigate the space of folded structures that can be generated by tandem repeating a simple helix-loop-helix-loop structural motif. Eighty-three designs with sequences unrelated to known repeat proteins were experimentally characterized. Of these, 53 are monomeric and stable at 95 °C, and 43 have solution X-ray scattering spectra consistent with the design models. Crystal structures of 15 designs spanning a broad range of curvatures are in close agreement with the design models with root mean square deviations ranging from 0.7 to 2.5 Å. Our results show that existing repeat proteins occupy only a small fraction of the possible repeat protein sequence and structure space and that it is possible to design novel repeat proteins with precisely specified geometries, opening up a wide array of new possibilities for biomolecular engineering.

  13. A De Novo Genome Assembly Algorithm for Repeats and Nonrepeats

    Directory of Open Access Journals (Sweden)

    Shuaibin Lian

    2014-01-01

    Full Text Available Background. Next generation sequencing platforms can generate shorter reads, deeper coverage, and higher throughput than those of the Sanger sequencing. These short reads may be assembled de novo before some specific genome analyses. Up to now, the performances of assembling repeats of these current assemblers are very poor. Results. To improve this problem, we proposed a new genome assembly algorithm, named SWA, which has four properties: (1 assembling repeats and nonrepeats; (2 adopting a new overlapping extension strategy to extend each seed; (3 adopting sliding window to filter out the sequencing bias; and (4 proposing a compensational mechanism for low coverage datasets. SWA was evaluated and validated in both simulations and real sequencing datasets. The accuracy of assembling repeats and estimating the copy numbers is up to 99% and 100%, respectively. Finally, the extensive comparisons with other eight leading assemblers show that SWA outperformed others in terms of completeness and correctness of assembling repeats and nonrepeats. Conclusions. This paper proposed a new de novo genome assembly method for resolving complex repeats. SWA not only can detect where repeats or nonrepeats are but also can assemble them completely from NGS data, especially for assembling repeats. This is the advantage over other assemblers.

  14. Tandem-repeat protein domains across the tree of life

    Directory of Open Access Journals (Sweden)

    Kristin K. Jernigan

    2015-01-01

    Full Text Available Tandem-repeat protein domains, composed of repeated units of conserved stretches of 20–40 amino acids, are required for a wide array of biological functions. Despite their diverse and fundamental functions, there has been no comprehensive assessment of their taxonomic distribution, incidence, and associations with organismal lifestyle and phylogeny. In this study, we assess for the first time the abundance of armadillo (ARM and tetratricopeptide (TPR repeat domains across all three domains in the tree of life and compare the results to our previous analysis on ankyrin (ANK repeat domains in this journal. All eukaryotes and a majority of the bacterial and archaeal genomes analyzed have a minimum of one TPR and ARM repeat. In eukaryotes, the fraction of ARM-containing proteins is approximately double that of TPR and ANK-containing proteins, whereas bacteria and archaea are enriched in TPR-containing proteins relative to ARM- and ANK-containing proteins. We show in bacteria that phylogenetic history, rather than lifestyle or pathogenicity, is a predictor of TPR repeat domain abundance, while neither phylogenetic history nor lifestyle predicts ARM repeat domain abundance. Surprisingly, pathogenic bacteria were not enriched in TPR-containing proteins, which have been associated within virulence factors in certain species. Taken together, this comparative analysis provides a newly appreciated view of the prevalence and diversity of multiple types of tandem-repeat protein domains across the tree of life. A central finding of this analysis is that tandem repeat domain-containing proteins are prevalent not just in eukaryotes, but also in bacterial and archaeal species.

  15. Analysis of repeated outcome measures from longitudinal studies

    Institute of Scientific and Technical Information of China (English)

    Yuanjia WANG; Naihua DUAN

    2011-01-01

    @@ In many clinical studies repeated measurements of an outcome are collected over time.For example,in an 8-week study of treatment for obsessive compulsive disorder,the severity of the disorder may be measured weekly using the Yale-Brown-Obsessive-Compulsive-Disorder-Scale (YBOCS).For each study participant who completes the study,there will be nine repeated measures of YBOCS (a baseline assessment plus eight assessments during the course of treatment).Such a study in which participants are followed and measured repeatedly over time is called a longitudinal study and the resulting data are called longitudinal data.

  16. Frequency Bandwidth of Half-Wave Impedance Repeater

    Directory of Open Access Journals (Sweden)

    Marek Dvorsky

    2012-01-01

    Full Text Available This article brings in the second part general information about half-wave impedance repeater. The third part describes the basic functional principles of the half-wave impedance repeater using Smith chart. The main attention is focused in part four on the derivation of repeater frequency bandwidth depending on characteristics and load impedance of unknown feeder line. Derived dependences are based on the elementary features of the feeder lines with specific length. The described functionality is proved in part 4.3 by measurement of transformed impedance using vector several unbalanced feeder lines and network analyzer VNWA3+.

  17. Secure quantum network coding for controlled repeater networks

    Science.gov (United States)

    Shang, Tao; Li, Jiao; Liu, Jian-wei

    2016-07-01

    To realize efficient quantum communication based on quantum repeater, we propose a secure quantum network coding scheme for controlled repeater networks, which adds a controller as a trusted party and is able to control the process of EPR-pair distribution. As the key operations of quantum repeater, local operations and quantum communication are designed to adopt quantum one-time pad to enhance the function of identity authentication instead of local operations and classical communication. Scheme analysis shows that the proposed scheme can defend against active attacks for quantum communication and realize long-distance quantum communication with minimal resource consumption.

  18. Selective CT for PET/CT: dose reduction in Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Gelfand, Michael J.; Sharp, Susan E. [Cincinnati Children' s Hospital Medical Center, Section of Nuclear Medicine, Department of Radiology, Cincinnati, OH (United States); Palumbo, Joseph S. [Cincinnati Children' s Hospital Medical Center, Cancer and Blood Diseases Institute, Department of Pediatrics, Cincinnati, OH (United States)

    2014-08-23

    In Langerhans cell histiocytosis (LCH), FDG PET demonstrates active disease in bone. Other imaging modalities show the effects of bone destruction by LCH. To evaluate a selective CT method for reducing effective dose from FDG PET/CT in LCH, using whole-body modified attenuation correction CT at extremely low exposure settings, with repeat selective limited-volume CT at typical localization settings. Fifty-one PET/CT scans were performed in 23 LCH patients, median patient age 8.5 years (range: 1-25 years). Thirty-four were performed with modified attenuation correction CT settings, with bed positions (excluding head and neck) repeated at localization CT settings in regions with abnormal or difficult to interpret PET findings. Of 34 modified attenuation correction PET/CT scans, 10 required repeat localization CT of 1 to 3 bed positions (total: 17 bed positions). Lytic bone lesions were easily recognized at modified attenuation correction settings. Calculated average effective dose for the 34 whole-body CT scans at modified attenuation correction settings was 1.65 mSv. Average effective dose per patient for repeat imaging of 17 bed positions at localization settings was 1.19 mSv. Average total effective dose from CT for all 34 scans performed at the modified attenuation correction CT settings, including the 10 repeat localization CT scans, was 2.0 mSv. High-quality PET scans were consistently obtained with reduced FDG-administered activities of 3.7 MBq/kg (0.10 mCi/kg). In active LCH, abnormal FDG uptake was seen in all lytic bone lesions ≥9 mm, including cranial vault lesions. Substantial reduction in effective dose is possible using selective CT techniques for FDG PET/CT. (orig.)

  19. Selective CT for PET/CT: dose reduction in Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    In Langerhans cell histiocytosis (LCH), FDG PET demonstrates active disease in bone. Other imaging modalities show the effects of bone destruction by LCH. To evaluate a selective CT method for reducing effective dose from FDG PET/CT in LCH, using whole-body modified attenuation correction CT at extremely low exposure settings, with repeat selective limited-volume CT at typical localization settings. Fifty-one PET/CT scans were performed in 23 LCH patients, median patient age 8.5 years (range: 1-25 years). Thirty-four were performed with modified attenuation correction CT settings, with bed positions (excluding head and neck) repeated at localization CT settings in regions with abnormal or difficult to interpret PET findings. Of 34 modified attenuation correction PET/CT scans, 10 required repeat localization CT of 1 to 3 bed positions (total: 17 bed positions). Lytic bone lesions were easily recognized at modified attenuation correction settings. Calculated average effective dose for the 34 whole-body CT scans at modified attenuation correction settings was 1.65 mSv. Average effective dose per patient for repeat imaging of 17 bed positions at localization settings was 1.19 mSv. Average total effective dose from CT for all 34 scans performed at the modified attenuation correction CT settings, including the 10 repeat localization CT scans, was 2.0 mSv. High-quality PET scans were consistently obtained with reduced FDG-administered activities of 3.7 MBq/kg (0.10 mCi/kg). In active LCH, abnormal FDG uptake was seen in all lytic bone lesions ≥9 mm, including cranial vault lesions. Substantial reduction in effective dose is possible using selective CT techniques for FDG PET/CT. (orig.)

  20. Watermelon (Citrullus lanatus (Thunb. Matsum. and Nakai Juice Modulates Oxidative Damage Induced by Low Dose X-Ray in Mice

    Directory of Open Access Journals (Sweden)

    Mohd Khairul Amran Mohammad

    2014-01-01

    Full Text Available Watermelon is a natural product that contains high level of antioxidants and may prevent oxidative damage in tissues due to free radical generation following an exposure to ionizing radiation. The present study aimed to investigate the radioprotective effects of watermelon (Citrullus lanatus (Thunb. Matsum. and Nakai juice against oxidative damage induced by low dose X-ray exposure in mice. Twelve adult male ICR mice were randomly divided into two groups consisting of radiation (Rx and supplementation (Tx groups. Rx received filtered tap water, while Tx was supplemented with 50% (v/v watermelon juice for 28 days ad libitum prior to total body irradiation by 100 μGy X-ray on day 29. Brain, lung, and liver tissues were assessed for the levels of malondialdehyde (MDA, apurinic/apyrimidinic (AP sites, glutathione (GSH, and superoxide dismutase (SOD inhibition activities. Results showed significant reduction of MDA levels and AP sites formation of Tx compared to Rx (P<0.05. Mice supplemented with 50% watermelon juice restore the intracellular antioxidant activities by significantly increased SOD inhibition activities and GSH levels compared to Rx. These findings may postulate that supplementation of 50% watermelon (Citrullus lanatus (Thunb. Matsum. and Nakai juice could modulate oxidative damage induced by low dose X-ray exposure.

  1. Evolution of radon dose evaluation

    Directory of Open Access Journals (Sweden)

    Fujimoto Kenzo

    2004-01-01

    Full Text Available The historical change of radon dose evaluation is reviewed based on the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR reports. Since 1955, radon has been recognized as one of the important sources of exposure of the general public. However, it was not really understood that radon is the largest dose contributor until 1977 when a new concept of effective dose equivalent was introduced by International Commission on Radiological Protection. In 1982, the dose concept was also adapted by UNSCEAR and evaluated per caput dose from natural radiation. Many researches have been carried out since then. However, lots of questions have remained open in radon problems, such as the radiation weighting factor of 20 for alpha rays and the large discrepancy of risk estimation among dosimetric and epidemiological approaches.

  2. Tenofovir Disoproxil Fumarate Intravaginal Ring Protects High Dose Depot Medroxyprogesterone Acetate Treated Macaques from Multiple SHIV Exposures

    OpenAIRE

    Smith, James M.; Srinivasan, Priya; Teller, Ryan S.; Lo, Yungtai; Dinh, Chuong T.; Kiser, Patrick F.; Herold, Betsy C.

    2015-01-01

    Preclinical HIV prevention models use either a single high-dose viral challenge in depot medroxyprogesterone acetate (DMPA)-treated macaques or repeated viral challenges in cycling macaques. We tested the efficacy of an intravaginal tenofovir disoproxil fumarate (TDF) ring in a model combining repeated 30 mg injections of DMPA every 6 weeks with vaginal viral challenges weekly for 12 weeks. Twelve macaques were randomized to TDF or placebo rings. All placebo macaques became infected after a m...

  3. Disaggregation and valuation of collective dose and global circulation dose

    International Nuclear Information System (INIS)

    This study is an extension of earlier work (Jones et al 2004 J. Radiol. Prot. 24 13-27) using an adaptation of the PC-CREAM computer model (Mayall et al 1997 NRPB-SR296 (EUR 17791 EN) (Chilton: NRPB)) applied to future discharge scenarios for the nuclear fuel reprocessing plant at Sellafield, Cumbria, UK. This work showed that, of the total 3700 person-Sv collective dose delivered to the world population over 500 years integration from a particular scenario (SF3), 95% is at levels of individual dose below 0.015 μSv y-1. The collective dose delivered at individual dose rates below 0.015 μSv y-1 reflects the contribution from globally circulating radionuclides, namely 3H, 14C, 85Kr and 129I. The methodology used in the earlier work could not break down the dose from globally circulating radionuclides into bands of individual dose; the principal aim of this study is to achieve such a breakdown. The results confirm that the global circulation dose is received in the very lowest bands i.e. all below 0.015 μSv y-1 for atmospheric discharges, and all below 0.0015 μSv y-1 for discharges to the sea in the SF3 scenario. If account is taken of the argument that the monetary value of the detriment associated with collective dose should reduce with decreasing levels of individual dose or risk (Jackson et al 2004 J. Radiol. Prot. 24 41-59; NRPB 1993 Doc. NRPB 4 (2) 75-80) then it can be shown that the value of the detriment associated with discharges in the SF3 scenario would be substantially reduced compared with that derived from current conventional assumptions

  4. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    OpenAIRE

    Mayado Andrea; Torres Elisa; Gutierrez-Lopez Maria D; Colado Maria I; O'Shea Esther

    2011-01-01

    Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, ...

  5. Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.

    Science.gov (United States)

    Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot

    2015-04-01

    AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303

  6. Analysis of Simple Sequence Repeats in Genomes of Rhizobia

    Institute of Scientific and Technical Information of China (English)

    GAO Ya-mei; HAN Yi-qiang; TANG Hui; SUN Dong-mei; WANG Yan-jie; WANG Wei-dong

    2008-01-01

    Simple sequence repeats (SSRs) or microsatellites, as genetic markers, are ubiquitous in genomes of various organisms. The analysis of SSR in rhizobia genome provides useful information for a variety of applications in population genetics of rhizobia. We analyzed the occurrences, relative abundance, and relative density of SSRs, the most common in Bradyrhizobium japonicum, Mesorhizobium loti, and Sinorhizobium meliloti genomes se-quenced in the microorganisms tandem repeats database, and SSRs in the three species genomes were compared with each other. The result showed that there were 1 410, 859, and 638 SSRs in B. japonicum, M. loti, and 5. meliloti genomes, respectively. In the genomes of B. japonicum, M. loti, and 5. meliloti, tetranucleotide, pentanucleotide, and hexanucleotide repeats were more abundant and indicated higher mutation rates in these species. The least abundance was mononucleotide repeat. The SSRs type and distribution were similar among these species.

  7. Quantitation of Leishmania lipophosphoglycan repeat units by capillary electrophoresis.

    Science.gov (United States)

    Barron, Tamara L; Turco, Salvatore J

    2006-04-01

    The glycosylphosphatidylinositol (GPI)-anchored lipophosphoglycan (LPG) of Leishmania is the dominant cell surface glycoconjugate of these pathogenic parasites. LPG is structurally characterized by a series of phosphoglycan repeat units. Determining the number of repeat units per LPG molecule has proven difficult using current technologies, such as mass spectrometry. As an alternative method to quantitate the number of repeat units in LPG, a procedure based on capillary electrophoretic analysis of the proportion of mannose to 2,5-anhydromannose (derived from the nonacetylated glucosamine of the GPI anchor of LPG) was developed. The CE-based technique is sensitive and relatively rapid compared to GC-MS-based protocols. Its application was demonstrated in quantitating the number of LPG repeat units from several species of Leishmania as well as from two life-cycle stages of these organisms. PMID:16310310

  8. Correct use of repeated measures analysis of variance.

    Science.gov (United States)

    Park, Eunsik; Cho, Meehye; Ki, Chang-Seok

    2009-02-01

    In biomedical research, researchers frequently use statistical procedures such as the t-test, standard analysis of variance (ANOVA), or the repeated measures ANOVA to compare means between the groups of interest. There are frequently some misuses in applying these procedures since the conditions of the experiments or statistical assumptions necessary to apply these procedures are not fully taken into consideration. In this paper, we demonstrate the correct use of repeated measures ANOVA to prevent or minimize ethical or scientific problems due to its misuse. We also describe the appropriate use of multiple comparison tests for follow-up analysis in repeated measures ANOVA. Finally, we demonstrate the use of repeated measures ANOVA by using real data and the statistical software package SPSS (SPSS Inc., USA).

  9. Repeated morphine treatment influences operant and spatial learning differentially

    Institute of Scientific and Technical Information of China (English)

    Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

    2006-01-01

    Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

  10. Discriminant analysis for repeated measures data: a review

    Directory of Open Access Journals (Sweden)

    Lisa Lix

    2010-09-01

    Full Text Available Discriminant analysis (DA encompasses procedures for classifying observations into groups (i.e., predictive discriminative analysis and describing the relative importance of variables for distinguishing amongst groups (i.e., descriptive discriminative analysis. In recent years, a number of developments have occurred in DA procedures for the analysis of data from repeated measures designs. Specifically, DA procedures have been developed for repeated measures data characterized by missing observations and/or unbalanced measurement occasions, as well as high-dimensional data in which measurements are collected repeatedly on two or more variables. This paper reviews the literature on DA procedures for univariate and multivariate repeated measures data, focusing on covariance pattern and linear mixed-effects models. A numeric example illustrates their implementation using SAS software.

  11. Establishment Of Dose Correlation During Dose Mapping On Medical Devices

    International Nuclear Information System (INIS)

    This paper explains the work done during product dose mapping in order to get the correlation between doses at MINTec-Sinagama plant. Product used was medical devices in aluminium tubes packaged in cardboard kegs packaging with average weight of 12 kg per carton. 12 cartons were loaded in every one tote to give 0.2 g/ cm3 of density. Ceric cerous dosimeters were placed at specific locations as indicated in SP14: Product Dose Mapping, QMS of MINTec-Sinagama around three planes. Three processes were made at different days as a three replicates to show the reproducibility of measurements. (author)

  12. The Dynamics of Repeat Migration: A Markov Chain Analysis

    OpenAIRE

    Zimmermann, Klaus F.; Amelie F. Constant

    2003-01-01

    While the literature has established that there is substantial and highly selective return migration, the growing importance of repeat migration has been largely ignored. Using Markov chain analysis, this paper provides a modeling framework for repeated moves of migrants between the host and home countries. The Markov transition matrix between the states in two consecutive periods is parameterized and estimated using a logit specification and a large panel data with 14 waves. The analysis for...

  13. Allele-selective inhibition of trinucleotide repeat genes

    OpenAIRE

    Matsui, Masayuki; Corey, David R.

    2012-01-01

    Expanded trinucleotide repeats cause Huntington’s disease (HD) and many other neurodegenerative disorders. There are no cures for these devastating illnesses and treatments are urgently needed. Each trinucleotide repeat disorder is the result of the mutation of just one gene, and agents that block expression of the mutant gene offer a promising option for treatment. Therapies that block expression of both mutant and wild-type alleles can have adverse effects, challenging researchers to develo...

  14. Are major repeater patients addicted to suicidal behavior?

    Science.gov (United States)

    Blasco-Fontecilla, Hilario; Artieda-Urrutia, Paula; Berenguer-Elias, Nuria; Garcia-Vega, Juan Manuel; Fernandez-Rodriguez, Monica; Rodriguez-Lomas, Cesar; Gonzalez-Villalobos, Isabel; Iruela-Cuadrado, Luis; de Leon, José

    2014-01-01

    The literature provides support for the hypothesis that some major repeaters (individuals with >=5 lifetime suicide attempts) are addicted to suicidal behavior (SB). This study explores whether major repeaters are addicted to SB or not using 7 criteria: tolerance (Criterion 1), withdrawal (Criterion 2), loss of control (Criterion 3), problems in quitting/cutting down (Criterion 4), much time spent using (Criterion 5), substantial reduction in activities (Criterion 6), and adverse physiological/physical consequences (Criterion 7). Total dependence on SB was indicated by the presence of 3 or more of the 7 criteria in the last 12 months. This cross-sectional study at Puerta de Hierro University Hospital (Madrid, Spain) recruited 118 suicide attempters including 8 major repeaters (7%, 8/118), who were all females. The association between each SB addiction criterion, physiological dependence and total dependence with major repeater status was tested for significance and for effect size with odds ratios (ORs) and their 95% confidence intervals. As hypothesized, major repeaters met significantly higher frequency of criteria for total dependence on SB, OR=62.9 (6.4-615). A backward stepwise logistic regression model was used to provide an OR between major repeater status and total dependence status corrected by confounding variables. Age, panic disorder without agoraphobia, borderline personality disorder, history of psychiatric inpatient admission, and total dependence on SB were introduced as independent variables with major repeater status as the dependent variable. The model selected total dependence and age as the remaining significant variables in the last step. Accordingly, major repeaters appear to be addicted to SB. PMID:25580865

  15. Gene conversion homogenizes the CMT1A paralogous repeats

    OpenAIRE

    Hurles Matthew E

    2001-01-01

    Abstract Background Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Results Here, a statistical test to detect ge...

  16. Failure Characteristic of Laser Cladding Samples on Repeated Impact

    Institute of Scientific and Technical Information of China (English)

    SHI Shi-hong; ZHENG Qi-guang; FU Ge-yan; ZHANG Jin-ping

    2004-01-01

    Using self-made impact fatigue test instruments and related analytic devices,the mechanical components with laser cladding layer have been attempted.It is found that,on repeated impact force,several failure modes of the components include the surface cracks,surface plastic deformation,corrosive pitting and coat collapse,etc.The paper reported the test method and initial analysis conclusions about the unique failure characteristics of the mechanical components on repeated impact load.

  17. Fully integrated, fully automated generation of short tandem repeat profiles

    OpenAIRE

    Tan, Eugene; Rosemary S. Turingan; Hogan, Catherine; Vasantgadkar, Sameer; Palombo, Luke; Schumm, James W.; Richard F Selden

    2013-01-01

    Background The generation of short tandem repeat profiles, also referred to as ‘DNA typing,’ is not currently performed outside the laboratory because the process requires highly skilled technical operators and a controlled laboratory environment and infrastructure with several specialized instruments. The goal of this work was to develop a fully integrated system for the automated generation of short tandem repeat profiles from buccal swab samples, to improve forensic laboratory process flow...

  18. Memory-based quantum repeater in quantum information communication

    Institute of Scientific and Technical Information of China (English)

    Wu Xiang-Sheng

    2004-01-01

    This paper studies the quantum repeater in quantum information communication. We propose to introduce the photon buffer mechanism for storing photons, which uses fibre delay loops as photon memories and a programmable 1 × N switcher for distributing photon delay time. Meanwhile, we also consider entanglement purification and entanglement swapping restoration at an entanglement purification or entanglement swapping failure and introduce a protection link mechanism that allows the photonic quantum repeater of a broken connection to initiate a connection restoration process.

  19. Are major repeater patients addicted to suicidal behavior?

    Science.gov (United States)

    Blasco-Fontecilla, Hilario; Artieda-Urrutia, Paula; Berenguer-Elias, Nuria; Garcia-Vega, Juan Manuel; Fernandez-Rodriguez, Monica; Rodriguez-Lomas, Cesar; Gonzalez-Villalobos, Isabel; Iruela-Cuadrado, Luis; de Leon, José

    2014-01-01

    The literature provides support for the hypothesis that some major repeaters (individuals with >=5 lifetime suicide attempts) are addicted to suicidal behavior (SB). This study explores whether major repeaters are addicted to SB or not using 7 criteria: tolerance (Criterion 1), withdrawal (Criterion 2), loss of control (Criterion 3), problems in quitting/cutting down (Criterion 4), much time spent using (Criterion 5), substantial reduction in activities (Criterion 6), and adverse physiological/physical consequences (Criterion 7). Total dependence on SB was indicated by the presence of 3 or more of the 7 criteria in the last 12 months. This cross-sectional study at Puerta de Hierro University Hospital (Madrid, Spain) recruited 118 suicide attempters including 8 major repeaters (7%, 8/118), who were all females. The association between each SB addiction criterion, physiological dependence and total dependence with major repeater status was tested for significance and for effect size with odds ratios (ORs) and their 95% confidence intervals. As hypothesized, major repeaters met significantly higher frequency of criteria for total dependence on SB, OR=62.9 (6.4-615). A backward stepwise logistic regression model was used to provide an OR between major repeater status and total dependence status corrected by confounding variables. Age, panic disorder without agoraphobia, borderline personality disorder, history of psychiatric inpatient admission, and total dependence on SB were introduced as independent variables with major repeater status as the dependent variable. The model selected total dependence and age as the remaining significant variables in the last step. Accordingly, major repeaters appear to be addicted to SB.

  20. A note on renegotiation in repeated Bertrand duopolies

    DEFF Research Database (Denmark)

    Andersson, Ola; Wengström, Erik Roland

    2007-01-01

    Weak Renegotiation-Proofness (WRP) singles out marginal cost pricing as a unique pure-strategy equilibrium of the infinitely repeated Bertrand duopoly. We show that, with a discrete strategy space, WRP does not eliminate any relevant subgame perfect equilibrium outcome......Weak Renegotiation-Proofness (WRP) singles out marginal cost pricing as a unique pure-strategy equilibrium of the infinitely repeated Bertrand duopoly. We show that, with a discrete strategy space, WRP does not eliminate any relevant subgame perfect equilibrium outcome...

  1. DSR-Based Selective Repeat ARQ Protocol in MANET

    Institute of Scientific and Technical Information of China (English)

    张全新; 宋瀚涛

    2003-01-01

    The efficient route algorithms involved in mobile ad hoc network(MANET) are studied. An arrangement of a combination of the traditional dynamic source routing(DSR) protocol is put forward and the selective repeat ARQ protocol is put forward by analyzing and studying them in detail and providing the scheme. In networks, especially in wireless networks, the nodes are capable to process data much faster than transmission, the DSR-based selective repeat ARQ protocol has real meanings in MANET.

  2. Survey of extrachromosomal circular DNA derived from plant satellite repeats

    Directory of Open Access Journals (Sweden)

    Macas Jiří

    2008-08-01

    Full Text Available Abstract Background Satellite repeats represent one of the most dynamic components of higher plant genomes, undergoing rapid evolutionary changes of their nucleotide sequences and abundance in a genome. However, the exact molecular mechanisms driving these changes and their eventual regulation are mostly unknown. It has been proposed that amplification and homogenization of satellite DNA could be facilitated by extrachromosomal circular DNA (eccDNA molecules originated by recombination-based excision from satellite repeat arrays. While the models including eccDNA are attractive for their potential to explain rapid turnover of satellite DNA, the existence of satellite repeat-derived eccDNA has not yet been systematically studied in a wider range of plant genomes. Results We performed a survey of eccDNA corresponding to nine different families and three subfamilies of satellite repeats in ten species from various genera of higher plants (Arabidopsis, Oryza, Pisum, Secale, Triticum and Vicia. The repeats selected for this study differed in their monomer length, abundance, and chromosomal localization in individual species. Using two-dimensional agarose gel electrophoresis followed by Southern blotting, eccDNA molecules corresponding to all examined satellites were detected. EccDNA occurred in the form of nicked circles ranging from hundreds to over eight thousand nucleotides in size. Within this range the circular molecules occurred preferentially in discrete size intervals corresponding to multiples of monomer or higher-order repeat lengths. Conclusion This work demonstrated that satellite repeat-derived eccDNA is common in plant genomes and thus it can be seriously considered as a potential intermediate in processes driving satellite repeat evolution. The observed size distribution of circular molecules suggests that they are most likely generated by molecular mechanisms based on homologous recombination requiring long stretches of sequence

  3. Repeatability and reproducibility of decisions by latent fingerprint examiners.

    Directory of Open Access Journals (Sweden)

    Bradford T Ulery

    Full Text Available The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as "difficult" than for "easy" or "moderate" comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4; 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization. Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases.

  4. Matching Probabilities: The Behavioral Law and Economics of Repeated Behavior

    OpenAIRE

    Ehud Guttel; Alon Harel

    2004-01-01

    Individuals may repeatedly face a choice of whether to obey a legal rule. Conventional legal scholarship has long assumed that whether such a choice is made repeatedly or is a one-time event has little or no effect on individuals’ decisions. Following models of rational-choice theory, traditional legal analysis predicts that, in either case, individuals would behave in a way that maximizes their payoffs. A large body of experimental literature, however, suggests that individuals facing a recu...

  5. Repeated adaptive divergence of microhabitat specialization in avian feather lice

    OpenAIRE

    Johnson Kevin P; Shreve Scott M; Smith Vincent S

    2012-01-01

    Abstract Background Repeated adaptive radiations are evident when phenotypic divergence occurs within lineages, but this divergence into different forms is convergent when compared across lineages. Classic examples of such repeated adaptive divergence occur in island (for example, Caribbean Anolis lizards) and lake systems (for example, African cichlids). Host-parasite systems in many respects are analogous to island systems, where host species represent isolated islands for parasites whose l...

  6. Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

    International Nuclear Information System (INIS)

    Purpose: Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation. Methods and Materials: Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine. Results: At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% ± 5.3% and 4.9% ± 2.4% (± standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant. Conclusion: This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF

  7. Dosimetric systems of high dose, dose rate and dose uniformity in food and medical products

    International Nuclear Information System (INIS)

    In the Instituto Peruano de Energia Nuclear (IPEN) we use the chemical dosimetry Astm-E-1026 Fricke as a standard dosimetric system of reference and different routine dosimetric systems of high doses, according to the applied doses to obtain the desired effects in the treated products and the doses range determined for each type of dosimeter. Fricke dosimetry is a chemical dosimeter in aqueous solution indicating the absorbed dose by means an increase in absorbance at a specific wavelength. A calibrated spectrophotometer with controlled temperature is used to measure absorbance. The adsorbed dose range should cover from 20 to 400 Gy, the Fricke solution is extremely sensitive to organic impurities, to traces of metal ions, in preparing chemical products of reactive grade must be used and the water purity is very important. Using the referential standard dosimetric system Fricke, was determined to March 5, 2013, using the referential standard dosimetric system Astm-1026 Fricke, were irradiated in triplicate Fricke dosimeters, to 5 irradiation times (20; 30; 40; 50 and 60 seconds) and by linear regression, the dose rate of 5.400648 kGy /h was determined in the central point of the irradiation chamber (irradiator Gamma cell 220 Excel), applying the decay formula, was compared with the obtained results by manufacturers by means the same dosimetric system in the year of its manufacture, being this to the date 5.44691 kGy /h, with an error rate of 0.85. After considering that the dosimetric solution responds to the results, we proceeded to the irradiation of a sample of 200 g of cereal instant food, 2 dosimeters were placed at the lateral ends of the central position to maximum dose and 2 dosimeters in upper and lower ends as minimum dose, they were applied same irradiation times; for statistical analysis, the maximum dose rate was 6.1006 kGy /h and the minimum dose rate of 5.2185 kGy /h; with a dose uniformity of 1.16. In medical material of micro pulverized bone for

  8. Survival and growth of freshwater pulmonate and nonpulmonate snails in 28-day exposures to copper, ammonia, and pentachlorophenol

    Science.gov (United States)

    Besser, John M.; Dorman, Rebecca A.; Hardesty, Douglas K.; Ingersoll, Christopher G.

    2016-01-01

    We performed toxicity tests with two species of pulmonate snails (Lymnaea stagnalis and Physa gyrina) and four taxa of nonpulmonate snails in the family Hydrobiidae (Pyrgulopsis robusta,Taylorconcha serpenticola, Fluminicola sp., and Fontigens aldrichi). Snails were maintained in static-renewal or recirculating culture systems with adults removed periodically to isolate cohorts of offspring for toxicity testing. This method successfully produced offspring for both species of pulmonate snails and for two hydrobiid species, P. robusta and Fluminicola sp. Toxicity tests were performed for 28 days with copper, ammonia, and pentachlorophenol in hard reconstituted water with endpoints of survival and growth. Tests were started with 1-week-old L. stagnalis, 2-week-old P. gyrina, 5- to 13-week-old P. robusta and Fluminicola sp., and older juveniles and adults of several hydrobiid species. For all three chemicals, chronic toxicity values for pulmonate snails were consistently greater than those for hydrobiid snails, and hydrobiids were among the most sensitive taxa in species sensitivity distributions for all three chemicals. These results suggest that the toxicant sensitivity of nonpulmonate snails in the family Hydrobiidae would not be adequately represented by results of toxicity testing with pulmonate snails.

  9. Subacute (28-day) toxicity of furfural in Fischer 344 rats: A comparison of the oral and inhalation route

    NARCIS (Netherlands)

    Arts, J.H.E.; Muijser, H.; Appel, M.J.; Kuper, C.F.; Bessems, J.G.M.; Woutersen, R.A.

    2004-01-01

    The subacute oral and inhalation toxicity of furfural vapour was studied in Fischer 344 rats to investigate whether route-to-route extrapolation could be employed to derive the limit value for inhalation exposure from oral toxicity data. Groups of 5 rats per sex were treated by gavage daily for 28 d

  10. 29 CFR 553.230 - Maximum hours standards for work periods of 7 to 28 days-section 7(k).

    Science.gov (United States)

    2010-07-01

    ...-section 7(k). 553.230 Section 553.230 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR... Compensation Rules § 553.230 Maximum hours standards for work periods of 7 to 28 days—section 7(k). (a) For... 28 consecutive days, no overtime compensation is required under section 7(k) until the number...

  11. Statistical analysis of the effective factors on the 28 days compressive strength and setting time of the concrete

    OpenAIRE

    Bahador Abolpour; Mohammad Mehdi Afsahi; Saeed Gharib Hosseini

    2015-01-01

    In this study, the effects of various factors (weight fraction of the SiO2, Al2O3, Fe2O3, Na2O, K2O, CaO, MgO, Cl, SO3, and the Blaine of the cement particles) on the concrete compressive strength and also initial setting time have been investigated. Compressive strength and setting time tests have been carried out based on DIN standards in this study. Interactions of these factors have been obtained by the use of analysis of variance and regression equations of these factors have been obtain...

  12. Statistical analysis of the effective factors on the 28 days compressive strength and setting time of the concrete

    Directory of Open Access Journals (Sweden)

    Bahador Abolpour

    2015-09-01

    Full Text Available In this study, the effects of various factors (weight fraction of the SiO2, Al2O3, Fe2O3, Na2O, K2O, CaO, MgO, Cl, SO3, and the Blaine of the cement particles on the concrete compressive strength and also initial setting time have been investigated. Compressive strength and setting time tests have been carried out based on DIN standards in this study. Interactions of these factors have been obtained by the use of analysis of variance and regression equations of these factors have been obtained to predict the concrete compressive strength and initial setting time. Also, simple and applicable formulas with less than 6% absolute mean error have been developed using the genetic algorithm to predict these parameters. Finally, the effect of each factor has been investigated when other factors are in their low or high level.

  13. Statistical analysis of the effective factors on the 28 days compressive strength and setting time of the concrete

    OpenAIRE

    Abolpour, Bahador; Mehdi Afsahi, Mohammad; Hosseini, Saeed Gharib

    2014-01-01

    In this study, the effects of various factors (weight fraction of the SiO2, Al2O3, Fe2O3, Na2O, K2O, CaO, MgO, Cl, SO3, and the Blaine of the cement particles) on the concrete compressive strength and also initial setting time have been investigated. Compressive strength and setting time tests have been carried out based on DIN standards in this study. Interactions of these factors have been obtained by the use of analysis of variance and regression equations of these factors have been obtain...

  14. Quantum key distribution with two-segment quantum repeaters

    Energy Technology Data Exchange (ETDEWEB)

    Kampermann, Hermann; Abruzzo, Silvestre; Bruss, Dagmar [Theoretische Physik III, Heinrich-Heine-Universitaet Duesseldorf (Germany)

    2014-07-01

    Quantum repeaters represent one possible way to achieve long-distance quantum key distribution. One way of improving the repeater rate and decreasing the memory coherence time is the usage of multiplexing. Motivated by the experimental fact that long-range connections are practically demanding, we extend the analysis of the quantum repeater multiplexing protocol to the case of short-range connections. We derive formulas for the repeater rate and we show that short-range connections lead to most of the benefits of a full-range multiplexing protocol. A less demanding QKD-protocol without quantum memories was recently introduced by Lo et al. We generalize this measurement-device-independent quantum key Distribution protocol to the scenario where the repeater Station contains also heralded quantum memories. We assume either single-photon sources or weak coherent pulse sources plus decay states. We show that it is possible to significantly outperform the original proposal, even in presence of decoherence of the quantum memory. We give formulas in terms of device imperfections i.e., the quantum bit error rate and the repeater rate.

  15. Quantum repeater based on cavity QED evolutions and coherent light

    Science.gov (United States)

    Gonţa, Denis; van Loock, Peter

    2016-05-01

    In the framework of cavity QED, we propose a quantum repeater scheme that uses coherent light and chains of atoms coupled to optical cavities. In contrast to conventional repeater schemes, in our scheme there is no need for an explicit use of two-qubit quantum logical gates by exploiting solely the cavity QED evolution. In our previous work (Gonta and van Loock in Phys Rev A 88:052308, 2013), we already proposed a quantum repeater in which the entanglement between two neighboring repeater nodes was distributed using controlled displacements of input coherent light, while the produced low-fidelity entangled pairs were purified using ancillary (four-partite) entangled states. In the present work, the entanglement distribution is realized using a sequence of controlled phase shifts and displacements of input coherent light. Compared to previous coherent-state-based distribution schemes for two-qubit entanglement, our scheme here relies only upon a simple discrimination of two coherent states with opposite signs, which can be performed in a quantum mechanically optimal fashion via a beam splitter and two on-off detectors. For the entanglement purification, we employ a method that avoids the use of extra entangled ancilla states. Our repeater scheme exhibits reasonable fidelities and repeater rates providing an attractive platform for long-distance quantum communication.

  16. Two tandemly repeated telomere-associated sequences in Nicotiana plumbaginifolia.

    Science.gov (United States)

    Chen, C M; Wang, C T; Wang, C J; Ho, C H; Kao, Y Y; Chen, C C

    1997-12-01

    Two tandemly repeated telomere-associated sequences, NP3R and NP4R, have been isolated from Nicotiana plumbaginifolia. The length of a repeating unit for NP3R and NP4R is 165 and 180 nucleotides respectively. The abundance of NP3R, NP4R and telomeric repeats is, respectively, 8.4 x 10(4), 6 x 10(3) and 1.5 x 10(6) copies per haploid genome of N. plumbaginifolia. Fluorescence in situ hybridization revealed that NP3R is located at the ends and/or in interstitial regions of all 10 chromosomes and NP4R on the terminal regions of three chromosomes in the haploid genome of N. plumbaginifolia. Sequence homology search revealed that not only are NP3R and NP4R homologous to HRS60 and GRS, respectively, two tandem repeats isolated from N. tabacum, but that NP3R and NP4R are also related to each other, suggesting that they originated from a common ancestral sequence. The role of these repeated sequences in chromosome healing is discussed based on the observation that two to three copies of a telomere-similar sequence were present in each repeating unit of NP3R and NP4R. PMID:9451957

  17. Standardization of high-dose measurement of electron and gamma ray absorbed doses and dose rates

    International Nuclear Information System (INIS)

    Intense electron beams and gamma radiation fields are used for sterilizing medical devices, treating municipal wastes, processing industrial goods, controlling parasites and pathogens, and extending the shelf-life of foods. Quality control of such radiation processes depends largely on maintaining measurement quality assurance through sound dosimetry procedures in the research leading to each process, in the commissioning of that process, and in the routine dose monitoring practices. This affords documentation as to whether satisfactory dose uniformity is maintained throughout the product and throughout the process. Therefore, dosimetry at high doses and dose rates must in many radiation processes be standardized carefully, so that 'dosimetry release' of a product is verified. This standardization is initiated through preliminary dosimetry intercomparison studies such as those sponsored recently by the IAEA. This is followed by establishing periodic exercises in traceability to national or international standards of absorbed dose and dose rate. Traceability is achieved by careful selection of dosimetry methods and proven reference dosimeters capable of giving sufficiently accurate and precise 'transfer' dose assessments: (1) they must be calibrated or have well-established radiation-yield indices; (2) their radiation response characteristics must be reproducible and cover the dose range of interest; (3) they must withstand the rigours of back-and-forth mailing between a central standardizing laboratory and radiation processing facilities, without excessive errors arising due to instabilities, dosimeter batch non-uniformities, and environmental and handling stresses. (author)

  18. [Tissue-specific Changes in the Polymorphism of Simple Repeats in DNA of the Offspring of Different Sex Born from Irradiated Male or Female Mice].

    Science.gov (United States)

    Lomaeva, M G; Fomenko, L A; Vasil'eva, G V; Bezlepkin, V G

    2016-01-01

    Evidence is presented indicating the differences in the polymorphism of microsatellite (MCS) repeats in DNA of somatic tissues in the offspring of BALB/c mice of different sex born from preconceptionally irradiated males or females. Brother-sister groups of the offspring born by non-irradiated parental pairs were compared with the offspring obtained after the irradiation of one parent in the same pairs. The number of MCS repeats in DNA of somatic tissues of the offspring from irradiated males or females was compared by a polymerase chain reaction using an arbitrary primer. It was found that changes in the polymorphism of the number of MCS repeats in the offspring from the males irradiated at a dose of 2 Gy was insignificant as compared with the offspring from control animals. In the offspring born by the females irradiated at a dose of 2 Gy (which does not impair the reproductive capacity), a statistically significant increase in the polymorphism was observed. Changes in the polymorphism were different in the offspring of different sex. A higher level of polymorphism was revealed in the female offspring born from the females of the F0 generation after their irradiation at a dose of 2 Gy. The increase in the polymorphism of the number of MCS repeats in DNA was more pronounced in postmitotic tissues compared with proliferating tissues. PMID:27534065

  19. Patient dose in neonatal units

    International Nuclear Information System (INIS)

    Lung disease represents one of the most life-threatening conditions in prematurely born children. In the evaluation of the neonatal chest, the primary and most important diagnostic study is therefore the chest radiograph. Since prematurely born children are very sensitive to radiation, those radiographs may lead to a significant radiation detriment. Hence, knowledge of the patient dose is necessary to justify the exposures. A study to assess the patient doses was started at the neonatal intensive care unit (NICU) of the Univ. Hospital in Leuven. Between September 2004 and September 2005, prematurely born babies underwent on average 10 X-ray examinations in the NICU. In this sample, the maximum was 78 X-ray examinations. For chest radiographs, the median entrance skin dose was 34 μGy and the median dose area product was 7.1 mGy.cm2. By means of conversion coefficients, the measured values were converted to organ doses. Organ doses were calculated for three different weight classes: extremely low birth weight infants (2500 g). The doses to the lungs for a single chest radiograph for infants with extremely low birth weights, low birth weights and normal birth weights were 24, 25 and 32 μGy, respectively. (authors)

  20. Radiation dose estimates for radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E. [Oak Ridge Inst. of Science and Education, TN (United States). Radiation Internal Dose Information Center

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  1. Who Repeats Algebra I, and How Does Initial Performance Relate to Improvement When the Course Is Repeated? REL 2015-059

    Science.gov (United States)

    Fong, Anthony B.; Jaquet, Karina; Finkelstein, Neal

    2014-01-01

    This REL West study explores the prevalence of students repeating Algebra I, who is most likely to repeat the course, and the level of improvement for students who repeat. Using six years of data from a cohort of 3,400 first-time seventh grade students in a California school district, authors found that 44 percent of students repeated algebra I.…

  2. Effects of low doses; Effet des faibles doses

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-07-01

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

  3. Savannah River Site dose control

    International Nuclear Information System (INIS)

    Health physicists from the Brookhaven National Laboratory (BNL) visited the Savannah River Site (SRS) as one of 12 facilities operated by the Department of Energy (DOE) contractors with annual collective dose equivalents greater than 100 person-rem (100 person-cSv). Their charter was to review, evaluate and summarize as low as reasonably achievable (ALARA) techniques, methods and practices as implemented. This presentation gives an overview of the two selected ALARA practices implemented at the SRS: Administrative Exposure Limits and Goal Setting. These dose control methods are used to assure that individual and collective occupational doses are ALARA and within regulatory limits

  4. Occupational radiation doses to personnel

    International Nuclear Information System (INIS)

    Results are presented of 2-year measurements of personnel doses performed according to the program of Personel Dosimetry Centre of Leningrad Scientific Research Institute of Radiation Hygiene. Investigations were carried out in 7 regions of the USSR. Thermoluminescent ''Harshow 2000 D'' dosemeter and lithium fluoride detector were used. Mean dose for all occupational groups (defectoscopists, personnel of radioactive waste disposal, medical radiologists) is found to be not exceeding 10% of maximum permissible dose. It is concluded that working conditions of personnel tested meet the requirements of RPG-76 and sanitary rules BSR-72/80

  5. Influence of Relative Humidity, Dose Rate and Dose Fractionation on Gamma Dose Response of Glycine Dosimetric System

    OpenAIRE

    Santosh H. Shinde; T. Mukherjee

    2011-01-01

    Glycine dosimeter based on spectrophotometric read-out method has great potential for gamma dosimetry in low dose applications of radiation processing. However, external factors such as relative humidity, dose rate, and dose fractionation, may have a profound effect on its gamma dose response Influence of these factors on the gamma dose response of glycine dosimeter was studied in the present work.

  6. Biochemical and histopathological changes in the kidney and adrenal gland of rats following repeated exposure to lambda-cyhalothrin

    Directory of Open Access Journals (Sweden)

    Hassina Khaldoun Oularbi

    2014-04-01

    Full Text Available Lambda-cyhalothrin (LCT is a type II pyrethroid insecticide widely used in pest management. This study was undertaken to evaluate the toxic effects of LCT on the kidneys and adrenal glands of rats after subacute exposure. Twenty-eight 6-week-old male albino Rattus norvegicus rats were randomly assigned to four groups. Group 1 was the control group, which received distilled water. The experimental groups 2, 3 and 4 received 20.4, 30.6 and 61.2 mg/kg body weight, respectively, of LCT, administered orally over 28 days. The effects of the insecticide on various biochemical parameters were evaluated at 14 and 28 days. Histopathological studies were carried out in the kidneys and adrenal glands at the end of the experiment. Lambda-cyhalothrin, as a pyrethroid insecticide, induced significant increases (P≤0.05 in plasma urea, creatinine, uric acid and glucose concentrations, and alanine aminotransferase and aspartate aminotransferase activities after 14 and 28 days. In the rat plasma samples after 28 days, residual concentrations of LCT 1R, cis,

  7. Dose selection for prostate cancer patients based on dose comparison and dose response studies

    International Nuclear Information System (INIS)

    Purpose: To better define the appropriate dose for individual prostate cancer patients treated with three-dimensional conformal radiation therapy (3D CRT). Methods and Materials: Six hundred eighteen patients treated with 3D CRT between 4/89 and 4/97 with a median follow-up of 53 months are the subject of this study. The bNED outcomes were assessed by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. The patients were grouped into three groups by prostate-specific antigen (PSA) level (<10 ng/ml, 10-19.9 ng/ml, and 20+ ng/ml) and further subgrouped into six subgroups by favorable (T1, 2A and Gleason score ≤6 and no perineural invasion) and unfavorable characteristics (one or more of T2B, T3, Gleason 7-10, perineural invasion). Dose comparisons for bNED studies were made for each of the six subgroups by dividing patients at 76 Gy for all subgroups except the favorable <10 ng/ml subgroup, which was divided at 72.5 Gy. Five-year bNED rates were compared for the median dose of each dose comparison subgroup. Dose response functions were plotted based on 5-year bNED rates for the six patient groupings, with the data from each of the six subgroups divided into three dose groups. The 5-year bNED rate was also estimated using the dose response function and compares 73 Gy with 78 Gy. Results: Dose comparisons show a significant difference in 5-year bNED rates for three of the six subgroups but not for the favorable <10 ng/ml, the favorable 10-19.9 ng/ml, or the unfavorable ≥20 ng/ml subgroups. The significant differences ranged from 22% to 40% improvement in 5-year bNED with higher dose. Dose response functions show significant differences in 5-year bNED rates comparing 73 Gy and 78 Gy for four of the six subgroups. Again, no difference was observed for the favorable <10 ng/ml group or the unfavorable ≥20 ng/ml group. The significant differences observed in 5-year bNED ranged from 15% to 43%. Conclusions: Dose response varies by patient

  8. Influence of variations in dose and dose rates on biological effects of inhaled beta-emitting radionuclides

    International Nuclear Information System (INIS)

    The biological effects of inhaled β-emitting radionuclides, 90Y, 91Y, 144Ce and 90Sr, are being investigated in beagle dogs that received single acute exposures at 12 to 14 months of age. The aerosols studied have included 91YC13,144CeC13, 90SrC12, and 90Y, 91Y, 144Ce or 90Sr in aluminosilicate particles. Thus, 91YCl3, 144CeCl3 and the aluminosilicate containing radionuclide particles all resulted in significant exposures to lung; 91YC13, 144CeC13 an 90SrC12 resulted in significant exposures to bone; 91YC13 and 144 CeC13 resulted in significant exposures to liver. The higher initial doserate exposures have been more effective than low dose-rate exposures on a per-rad basis in producing early effects. To date (144CeO2, it was observed that, on a μCi initial lung burden per kilogram body weight basis, mice did not develop pulmonary tumours whereas beagle dogs did. To fid out the reason for this observation mice have been repeatedly exposed by inhalation to 144CeO2 to maintain lung burdens of 144Ce that resulted in radiation dose rates similar to that observed in beagle dogs. Several of the repeatedly exposed mice developed malignant pulmonary tumours. Thus, with similar dose rates and cumulative doses to the lung, mice and dogs responded in a similar manner to chronic β radiation

  9. Repeated high-intensity exercise in professional rugby union.

    Science.gov (United States)

    Austin, Damien; Gabbett, Tim; Jenkins, David

    2011-07-01

    The aim of the present study was to describe the frequency, duration, and nature of repeated high-intensity exercise in Super 14 rugby union. Time-motion analysis was used during seven competition matches over the 2008 and 2009 Super 14 seasons; five players from each of four positional groups (front row forwards, back row forwards, inside backs, and outside backs) were assessed (20 players in total). A repeated high-intensity exercise bout was considered to involve three or more sprints, and/or tackles and/or scrum/ruck/maul activities within 21 s during the same passage of play. The range of repeated high-intensity exercise bouts for each group in a match was as follows: 11-18 for front row forwards, 11-21 for back row forwards, 13-18 for inside backs, and 2-11 for outside backs. The durations of the most intense repeated high-intensity exercise bouts for each position ranged from 53 s to 165 s and the minimum recovery periods between repeated high-intensity exercise bouts ranged from 25 s for the back row forwards to 64 s for the front row forwards. The present results show that repeated high-intensity exercise bouts vary in duration and activities relative to position but all players in a game will average at least 10 changes in activity in the most demanding bouts and complete at least one tackle and two sprints. The most intense periods of activity are likely to last as long as 120 s and as little as 25 s recovery may separate consecutive repeated high-intensity exercise bouts. The present findings can be used by coaches to prepare their players for the most demanding passages of play likely to be experienced in elite rugby union. PMID:21756130

  10. SEURAT-1: Development of a Research Strategy for the Replacement of in vivo Repeated Dose Systemic Toxicity Testing

    OpenAIRE

    GOCHT Tilman; Schwarz, Michael; BERGGREN Katarina; Whelan, Maurice

    2013-01-01

    SEURAT-1 is a major European private-public research consortium that is working towards animal-free testing and the highest level of consumer protection, co-funded by Cosmetics Europe (EUR 25 million) and the European Commission under the 7th Framework Programme (EUR 25 million). A research strategy was formulated around harnessing knowledge about toxicological modes-of-action and an organisational model was developed that marries crowd-sourcing with individual excellence. The proof of the in...

  11. 40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

    Science.gov (United States)

    2010-07-01

    ... in 40 CFR Part 792—Good Laboratory Practice Standards apply to this section. The following... histopathology of the male gonads, is considered sufficient to enable detection of the majority of effects on..., specifically, effects on kidney and liver, should be performed on blood samples obtained from the selected...

  12. Repeated dose oral toxicological evaluation of concentrated barley β-glucan in CD-1 mice including a recovery phase

    NARCIS (Netherlands)

    Delaney, B.; Carlson, T.; Zheng, G.-H.; Hess, R.; Knutson, N.; Frazer, S.; Ostergren, K.; Zijverden, M. van; Knippels, L.; Jonker, D.; Penninks, A.

    2003-01-01

    The cholesterol-lowering effect observed following consumption of oats and barley is attributable to the β-glucan component of the soluble fiber fraction of these cereal grains. β-Glucan has also been reported to modulate immune activity, however, few studies have evaluated the hematological effects

  13. Health effect of low dose/low dose rate radiation

    International Nuclear Information System (INIS)

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

  14. Association of brominated proteins and changes in protein expression in the rat kidney with subcarcinogenic to carcinogenic doses of bromate

    Energy Technology Data Exchange (ETDEWEB)

    Kolisetty, Narendrababu [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States); Bull, Richard J. [MoBull Consulting, Richland, WA 99352 (United States); Muralidhara, Srinivasa; Costyn, Leah J. [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States); Delker, Don A. [School of Medicine, University of Utah, Salt Lake City, UT 84132 (United States); Guo, Zhongxian [Water Quality Office, Public Utilities Board, 608576 (Singapore); Cotruvo, Joseph A. [Joseph Cotruvo and Associates, LLC, Washington, DC 20016 (United States); Fisher, Jeffrey W. [National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Cummings, Brian S., E-mail: bsc@rx.uga.edu [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States)

    2013-10-15

    The water disinfection byproduct bromate (BrO{sub 3}{sup −}) produces cytotoxic and carcinogenic effects in rat kidneys. Our previous studies demonstrated that BrO{sub 3}{sup −} caused sex-dependent differences in renal gene and protein expression in rats and the elimination of brominated organic carbon in their urine. The present study examined changes in renal cell apoptosis and protein expression in male and female F344 rats treated with BrO{sub 3}{sup −} and associated these changes with accumulation of 3-bromotyrosine (3-BT)-modified proteins. Rats were treated with 0, 11.5, 46 and 308 mg/L BrO{sub 3}{sup −} in drinking water for 28 days and renal sections were prepared and examined for apoptosis (TUNEL-staining), 8-oxo-deoxyguanosine (8-oxoG), 3-BT, osteopontin, Kim-1, clusterin, and p-21 expression. TUNEL-staining in renal proximal tubules increased in a dose-related manner beginning at 11.5 mg BrO{sub 3}{sup −}/L in female rats and 46 mg/L in males. Increased 8-oxoG staining was observed at doses as low as 46 mg/L. Osteopontin expression also increased in a dose-related manner after treatment with 46 mg/L, in males only. In contrast, Kim-1 expression increased in a dose-related manner in both sexes, although to a greater extent in females at the highest dose. Clusterin and p21 expression also increased in a dose-related manner in both sexes. The expression of 3-BT-modified proteins only increased in male rats, following a pattern previously reported for accumulation of α-2{sub u}-globulin. Increases in apoptosis in renal proximal tubules of male and female rats at the lowest doses suggest a common mode of action for renal carcinogenesis for the two sexes that is independent of α-2{sub u}-globulin nephropathy. - Highlights: • Bromate induced nephrotoxicity in both male and female rats by similar mechanisms. • Apoptosis was seen in both male and female rats at the lowest doses tested. • Bromate-induced apoptosis correlated to 8-oxo

  15. Hanford Environmental Dose Reconstruction Project

    International Nuclear Information System (INIS)

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The TSP consists of experts in environmental pathways, epidemiology, surface-water transport, ground-water transport, statistics, demography, agriculture, meteorology, nuclear engineering, radiation dosimetry, and cultural anthropology. Included are appointed technical members representing the states of Oregon, Washington, and Idaho, a representative of Native American tribes, and an individual representing the public. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates): Source terms, environmental transport, environmental monitoring data, demography, food consumption, and agriculture, and environmental pathways and dose estimates. Progress is discussed

  16. Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice.

    Science.gov (United States)

    Schiavon, Angélica Pupin; Bonato, Jéssica Mendes; Milani, Humberto; Guimarães, Francisco Silveira; Weffort de Oliveira, Rúbia Maria

    2016-01-01

    Therapeutic effects of antidepressants and atypical antipsychotics may arise partially from their ability to stimulate neurogenesis. Cannabidiol (CBD), a phytocannabinoid present in Cannabis sativa, presents anxiolytic- and antipsychotic-like effects in preclinical and clinical settings. Anxiolytic-like effects of repeated CBD were shown in chronically stressed animals and these effects were parallel with increased hippocampal neurogenesis. However, antidepressant-like effects of repeated CBD administration in non-stressed animals have been scarcely reported. Here we investigated the behavioral consequences of single or repeated CBD administration in non-stressed animals. We also determined the effects of CBD on cell proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). Single CBD 3mg/kg administration resulted in anxiolytic-like effect in mice submitted to the elevated plus maze (EPM). In the tail suspension test (TST), single or repeated CBD administration reduced immobility time, an effect that was comparable to those of imipramine (20 mg/kg). Moreover, repeated CBD administration at a lower dose (3 mg/kg) increased cell proliferation and neurogenesis, as seen by an increased number of Ki-67-, BrdU- and doublecortin (DCX)-positive cells in both in DG and SVZ. Despite its antidepressant-like effects in the TST, repeated CBD administration at a higher dose (30 mg/kg) decreased cell proliferation and neurogenesis in the hippocampal DG and SVZ. Our findings show a dissociation between behavioral and proliferative effects of repeated CBD and suggest that the antidepressant-like effects of CBD may occur independently of adult neurogenesis in non-stressed Swiss mice. PMID:26187374

  17. Needle image plates compared to conventional CR in chest radiography: Is dose reduction possible?

    Energy Technology Data Exchange (ETDEWEB)

    Berger-Kulemann, Vanessa, E-mail: vanessa.berger-kulemann@meduniwien.ac.at [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Pötter-Lang, Sarah; Gruber, Michael [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Berger, Rudolf [Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Vonbank, Karin [Department of Internal Medicine II, Division of Pneumology, Medical University of Vienna Waehringer Guertel 18-20, 1090 Vienna (Austria); Weber, Michael [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Rabitsch, Werner [Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Uffmann, Martin [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Department of Radiology, KH Neunkirchen, Peischinger Straße 19, 2620 Neunkirchen (Austria)

    2012-12-15

    Purpose: To compare image quality of standard-dose computed radiography and dose reduced needle-technology CR for supine CXR in a clinical setting. Materials and methods: We prospectively evaluated 128 radiographs of 32 immunocompromised patients. For each patient four clinical CXR were performed within one week, two with powder image plates (PIP; Fuji ST-V) and two with needle image plates (NIP; Agfa DXS) at standard and half dose, respectively. One experienced radiologist and two residents blinded to dose level and kind of imaging system rated different anatomical structures, image noise, tubes/lines and abnormalities on a image quality scale from 1 to 10 (1 = poor, 10 = excellent). The rating scores were tested for statistical differences using analysis of variance with repeated measures. Results: A statistical difference (p < 0.05) was found for the two systems as well as for the two dose levels. Overall rating scores were 6.5 for PIP with full dose, 6.2 for PIP with half dose, 7.6 for NIP with full dose and 7.4 for NIP with half dose. There was a significant difference in favour of the NIP system at the same dose level. Also the NIP images obtained at half dose were ranked significantly better compared to the PIP images at standard dose. The differences in ranking of anatomical structures and abnormalities were more pronounced in low absorption areas (pulmonary vessels, parenchyma) than in high absorption areas (mediastinum, spine). Conclusion: For supine chest radiograms the NIP technology allows for a dose reduction of 50% while providing higher image quality.

  18. Image analysis as a non-destructive method to assess regrowth of weeds after repeated flame weeding

    DEFF Research Database (Denmark)

    Rask, Anne Merete; Kristoffersen, Palle; Andreasen, Christian

    2013-01-01

    Efficient non-chemical weed control like flame weeding often requires repeated treatments. In weed control experiments the effect of each treatment may be estimated by removing and weighing the remaining weed biomass after the treatment, but the method influences the weed plants ability to regrow......, and therefore it may influence the long-term effect of repeated treatments. Visual assessment of weed cover or image analysis do not affect the remaining parts of the weed plants after treatment, but the methods may have other disadvantages. In order to evaluate and compare three methods we measured changes......, there were significant differences in the estimated effective doses (e.g., ED50 and ED90 values) depending on assessment method and treatment frequency. One reason could be that image analysis and visual assessment did not affect the remaining weed parts after treatment and therefore gave a more realistic...

  19. Diamond gamma dose rate monitor

    International Nuclear Information System (INIS)

    CVD (chemical vapor deposition) diamond detectors for X and gamma dose rate monitoring have been fabricated and tested in the 1 mGy/h to 1 kGy/h range. They show excellent performances in terms of sensitivity and linearity. Radiation hardness measurement under 60-Co gamma rays have demonstrated long term stability for integrated doses up to 500 kGy. (authors)

  20. A contribution to the study of damage and regeneration of hemopoiesis during fractionated irradiation and repeated bone marrow transplantation

    International Nuclear Information System (INIS)

    The experiment was aimed at studying two contradictory actions: damage to hemopoietic organs during application of radiation doses per fraction and regenerative efforts of the organism support by repeated bone marrow transplantation. The mice received doses of 3 Gy or 60Co-gamma rays total body irradiation at four-day intervals up to a total dose of 18 Gy. After each dose per fraction half of the animals were injected with 106 bone marrow cells. At four-day intervals evaluations were made of the blood count, bone marrow and spleen cellularities, and spleen mass. In animals subjected only to irradiation the damage to hemopoietic organs was becoming deeper until the end of observation. In bone marrow recipients the decrease in bone marrow cellularity and the number of leukocytes stopped after day 16, and there was a steep growth of splenic cellularity and mass; the decrease in erythrocyte count stopped on day 20. Obviously a certain recovery of hemopoiesis occurred after the total dose of 12 Gy between days 12 and 16. The lodging of injected hemopoietic stem cells and their proliferation had to be preceeded by a regeneration of the hemopoietic microenvironment. (orig.)