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

Pokharel, S; Rana, S

Purpose: purpose of this study is to evaluate the effect of grid size in Eclipse AcurosXB dose calculation algorithm for SBRT lung. Methods: Five cases of SBRT lung previously treated have been chosen for present study. Four of the plans were 5 fields conventional IMRT and one was Rapid Arc plan. All five cases have been calculated with five grid sizes (1, 1.5, 2, 2.5 and 3mm) available for AXB algorithm with same plan normalization. Dosimetric indices relevant to SBRT along with MUs and time have been recorded for different grid sizes. The maximum difference was calculated as a percentagemore » of mean of all five values. All the plans were IMRT QAed with portal dosimetry. Results: The maximum difference of MUs was within 2%. The time increased was as high as 7 times from highest 3mm to lowest 1mm grid size. The largest difference of PTV minimum, maximum and mean dose were 7.7%, 1.5% and 1.6% respectively. The highest D2-Max difference was 6.1%. The highest difference in ipsilateral lung mean, V5Gy, V10Gy and V20Gy were 2.6%, 2.4%, 1.9% and 3.8% respectively. The maximum difference of heart, cord and esophagus dose were 6.5%, 7.8% and 4.02% respectively. The IMRT Gamma passing rate at 2%/2mm remains within 1.5% with at least 98% points passing with all grid sizes. Conclusion: This work indicates the lowest grid size of 1mm available in AXB is not necessarily required for accurate dose calculation. The IMRT passing rate was insignificant or not observed with the reduction of grid size less than 2mm. Although the maximum percentage difference of some of the dosimetric indices appear large, most of them are clinically insignificant in absolute dose values. So we conclude that 2mm grid size calculation is best compromise in light of dose calculation accuracy and time it takes to calculate dose.« less

Altitudinal characteristics of atmospheric deposition of aerosols in mountainous regions: Lessons from the Fukushima Daiichi Nuclear Power Station accident.

PubMed

Sanada, Yukihisa; Katata, Genki; Kaneyasu, Naoki; Nakanishi, Chika; Urabe, Yoshimi; Nishizawa, Yukiyasu

2018-03-15

To understand the formation process of radiologically contaminated areas in eastern Japan caused by the Fukushima Daiichi Nuclear Power Station (FDNPS) accident, the deposition mechanisms over complex topography are the key factors to be investigated. To characterize the atmospheric deposition processes of radionuclides over complex mountainous topography, we investigated the altitudinal distributions of the radiocesium deposited during the accident. In five selected areas, altitudinal characteristics of the air dose rates observed using airborne surveys were analyzed. To examine the deposition mechanisms, we supplementarily used vertical profiles of radiocesium deposition in each area calculated in the latest atmospheric dispersion model. In southern Iwate, the vertical profile of the observed air dose rate was uniform regardless of altitude. In western Tochigi, the areas with the highest levels of contamination were characteristically distributed in the middle of the mountains, while in southern Fukushima, the areas with the highest contamination levels were enhanced near the summits of mountains. In central Fukushima, high air dose rates were limited to the bottoms of basin-like valley. In the region northwest of FDNPS, the air dose rate was the highest at the bottom of valley topography and decreased gradually with altitude. The simulation results showed that calculated wet deposition and observed vertical profiles of total deposition were similar in areas of southern Iwate and northwest of FDNPS qualitatively, suggesting that the dominant deposition mechanism was wet deposition. In contrast, the atmospheric dispersion model failed to reproduce either the timing of precipitation events or vertical profiles of radiocesium deposition in three other areas. Although it was difficult to elucidate the deposition mechanisms in these areas due to uncertainties of the present model results, potential mechanisms such as cloud water deposition were still proposed based on circumstantial evidences of limited meteorological data during the early stage of the accident. Copyright © 2017 Elsevier B.V. All rights reserved.

Ovarian activity in obese and nonobese women treated with three transdermal contraceptive patches delivering three different doses of ethinyl estradiol and levonorgestrel.

PubMed

Foegh, Marie; Archer, David F; Stanczyk, Frank Z; Rubin, Arkady; Mishell, Daniel R

2013-02-01

The effect of obesity on ovarian follicular suppression in women using low-estrogen dose contraceptive patches has not been determined. A Phase II, parallel-group, multicenter, three-cycle study evaluated three patches containing different ethinyl estradiol (EE) and levonorgestrel (LNG) doses. Serum levels of EE, LNG, sex hormone-binding globulin and progesterone were compared in 41 obese [body mass index (BMI) ≥30] and 75 nonobese (BMI <30) women. Suppression of ovulation during the luteal phase was dose dependent, with the highest dose (AG200-15) preventing progesterone increases in all women (cycles 2-3). In the follicular phase, the lowest-dose patch had the highest rate of increased progesterone in nonobese subjects. Progesterone levels ≥3.0 ng/mL in the follicular phase were more common in obese than nonobese women. AG200-15 suppresses ovulation in obese and nonobese women. All three patches found increased progesterone in the follicular phase, albeit more in obese versus nonobese women. Copyright © 2013 Elsevier Inc. All rights reserved.

Characterization of ferrous-methylthymol blue-polyvinyl alcohol gel dosimeters using nuclear magnetic resonance and optical techniques

NASA Astrophysics Data System (ADS)

Rabaeh, Khalid A.; Eyadeh, Molham M.; Hailat, Tariq F.; Aldweri, Feras M.; Alheet, Samer M.; Eid, Rania M.

2018-07-01

A new composition of Ferrous sulphate-Metheylthymol blue (MTB)-Polyvinyl alcohol (PVA) dosimeter is introduced in this work and evaluated using nuclear magnetic resonance (NMR) and absorbance spectrophotometry techniques. The Fricke-MTB-PVA dosimeters were irradiated using a medical linear accelerator in a cubic water phantom. The dose response of the dosimeters was investigated using NMR in terms of spin-spin relaxation rate (R2), and ultraviolet and visible regions (UV-Vis) spectrophotometry in terms of absorbance. The dosimeter presents a linear dose response for doses up to 20 Gy with UV-Vis and 40 Gy with NMR method. The sample with 0.1 mM MTB, 5% PVA by weight showed highest dose sensitivity for both techniques. The Fricke-MTB-PVA dosimeter developed in this work has a significant advance over the Fricke-MTB-gelatin system: the NMR sensitivity was remarkably improved; the auto-oxidation rate was seven times lower, and no significant dose rate or photon energy effects were observed.

Glibenclamide, a Blocker of K+ATP Channels, Shows Antileishmanial Activity in Experimental Murine Cutaneous Leishmaniasis▿

PubMed Central

Serrano-Martín, Xenón; Payares, Gilberto; Mendoza-León, Alexis

2006-01-01

Glibenclamide reduced the rate of lesion growth in BALB/c mice infected with Leishmania (Leishmania) mexicana, the effect was dose dependent, and the highest dose proved more effective than glucantime. Cross-resistance to glucantime was found in animals infected with a glibenclamide-resistant line, but combined therapy reduced lesion progression even in the glibenclamide-resistant strain. PMID:17015627

Successful long-term treatment of cerebral nocardiosis with unexpectedly low doses of linezolid in an immunocompromised patient receiving complex polytherapy.

PubMed

Pea, Federico; Cojutti, Piergiorgio; Pagotto, Alberto; Cristini, Francesco; Furlanut, Mario; Viale, Pierluigi

2012-06-01

Cerebral nocardiosis is a severe infection that carries the highest mortality rate among all bacterial cerebral abscesses. We report on a case in an immunocompromised patient which was successfully treated with unexpectedly low doses of linezolid. Therapeutic drug monitoring was very helpful in highlighting issues of poor compliance and of drug-drug interactions.

Absorbed doses of lungs from radon retained in airway lumens of mice and rats.

PubMed

Sakoda, Akihiro; Ishimori, Yuu; Yamaoka, Kiyonori; Kataoka, Takahiro; Mitsunobu, Fumihiro

2013-08-01

This paper provides absorbed doses arising from radon gas in air retained in lung airway lumens. Because radon gas exposure experiments often use small animals, the calculation was performed for mice and rats. For reference, the corresponding computations were also done for humans. Assuming that radon concentration in airway lumens is the same as that in the environment, its progeny's production in and clearance from airways were simulated. Absorbed dose rates were obtained for three lung regions and the whole lung, considering that secretory and basal cells are sensitive to radiation. The results showed that absorbed dose rates for all lung regions and whole lung generally increase from mice to rats to humans. For example, the dose rates for the whole lung were 25.4 in mice, 41.7 in rats, and 59.9 pGy (Bq m⁻³)⁻¹ h⁻¹ in humans. Furthermore, these values were also compared with lung dose rates from two other types of exposures, that is, due to inhalation of radon or its progeny, which were already reported. It was confirmed that the direct inhalation of radon progeny in the natural environment, which is known as a cause of lung cancer, results in the highest dose rates for all species. Based on the present calculations, absorbed dose rates of the whole lung from radon gas were lower by a factor of about 550 (mice), 200 (rats), or 70 (humans) than those from radon progeny inhalation. The calculated dose rate values are comparatively small. Nevertheless, the present study is considered to contribute to our understanding of doses from inhalation of radon and its progeny.

Lemna minor plants chronically exposed to ionising radiation: RNA-seq analysis indicates a dose rate dependent shift from acclimation to survival strategies.

PubMed

Van Hoeck, Arne; Horemans, Nele; Nauts, Robin; Van Hees, May; Vandenhove, Hildegarde; Blust, Ronny

2017-04-01

Ecotoxicological research provides knowledge on ionising radiation-induced responses in different plant species. However, the sparse data currently available are mainly extracted from acute exposure treatments. To provide a better understanding of environmental exposure scenarios, the response to stress in plants must be followed in more natural relevant chronic conditions. We previously showed morphological and biochemical responses in Lemna minor plants continuously exposed for 7days in a dose-rate dependent manner. In this study responses on molecular (gene expression) and physiological (photosynthetic) level are evaluated in L. minor plants exposed to ionising radiation. To enable this, we examined the gene expression profiles of irradiated L. minor plants by using an RNA-seq approach. The gene expression data reveal indications that L. minor plants exposed at lower dose rates, can tolerate the exposure by triggering acclimation responses. In contrast, at the highest dose rate tested, a high number of genes related to antioxidative defense systems, DNA repair and cell cycle were differentially expressed suggesting that only high dose rates of ionising radiation drive L. minor plants into survival strategies. Notably, the photosynthetic process seems to be unaffected in L. minor plants among the tested dose rates. This study, supported by our earlier work, clearly indicates that plants shift from acclimation responses towards survival responses at increasing dose rates of ionising radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

Measurement of radon/thoron exhalation rates and gamma-ray dose rate in granite areas in Japan.

PubMed

Prasad, G; Ishikawa, T; Hosoda, M; Sahoo, S K; Kavasi, N; Sorimachi, A; Tokonami, S; Uchida, S

2012-11-01

Radon and thoron exhalation rates and gamma-ray dose rate in different places in Hiroshima Prefecture were measured. Exhalation rates were measured using an accumulation chamber method. The radon exhalation rate was found to vary from 3 to 37 mBq m(-2) s(-1), while the thoron exhalation rate ranged from 40 to 3330 mBq m(-2) s(-1). The highest radon exhalation rate (37 mBq m(-2) s(-1)) and gamma-ray dose rate (92 nGy h(-1)) were found in the same city (Kure City). In Kure City, indoor radon and thoron concentrations were previously measured at nine selected houses using a radon-thoron discriminative detector (Raduet). The indoor radon concentrations varied from 16 to 78 Bq m(-3), which was higher than the average value in Japan (15.5 Bq m(-3)). The indoor thoron concentration ranged from ND (not detected: below a detection limit of approximately 10 Bq m(-3)) to 314 Bq m(-3). The results suggest that radon exhalation rate from the ground is an influential factor for indoor radon concentration.

Evaluation of optimum room entry times for radiation therapists after high energy whole pelvic photon treatments.

PubMed

Ho, Lavine; White, Peter; Chan, Edward; Chan, Kim; Ng, Janet; Tam, Timothy

2012-01-01

Linear accelerators operating at or above 10 MV produce neutrons by photonuclear reactions and induce activation in machine components, which are a source of potential exposure for radiation therapists. This study estimated gamma dose contributions to radiation therapists during high energy, whole pelvic, photon beam treatments and determined the optimum room entry times, in terms of safety of radiation therapists. Two types of technique (anterior-posterior opposing and 3-field technique) were studied. An Elekta Precise treatment system, operating up to 18 MV, was investigated. Measurements with an area monitoring device (a Mini 900R radiation monitor) were performed, to calculate gamma dose rates around the radiotherapy facility. Measurements inside the treatment room were performed when the linear accelerator was in use. The doses received by radiation therapists were estimated, and optimum room entry times were determined. The highest gamma dose rates were approximately 7 μSv/h inside the treatment room, while the doses in the control room were close to background (~0 μSv/h) for all techniques. The highest personal dose received by radiation therapists was estimated at 5 mSv/yr. To optimize protection, radiation therapists should wait for up to11 min after beam-off prior to room entry. The potential risks to radiation therapists with standard safety procedures were well below internationally recommended values, but risks could be further decreased by delaying room entry times. Dependent on the technique used, optimum entry times ranged between 7 to 11 min. A balance between moderate treatment times versus reduction in measured equivalent doses should be considered.

Mating competitiveness of male Anopheles arabiensis mosquitoes irradiated with a partially or fully sterilizing dose in small and large laboratory cages.

PubMed

Helinski, M E H; Knols, B G J

2008-07-01

Male mating competitiveness is a crucial parameter in many genetic control programs including the sterile insect technique (SIT). We evaluated competitiveness of male Anopheles arabiensis Patton as a function of three experimental variables: (1) small or large cages for mating, (2) the effects of either a partially sterilizing (70 Gy) or fully sterilizing (120 Gy) dose, and (3) pupal or adult irradiation. Irradiated males competed for females with an equal number of unirradiated males. Competitiveness was determined by measuring hatch rates of individually laid egg batches. In small cages, pupal irradiation with the high dose resulted in the lowest competitiveness, whereas adult irradiation with the low dose gave the highest, with the latter males being equal in competitiveness to unirradiated males. In the large cage, reduced competitiveness of males irradiated in the pupal stage was more pronounced compared with the small cage; the males irradiated as adults at both doses performed similarly to unirradiated males. Unexpectedly, males irradiated with the high dose performed better in a large cage than in a small one. A high proportion of intermediate hatch rates was observed for eggs collected in the large cage experiments with males irradiated at the pupal stage. It is concluded that irradiation of adult An. arabiensis with the partially sterilizing dose results in the highest competitiveness for both cage designs. Cage size affected competitiveness for some treatments; therefore, competitiveness determined in laboratory experiments must be confirmed by releases into simulated field conditions. The protocols described are readily transferable to evaluate male competitiveness for other genetic control techniques.

Seasonal dynamics of nitrate and ammonium ion concentrations in soil solutions collected using MacroRhizon suction cups.

PubMed

Kabala, Cezary; Karczewska, Anna; Gałka, Bernard; Cuske, Mateusz; Sowiński, Józef

2017-07-01

The aims of the study were to analyse the concentration of nitrate and ammonium ions in soil solutions obtained using MacroRhizon miniaturized composite suction cups under field conditions and to determine potential nitrogen leaching from soil fertilized with three types of fertilizers (standard urea, slow-release urea, and ammonium nitrate) at the doses of 90 and 180 kg ha -1 , applied once or divided into two rates. During a 3-year growing experiment with sugar sorghum, the concentration of nitrate and ammonium ions in soil solutions was the highest with standard urea fertilization and the lowest in variants fertilized with slow-release urea for most of the months of the growing season. Higher concentrations of both nitrogen forms were noted at the fertilizer dose of 180 kg ha -1 . One-time fertilization, at both doses, resulted in higher nitrate concentrations in June and July, while dividing the dose into two rates resulted in higher nitrate concentrations between August and November. The highest potential for nitrate leaching during the growing season was in July. The tests confirmed that the miniaturized suction cups MacroRhizon are highly useful for routine monitoring the concentration of nitrate and ammonium ions in soil solutions under field conditions.

Dose rate estimation of the Tohoku hynobiid salamander, Hynobius lichenatus, in Fukushima.

PubMed

Fuma, Shoichi; Ihara, Sadao; Kawaguchi, Isao; Ishikawa, Takahiro; Watanabe, Yoshito; Kubota, Yoshihisa; Sato, Youji; Takahashi, Hiroyuki; Aono, Tatsuo; Ishii, Nobuyoshi; Soeda, Haruhi; Matsui, Kumi; Une, Yumi; Minamiya, Yukio; Yoshida, Satoshi

2015-05-01

The radiological risks to the Tohoku hynobiid salamanders (class Amphibia), Hynobius lichenatus due to the Fukushima Dai-ichi Nuclear Power Plant accident were assessed in Fukushima Prefecture, including evacuation areas. Aquatic egg clutches (n = 1 for each sampling date and site; n = 4 in total), overwintering larvae (n = 1-5 for each sampling date and site; n = 17 in total), and terrestrial juveniles or adults (n = 1 or 3 for each sampling date and site; n = 12 in total) of H. lichenatus were collected from the end of April 2011 to April 2013. Environmental media such as litter (n = 1-5 for each sampling date and site; n = 30 in total), soil (n = 1-8 for each sampling date and site; n = 31 in total), water (n = 1 for each sampling date and site; n = 17 in total), and sediment (n = 1 for each sampling date and site; n = 17 in total) were also collected. Activity concentrations of (134)Cs + (137)Cs were 1.9-2800, 0.13-320, and 0.51-220 kBq (dry kg) (-1) in the litter, soil, and sediment samples, respectively, and were 0.31-220 and <0.29-40 kBq (wet kg)(-1) in the adult and larval salamanders, respectively. External and internal absorbed dose rates to H. lichenatus were calculated from these activity concentration data, using the ERICA Assessment Tool methodology. External dose rates were also measured in situ with glass dosimeters. There was agreement within a factor of 2 between the calculated and measured external dose rates. In the most severely contaminated habitat of this salamander, a northern part of Abukuma Mountains, the highest total dose rates were estimated to be 50 and 15 μGy h(-1) for the adults and overwintering larvae, respectively. Growth and survival of H. lichenatus was not affected at a dose rate of up to 490 μGy h(-1) in the previous laboratory chronic gamma-irradiation experiment, and thus growth and survival of this salamander would not be affected, even in the most severely contaminated habitat in Fukushima Prefecture. However, further studies of the adult salamanders may be required in order to examine whether the most severe radioactive contamination has any effects on sensitive endpoints, since the estimated highest dose rate to the adults exceeded some of the guidance dose rates proposed by various organisations and programmes for the protection of amphibians, which range from 4 to 400 μGy h(-1). Conversely, at one site in Nakadori, a moderately contaminated region in Fukushima Prefecture, the dose rate to the adult salamanders in spring of 2012 was estimated to be 0.2 μGy h(-1). Estimated dose rates to the overwintering larvae in spring of 2012 were 1 and 0.2 μGy h(-1) at one site in Nakadori, and in Aizu, a less contaminated region in Fukushima Prefecture, respectively. These results suggest that there is a low risk that H. lichenatus will be affected by radioactive contamination in these districts, though further studies on dose rate estimation are required for definitive risk characterisation. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

Zohar, Sarah; O'Quigley, John

2006-01-01

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

Dactinomycin and Vincristine Toxicity in the Treatment of Childhood Cancer: A Retrospective Study from the Children’s Oncology Group

PubMed Central

Langholz, Bryan; Skolnik, Jeffrey M.; Barrett, Jeffrey S.; Renbarger, Jamie; Seibel, Nita L.; Zajicek, Anne; Arndt, Carola A.S.

2011-01-01

Background Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking. Methods Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical modeling was used to account for differences in AE data collection across studies, develop rate models for grade 3/4 CTCAE v3 hepatic- (AMD) and neuro- (AMD) toxicity, assess variation in toxicity rates over age and other factors, and predict toxicity risk under current dosing guidelines. Results For the same dose/body size, AMD toxicity rates were higher in patients <1 year than older patients and VCR toxicity rates increased with age. The statistical model provided estimates for AMD and VCR toxicity risk under current dosing schedules and indicated that patients of smaller body size were at lower risk of VCR toxicity than larger patients of the same age. The rate of AMD toxicity was highest early in treatment and was lower in patients who tolerated initial AMD without toxicity. Conclusion The observed decrease in AMD toxicity rate with cumulative dose may indicate sensitivity in a subgroup of patients while the observed increase in VCR toxicity risk with age may indicate changing sensitivity to VCR. Current dosing practices result in a fairly uniform toxicity profile within age group. However, PK/PD studies should be done to provide further provide further information on best dosing guidelines. PMID:21671362

Cryopreservation of common carp (Cyprinus carpio) sperm in 1.2 and 5 ml straws and occurrence of haploids among larvae produced with cryopreserved sperm.

PubMed

Horváth, Akos; Miskolczi, Edit; Mihálffy, Szilvia; Osz, Katalin; Szabó, Krisztián; Urbányi, Béla

2007-06-01

Experiments were carried out on the cryopreservation of common carp (Cyprinus carpio) sperm in order to test the suitability of using 1.2 and 5 ml straws and to investigate the ploidy of malformed larvae found among the hatched progeny. In the first set of experiments, the effect of freezing time was investigated on the hatch rate of embryos. The highest hatch rate for 1.2 ml straws was 69+/-16% at the freezing time of 4 min, and 39+/-27% for 5 ml straws at 5 min. In the second set, the effect different egg volumes fertilized with one straw of sperm on the hatch rate and the rate of malformed larvae was investigated. The highest hatch rate with 1.2 ml straws (86+/-12%) was observed when 10 g of eggs were fertilized with one straw, whereas with 5 ml straws the hatch rate was highest (65+/-18%) when 40 g of eggs were fertilized. The highest rate of malformed larvae (15+/-9%) was found in the control, whereas the highest rate of malformed larvae among the groups fertilized with cryopreserved sperm (13+/-7%) was found in the 1x dose group fertilized with 5 ml straw. The chromosome numbers of malformed larvae were investigated and haploids were found among those hatched from eggs fertilized with cryopreserved sperm whereas only diploids were found in the controls.

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

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

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

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

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s –1. At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution ofmore » diffracted intensity within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ~1.5–2 compared with those observed at conventional dose rates. As a result, improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Lifetimes and spatio-temporal response of protein crystals in intense X-ray microbeams

DOE PAGES

Warkentin, Matthew A.; Atakisi, Hakan; Hopkins, Jesse B.; ...

2017-10-13

Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s −1 . At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose. Non-exponential decays are a consequence of non-uniform illumination and the resulting spatial evolution of diffracted intensitymore » within the illuminated crystal volume. To quantify radiation-damage lifetimes and the damage state of diffracting crystal regions, a revised diffraction-weighted dose (DWD) is defined and it is shown that for Gaussian beams the DWD becomes nearly independent of actual dose at large doses. An apparent delayed onset of radiation damage seen in some intensity–dose curves is in fact a consequence of damage. Intensity fluctuations at high dose rates may arise from the impulsive release of gaseous damage products. Accounting for these effects, data collection at the highest dose rates increases crystal radiation lifetimes near 300 K (but not at 100 K) by a factor of ∼1.5–2 compared with those observed at conventional dose rates. Improved quantification and modeling of the complex spatio-temporal evolution of protein microcrystal diffraction in intense microbeams will enable more efficient data collection, and will be essential in improving the accuracy of structure factors and structural models.« less

Higher Risk Periods for Suicide Among VA Patients Receiving Depression Treatment

PubMed Central

Valenstein, Marcia; Kim, Hyungjin Myra; Ganoczy, Dara; McCarthy, John F.; Zivin, Kara; Austin, Karen L.; Hoggatt, Katherine; Eisenberg, Daniel; Piette, John D.; Blow, Frederic C.; Olfson, Mark

2010-01-01

Background Health systems with limited resources may have the greatest impact on suicide if their prevention efforts target the highest-risk treatment groups during the highest-risk periods. To date, few health systems have carefully segmented their depression treatment populations by level of risk and prioritized prevention efforts on this basis. Methods We conducted a retrospective cohort study of 887,859 VA patients receiving depression treatment between 4/1/1999 and 9/30/2004. We calculated suicide rates for five sequential 12-week periods following treatment events that health systems could readily identify: psychiatric hospitalizations, new antidepressant starts (>6 months without fills), “other” antidepressant starts, and dose changes. Using piecewise exponential models, we examined whether rates differed across time-periods. We also examined whether suicide rates differed by age-group in these periods. Results Over all time periods, the suicide rate was 114/100,000 person-years (95% CI; 108,120). In the first 12-week periods, suicide rates were: 568/100,000 p-y (95% CI; 493,651) following psychiatric hospitalizations; 210/100,000 p-y (95% CI; 187, 236) following new antidepressant starts; 193/100,000 p-y (95% CI; 167, 222) following other starts; and 154/100,000 p-y (95% CI; 133, 177) following dose changes. Suicide rates remained above the base rate for 48 weeks following hospital discharge and 12 weeks following antidepressant events. Adults aged 61–80 years were at highest risk in the first 12-weeks periods Conclusions To have the greatest impact on suicide, health systems should prioritize prevention efforts following psychiatric hospitalizations. If resources allow, closer monitoring may also be warranted in the first 12 weeks following antidepressant starts, across all age-groups. PMID:18945495

Evaluation of zinc oxide nanoparticle toxicity in sludge products applied to agricultural soil using multispecies soil systems.

PubMed

Fernández, María Dolores; Alonso-Blázquez, María Nieves; García-Gómez, Concepción; Babin, Mar

2014-11-01

To study the environmental impact of nanoparticles, the sludges of wastewater (WWTS) and water treatment (WTS) plants enriched with ZnO nanoparticles were added to agricultural soil, and the toxic effects of the nanoparticles were studied using a microcosm system based on the soil. The WWTS treated soils were characterised by statistically significant decreases (p<0.05) in Vicia sativa germination at the lowest (76.2%) and medium (95.2%) application rates, decreases in the fresh biomass for Triticum aestivum (19.5%), Raphanus sativus (64.1%), V. sativa (37.4%) and Eisenia fetida (33.6%) at the highest application rate and a dose-related significant increase (p<0.05) in earthworm mortality. In WTS amended soils, significant reductions (p<0.05) of the fresh biomass (17.2%) and the chlorophyll index (24.4%) for T. aestivum and the fresh biomass for R. sativus (31.4%) were only recorded at the highest application doses. In addition, the soil phosphatase enzymatic activity decreased significantly (p<0.05) in both WWTS (dose related) and WTS treatments. For water organisms, a slight inhibition of the growth of Chlorella vulgaris was observed (WWTS treated soils), along with statistically significant dose-related inhibition responses on total glutathione cell content, and statistically significant dose-related induction responses on the glutathione S-transferase enzyme activity and the reactive oxygen species generation on the RTG-2 fish cell line. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of UVB radiation on grazing of two cladocerans from high-altitude Andean lakes

PubMed Central

Rejas, Danny

2017-01-01

Climate change and water extraction may result in increased exposition of the biota to ultraviolet-B radiation (UVB) in high-altitude Andean lakes. Although exposition to lethal doses in these lakes is unlikely, sub-lethal UVB doses may have strong impacts in key compartments such as zooplankton. Here, we aimed at determining the effect of sub-lethal UVB doses on filtration rates of two cladoceran species (Daphnia pulicaria and Ceriodaphnia dubia). We firstly estimated the Incipient Limiting Concentration (ILC) and the Gut Passage Time (GPT) for both species. Thereafter we exposed clones of each species to four increasing UVB doses (treatments): i) DUV-0 (Control), ii) DUV-1 (0.02 MJ m2), iii) DUV-2 (0.03 MJ m2) and iv) DUV-3 (0.15 MJ m2); and estimated their filtration rates using fluorescent micro-spheres. Our results suggest that increasing sub-lethal doses of UVB radiation may strongly disturb the structure and functioning of high-altitude Andean lakes. Filtration rates of D. pulicaria were not affected by the lowest dose applied (DUV-1), but decreased by 50% in treatments DUV-2 and DUV-3. Filtration rates for C. dubia were reduced by more than 80% in treatments DUV-1 and DUV-2 and 100% of mortality occurred at the highest UVB dose applied (DUV-3). PMID:28379975

Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

PubMed

Abma, E; Peremans, K; De Vos, F; Bosmans, T; Kitshoff, A M; Daminet, S; Ni, Y; Dockx, R; de Rooster, H

2018-01-04

Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 μSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients. © 2018 John Wiley & Sons Ltd.

Development of a novel low-radiation-absorbent lok-bar to reduce X-ray scattering and absorption in RapidArc® treatment planning and dose delivery.

PubMed

Monzen, Hajime; Kubo, Kazuki; Tamura, Mikoto; Hayakawa, Masaru; Nishimura, Yasumasa

2017-05-01

We developed a novel low-radiation-absorbent lok-bar (HM-bar) that is used to secure the immobilizers to the couch. The aim of this study was to investigate the X-ray scattering and absorption properties of the HM-bar in computed tomography (CT) simulation and radiotherapy dose delivery using the Varian Exact™ lok-bar (VL-bar) as a benchmark. CT images were obtained with or without lok-bar, and then each image was visually evaluated for artifacts. The attenuation rates for each lok-bar were measured using a farmer-type ionization chamber (PTW30013) and the I'mRT phantom (IBA Dosimetry GmbH). Measurement points were between gantry angles of 110 and 180°. The treatment apparatus was a NovalisTx (Brainlab AG); X-ray energies were set at 6 MV and 10 MV. In the presence of each lok-bar, the radiation dose was measured in accordance with 10 volumetric modulated arc therapy-stereotactic body radiation therapy (VMAT-SBRT) plans for lung cancer. Artifacts were seldom observed in the CT scans of the HM-bar. The attenuation rate of each lok-bar was higher when the X-ray energy was set at 6 MV than at 10 MV. The highest attenuation rate in the VL-bar was observed at a gantry angle of 112°; the rates were 22.4% at 6 MV and 19.3% at 10 MV. Similarly, the highest attenuation rate for the HM-bar was also observed at a gantry angle of 112°; the rates were 12.2% and 10.1% at 6 MV and 10 MV, respectively. When the VL-bar was evaluated, the isocenter dose of the VMAT-SBRT plans was attenuated by 2.6% as a maximum case. In the case of the HM-bar, the maximum attenuation was 1.4%. In the measurements of each VMAT-SBRT plan, the difference of the dose attenuation rate between the VL-bar and HM-bar was approximately 1%. The HM-bar could be used to minimize the occurrence of artifacts and provide good images in CT scans regarding radiotherapy planning and dose calculation. It can be used for patient therapy at hospitals to provide accurate dose delivery because of its low X-ray scattering and absorption characteristics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

[The Dose Effect of Isocenter Selection during IMRT Dose Verification with the 2D Chamber Array].

PubMed

Xie, Chuanbin; Cong, Xiaohu; Xu, Shouping; Dai, Xiangkun; Wang, Yunlai; Han, Lu; Gong, Hanshun; Ju, Zhongjian; Ge, Ruigang; Ma, Lin

2015-03-01

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.

Inhalational and dermal exposures during spray application of biocides.

PubMed

Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

2005-01-01

Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a.s./h) and after-high-pressure applications in the antifouling sector (110-300 mg a.s./h). The potential dermal exposure of spray operators was lowest (dose rates from 0.2 to 7 mg a.s./h) in the areas of food and feed disinfection and private and public hygiene during spraying with low-pressure devices. During fogging, wood protection and antifouling applications, high-potential dermal exposures of the operators were determined. Dermal dose rates varied between 100 and 34,000 mg a.s./h.

Radiation Dose and Cancer Risk Estimates in 16-Slice Computed Tomography Coronary Angiography

PubMed Central

Einstein, Andrew J.; Sanz, Javier; Dellegrottaglie, Santo; Milite, Margherita; Sirol, Marc; Henzlova, Milena; Rajagopalan, Sanjay

2008-01-01

Background Recent advances have led to a rapid increase in the number of computed tomography coronary angiography (CTCA) studies performed. While several studies have reported effective dose (E), there is no data available on cancer risk for current CTCA protocols. Methods and Results E and organ doses were estimated, using scanner-derived parameters and Monte Carlo methods, for 50 patients having 16-slice CTCA performed for clinical indications. Lifetime attributable risks (LARs) were estimated with models developed in the National Academies’ Biological Effects of Ionizing Radiation VII report. E of a complete CTCA averaged 9.5 mSv, while that of a complete study, including calcium scoring when indicated, averaged 11.7 mSv. Calcium scoring increased E by 25%, while tube current modulation reduced it by 34% and was more effective at lower heart rates. Organ doses were highest to the lungs and female breast. LAR of cancer incidence from CTCA averaged approximately 1 in 1600, but varied widely between patients, being highest in younger women. For all patients, the greatest risk was from lung cancer. Conclusions CTCA is associated with non-negligible risk of malignancy. Doses can be reduced by careful attention to scanning protocol. PMID:18371595

The effect of variable-dose diazepam on dreaming and emergence phenomena in 400 cases of ketamine-fentanyl anaesthesia.

PubMed

Grace, R F

2003-09-01

This randomised double-blind field study compared 400 anaesthetics using diazepam (0, 0.025, 0.5, 0.1, 0.175 mg.kg-1) with ketamine (1 mg.kg-1) and fentanyl (1 microg.kg-1) in Melanesian patients. Dreams were very common and generally positive in nature. A minimum of 0.1 mg.kg-1 of diazepam was needed to significantly reduce dreaming when compared with water (67.5% vs. 94.6%; p < 0.0001), and to significantly lower median (95% CI) emergence delirium scores (4 (3-4) vs. 6 (5-7)). Gender and age did not affect the rate of dreaming. Increasing the dose of diazepam did not improve the dream experience. Patient satisfaction scores were similar between groups. Increases in blood pressure and heart rate were greater in dreamers than in non-dreamers. All groups had high rate-pressure products but this was highest when diazepam was not used. Higher diazepam doses significantly reduced the increase in blood pressure and heart rate at 3 and 6 min postketamine. When used with ketamine and fentanyl, 0.1 mg.kg-1 of diazepam has favourable psychic and cardiovascular effects. Lower diazepam doses generally had little effect whereas larger doses did not enhance the benefits further.

Dose assessment of digital tomosynthesis in pediatric imaging

NASA Astrophysics Data System (ADS)

Gislason, Amber; Elbakri, Idris A.; Reed, Martin

2009-02-01

We investigated the potential for digital tomosynthesis (DT) to reduce pediatric x-ray dose while maintaining image quality. We utilized the DT feature (VolumeRadTM) on the GE DefiniumTM 8000 flat panel system installed in the Winnipeg Children's Hospital. Facial bones, cervical spine, thoracic spine, and knee of children aged 5, 10, and 15 years were represented by acrylic phantoms for DT dose measurements. Effective dose was estimated for DT and for corresponding digital radiography (DR) and computed tomography (CT) patient image sets. Anthropomorphic phantoms of selected body parts were imaged by DR, DT, and CT. Pediatric radiologists rated visualization of selected anatomic features in these images. Dose and image quality comparisons between DR, DT, and CT determined the usefulness of tomosynthesis for pediatric imaging. CT effective dose was highest; total DR effective dose was not always lowest - depending how many projections were in the DR image set. For the cervical spine, DT dose was close to and occasionally lower than DR dose. Expert radiologists rated visibility of the central facial complex in a skull phantom as better than DR and comparable to CT. Digital tomosynthesis has a significantly lower dose than CT. This study has demonstrated DT shows promise to replace CT for some facial bones and spinal diagnoses. Other clinical applications will be evaluated in the future.

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation

NASA Astrophysics Data System (ADS)

Seed, T. M.; Fritz, T. E.; Tolle, D. V.; Jackson, W. E.

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d -1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d -1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (> 1yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d -1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d -1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.

Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil.

PubMed

Martins, Reinaldo de Menezes; Pavão, Ana Luiza Braz; de Oliveira, Patrícia Mouta Nunes; dos Santos, Paulo Roberto Gomes; Carvalho, Sandra Maria D; Mohrdieck, Renate; Fernandes, Alexandre Ribeiro; Sato, Helena Keico; de Figueiredo, Patricia Mandali; von Doellinger, Vanessa Dos Reis; Leal, Maria da Luz Fernandes; Homma, Akira; Maia, Maria de Lourdes S

2014-11-20

Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus. Copyright © 2014 Elsevier Ltd. All rights reserved.

A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE®

PubMed Central

von Krempelhuber, Alfred; Vollmar, Jens; Pokorny, Rolf; Rapp, Petra; Wulff, Niels; Petzold, Barbara; Handley, Amanda; Mateo, Lyn; Siersbol, Henriette; Kollaritsch, Herwig; Chaplin, Paul

2009-01-01

IMVAMUNE® is a Modified Vaccinia Ankara-based virus that is being developed as a safer 3rd generation smallpox vaccine. In order to determine the optimal dose for further development, a double-blind, randomized Phase II trial was performed testing three different doses of IMVAMUNE® in 164 healthy volunteers. All three IMVAMUNE® doses displayed a favourable safety profile, with local reactions as the most frequent observation. The 1×108 TCID50 IMVAMUNE® dose induced a total antibody response in 94% of the subjects following the first vaccination and the highest peak seroconversion rates by ELISA (100%) and PRNT (71%). This IMVAMUNE® dose was considered to be optimal for the further clinical development of this highly attenuated poxvirus as a safer smallpox vaccine. PMID:19944151

Prescription patterns of diuretics in Dutch community-dwelling elderly patients

PubMed Central

Van Kraaij, Dave J W; Jansen, René W M M; De Gier, Johan J; Gribnau, Frank W J; Hoefnagels, Willibrord H L

1998-01-01

Aims To describe age-and gender-related prescription patterns of diuretics in community-dwelling elderly, and to compare diuretics to other cardiovascular (CV) medications. Methods Cross-sectional study of patient-specific prescription data derived from a panel of 10 Dutch community pharmacies. Determination of proportional prescription rates and prescribed daily dose (PDD) of diuretics, cardiac glycosides, nitrates, angiotensin converting enzyme (ACE) inhibitors, β-adrenoceptor blockers, and calcium channel blockers in all 5326 patients aged 65 years or older dispensed CV medications between August 1st, 1995 and February 1st, 1996. Results Diuretics were prescribed to 2677 of 5326 patients (50.3%), 1325 patients (24.9%) using thiazides and 1198 patients (22.5%) using loop diuretics. Prescription rates of loop diuretics increased from 15.1% in patients aged 65–74 years to 37.2% in patients aged 85 years or older. Rates also increased for digoxin and nitrates. Rates for thiazide diuretics remained unchanged with age; rates for β-adrenoceptor blockers, ACE inhibitors and calcium channel blockers declined with age. Thiazides were prescribed to 30.1% of women compared with 16% of men (P<0.001). Average PDD was 135±117% of defined daily dose (DDD) for loop diuretics, and highest for bumetanide (245±2.01% of DDD, equivalent to 2.5±2.0 mg). Average PDD was 74±40% of DDD for thiazides, and highest for chlorthalidone (100±49% of DDD, equivalent to 25±12 mg). Conclusions Important characteristics of diuretic usage patterns in this elderly population were a steep increase in loop diuretic use in the oldest old, a large gender difference for thiazide use, and high prescribed doses for thiazides. PMID:9803990

Opioid Utilization and Opioid-Related Adverse Events in Non-Surgical Patients in U.S. Hospitals

PubMed Central

Herzig, Shoshana J.; Rothberg, Michael B.; Cheung, Michael; Ngo, Long H.; Marcantonio, Edward R.

2014-01-01

Background Recent studies in the outpatient setting have demonstrated high rates of opioid prescribing and overdose-related deaths. Prescribing practices in hospitalized patients are unexamined. Objective To investigate patterns and predictors of opioid utilization in non-surgical admissions to U.S. hospitals, variation in use, and the association between hospital-level use and rates of severe opioid-related adverse events. Design, Setting, and Patients Adult non-surgical admissions to 286 U.S. hospitals. Measurements Opioid exposure and severe opioid-related adverse events during hospitalization, defined using hospital charges and ICD-9-CM codes. Results Of 1.14 million admissions, opioids were used in 51%. The mean ± s.d. daily dose received in oral morphine equivalents (OME) was 68 ± 185 mg; 23% of exposed received a total daily dose of ≥ 100 mg OME. Opioid prescribing rates ranged from 5% in the lowest to 72% in the highest prescribing hospital (mean 51% ± 10%). After adjusting for patient characteristics, the adjusted opioid prescribing rates ranged from 33–64% (mean 50% ± s.d. 4%). Among exposed, 0.97% experienced severe opioid-related adverse events. Hospitals with higher opioid prescribing rates had higher adjusted relative risk of a severe opioid-related adverse event per patient exposed (RR 1.23 [1.14–1.33] for highest compared to lowest prescribing quartile). Conclusions The majority of hospitalized non-surgical patients were exposed to opioids, often at high doses. Hospitals that used opioids most frequently had increased adjusted risk of a severe opioid-related adverse event per patient exposed. Interventions to standardize and enhance the safety of opioid prescribing in hospitalized patients should be investigated. PMID:24227700

In vivo urethral dose measurements: a method to verify high dose rate prostate treatments.

PubMed

Brezovich, I A; Duan, J; Pareek, P N; Fiveash, J; Ezekiel, M

2000-10-01

Radiation doses delivered in high dose rate (HDR) brachytherapy are susceptible to many inaccuracies and errors, including imaging, planning and delivery. Consequently, the dose delivered to the patient may deviate substantially from the treatment plan. We investigated the feasibility of using TLD measurements in the urethra to estimate the discrepancy in treatments for prostate cancer. The dose response of the 1 mm diam, 6 mm long LiF rods that we used for the in vivo measurements was calibrated with the 192Ir HDR source, as well as a 60Co teletherapy unit. A train of 20 rods contained in a sterile plastic tube was inserted into the urethral (Foley) catheter for the duration of a treatment fraction, and the measured doses were compared to the treatment plan. Initial results from a total of seven treatments in four patients show good agreement between theory and experiment. Analysis of any one treatment showed agreement within 11.7% +/- 6.2% for the highest dose encountered in the central prostatic urethra, and within 10.4% +/- 4.4% for the mean dose. Taking the average over all seven treatments shows agreement within 1.7% for the maximum urethral dose, and within 1.5% for the mean urethral dose. Based on these initial findings it seems that planned prostate doses can be accurately reproduced in the clinic.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

PubMed

Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

2011-01-01

The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

Estimation of absorbed radiation dose rates in wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi nuclear power plant accident.

PubMed

Kubota, Yoshihisa; Takahashi, Hiroyuki; Watanabe, Yoshito; Fuma, Shoichi; Kawaguchi, Isao; Aoki, Masanari; Kubota, Masahide; Furuhata, Yoshiaki; Shigemura, Yusaku; Yamada, Fumio; Ishikawa, Takahiro; Obara, Satoshi; Yoshida, Satoshi

2015-04-01

The dose rates of radiation absorbed by wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi Nuclear Power Plant accident were estimated. The large Japanese field mouse (Apodemus speciosus), also called the wood mouse, was the major rodent species captured in the sampling area, although other species of rodents, such as small field mice (Apodemus argenteus) and Japanese grass voles (Microtus montebelli), were also collected. The external exposure of rodents calculated from the activity concentrations of radiocesium ((134)Cs and (137)Cs) in litter and soil samples using the ERICA (Environmental Risk from Ionizing Contaminants: Assessment and Management) tool under the assumption that radionuclides existed as the infinite plane isotropic source was almost the same as those measured directly with glass dosimeters embedded in rodent abdomens. Our findings suggest that the ERICA tool is useful for estimating external dose rates to small animals inhabiting forest floors; however, the estimated dose rates showed large standard deviations. This could be an indication of the inhomogeneous distribution of radionuclides in the sampled litter and soil. There was a 50-fold difference between minimum and maximum whole-body activity concentrations measured in rodents at the time of capture. The radionuclides retained in rodents after capture decreased exponentially over time. Regression equations indicated that the biological half-life of radiocesium after capture was 3.31 d. At the time of capture, the lowest activity concentration was measured in the lung and was approximately half of the highest concentration measured in the mixture of muscle and bone. The average internal absorbed dose rate was markedly smaller than the average external dose rate (<10% of the total absorbed dose rate). The average total absorbed dose rate to wild rodents inhabiting the sampling area was estimated to be approximately 52 μGy h(-1) (1.2 mGy d(-1)), even 3 years after the accident. This dose rate exceeds 0.1-1 mGy d(-1) derived consideration reference level for Reference rat proposed by the International Commission on Radiological Protection (ICRP). Copyright © 2015 Elsevier Ltd. All rights reserved.

Image processing techniques revealing the relationship between the field-measured ambient gamma dose equivalent rate and geological conditions at a granitic area, Velence Mountains, Hungary

NASA Astrophysics Data System (ADS)

Beltran Torres, Silvana; Petrik, Attila; Zsuzsanna Szabó, Katalin; Jordan, Gyozo; Szabó, Csaba

2017-04-01

In order to estimate the annual dose that the public receive from natural radioactivity, the identification of the potential risk areas is required which, in turn, necessitates understanding the relationship between the spatial distribution of natural radioactivity and the geogenic risk factors (e.g., rock types, dykes, faults, soil conditions, etc.). A detailed spatial analysis of ambient gamma dose equivalent rate was performed in the western side of Velence Mountains, the largest outcropped granitic area in Hungary. In order to assess the role of local geology in the spatial distribution of ambient gamma dose rates, field measurements were carried out at ground level at 300 sites along a 250 m x 250 m regular grid in a total surface of 14.7 km2. Digital image processing methods were applied to identify anomalies, heterogeneities and spatial patterns in the measured gamma dose rates, including local maxima and minima determination, digital cross sections, gradient magnitude and gradient direction, second derivative profile curvature, local variability, lineament density, 2D autocorrelation and directional variogram analyses. Statistical inference showed that different gamma dose rate levels are associated with the rock types (i.e., Carboniferous granite, Pleistocene colluvial, proluvial, deluvial sediments and talus, and Pannonian sand and pebble), with the highest level on the Carboniferous granite including outlying values. Moreover, digital image processing revealed that linear gamma dose rate spatial features are parallel to the SW-NE dyke system and possibly to the NW-SE main fractures. The results of this study underline the importance of understanding the role of geogenic risk factors influencing the ambient gamma dose rate received by public. The study also demonstrates the power of the image processing techniques for the identification of spatial pattern in field-measured geogenic radiation.

Pharmacological evaluation for anticancer and immune activities of a novel polysaccharide isolated from Boletus speciosus Frost.

PubMed

Hou, Yiling; Ding, Xiang; Hou, Wanru; Song, Bo; Wang, Ting; Wang, Fang; Li, Jian; Zeng, Yichun; Zhong, Jie; Xu, Ting; Zhu, Hongqing

2014-04-01

The fungal polysaccharides have been revealed to exhibit a variety of biological activities, including antitumor, immune-stimulation and antioxidation activities. In the present study, the immune and anticancer activities of a novel polysaccharide, BSF-A, isolated from Boletus speciosus Frost was investigated. The inhibitory rate of S180 tumors in mice treated with 40 mg/kg BSF-A reached 62.449%, which was the highest rate from the three doses administered; this may be comparable to mannatide. The antitumor activity of BSF-A is commonly considered to be a consequence of the stimulation of the cell-mediated immune response, as it may significantly promote the macrophage cells in the dose range of 100-400 µg/ml in vitro. The levels of the cytokines, IL-6, IL-1β and TNF-α, and nitric oxide, induced by BSF-A treatment at varying concentrations in the macrophage cells were similar to the levels in the cells treated with lipopolysaccharide. There was weak expression of the TNF-α, IL-6, IL-1β and inducible nitric oxide synthase mRNA in the untreated macrophages, but this increased significantly in a dose-dependent manner in the BSF-A-treated cells. BSF-A also had a time- and dose-dependent effect on the growth inhibition of the Hep-2 cells, with the concentration of 400 µg/ml having the highest inhibitory rate. A quantitative PCR array analysis of the gene expression profiles indicated that BSF-A had anticancer activities that affected cell apoptosis in the Hep-2 cells. The results obtained in the present study indicated that the purified polysaccharide of Boletus speciosus Frost is a potential source of natural anticancer substances.

Expression of Genes Associated with DNA Damage Sensing in Human Fibroblasts Exposed to Low-dose-rate Gamma Rays

NASA Technical Reports Server (NTRS)

Zhang, Ye; Mehta, Satish; Hammond, Diane; Pierson, Duane; Jeevarajan, Antony; Cucinotta, Francis; Rohde, Larry; Wu, Honglu

2007-01-01

Understanding of the molecular response to low-dose and low-dose-rate radiation exposure is essential for the extrapolation of high-dose radiation risks to those at dose levels relevant to space and other environmental concerns. Most of the reported studies of gene expressions induced by low-dose or low-dose-rate radiation were carried out on exponentially growing cells. In the present study, we analyzed expressions of 84 genes associated with DNA damage sensing using real time PCR in human fibroblasts in mostly G1 phase of the cell cycle. The cells were exposed continuously to gamma rays at a dose rate of 0.8 cGy/hr for 1, 2, 6 or 24 hrs at 37 C throughout the exposure. The total RNA was isolated immediately after the exposure was terminated. Of the 84 genes, only a few showed significant changes of the expression level. Some of the genes (e.g. DDit3 and BTG2) were found to be up or down regulated only after a short period of exposure, while other genes (e.g. PRKDC) displayed a highest expression level at the 24 hr time point. The expression profiles for the exposed cells which had a smaller portion of G1 cells indicated more cell cycle signaling and DNA repair genes either up or down regulated. Interestingly, the panel of genes changed from radiation exposure in G1 cells is different from the panel in cells having less G1 arrest cells. The gene expression profile of the cells responding to low-dose-radiation insult apparently depends on the cell growth stage. The response pathway in G1 cells may differ from that in exponentially growing cells.

Experience with rufinamide in a pediatric population: a single center's experience.

PubMed

Vendrame, Martina; Loddenkemper, Tobias; Gooty, Vasu D; Takeoka, Masanori; Rotenberg, Alexander; Bergin, Ann M; Eksioglu, Yaman Z; Poduri, Annapurna; Duffy, Frank H; Libenson, Mark; Bourgeois, Blaise F; Kothare, Sanjeev V

2010-09-01

Rufinamide is a new antiepileptic drug recently approved as adjunctive treatment for generalized seizures in Lennox-Gastaut syndrome. We undertook a retrospective analysis of 77 patients with refractory epilepsy and receiving rufinamide to evaluate the drug's efficacy, tolerability, safety, and dosing schedules. It appeared efficacious in diverse epilepsy syndromes, with the highest responder rate in focal cryptogenic epilepsies (81.1% of patients with >50% response rate), and in diverse seizure types, with the highest responder rate in tonic/atonic and partial seizures (48.6% and 46.7% of patients with >50% response rate, respectively). Rufinamide was well tolerated: only 13% of patients developed side effects necessitating drug withdrawal. These findings suggest that rufinamide may possess good efficacy and tolerability, and that its efficacy may extend to epilepsy syndromes beyond Lennox-Gastaut, including both partial and generalized epilepsy syndromes. Copyright 2010 Elsevier Inc. All rights reserved.

Ultraviolet-visible and fluorescence spectroscopy can be used as a diagnostic tool for gamma irradiation detection in vivo.

PubMed

K-Abdelhalim, Mohamed Anwar; Moussa, Sherif A-Abdelmottaleb

2016-09-01

The spectroscopic properties can indicate important features about the nature and severity of the disease. However, no earlier studies have been used the spectroscopic properties as a diagnostic tool for radiation detection. This study was aimed to use ultraviolet-visible and fluorescence spectroscopy as a diagnostic tool for gamma irradiation detection in rats in vivo. Adult male rats were exposed to 25, 50, 75 and 100 Gray as single dose, using Cobalt-60 (Co-60) source with a dose rate of 0.883 centi Gray/sec (cGy/s). Ultraviolet and fluorescence spectroscopy of rat's blood serum were measured. After gamma irradiation of rats in vivo, the blood serum absorbance peaks for 25, 50, 75 and 100 Gray (Gy) decreased and shifted towards the ultra violet wavelength. A maximal change in fluorescence intensity of blood serum at 350 nm was obtained when exciting light at 194 nm after irradiation. The fluorescence intensity also decreased with the dose. The highest radiation gamma dose might be accompanied with the highest oxidative stress. This study suggests that at the above mentioned gamma radiation doses, the blood is highly fragmented; with low aggregation at 25 Gy and with high aggregation at 50-100 Gy.

Effect of chronic d-fenfluramine administration on rat hypothalamic serotonin levels and release

NASA Technical Reports Server (NTRS)

Schaechter, Judith D.; Wurtman, Richard J.

1988-01-01

D-fenfluramine, an anorectic agent in rats and man, was administered daily at doses 1.25, 2.5, 5, or 10 mg/kg/day for 10 days, and sacrificed 6 days later. Hypothalamic serotonin (5-HT) levels were unchanged in rats receiving 1.25-5 mg/kg/day of d-fenfluramine but reduced by 22 percent (p less than 0.01) at the highest drug dose (10 mg/kg/day); hypothalamic 5-hydroxyindole acetic acid (5-HIAA) levels were reduced by 15 percent (p less than 0.05) or 28 percent (p less than 0.01) in rats receiving 5 or 10 mg/kg/day of the drug, respectively. Hypothalamic slices prepared from rats which were previously treated with any of the drug doses spontaneously released endogenous 5-HT at rates that did not differ from those of vehicle-treated rats. 5-HT released with electrical field-stimulation was unaffected by prior d-fenfluramine treatment at doses of 1.25-5 mg/kg/day, and was reduced by 20 percent (p less than 0.05) from slices prepared from rats which received 10 mg/kg/day. 5-HIAA efflux was also attenuated by the highest drug dose. These data indicate that chronic administration to rats of customary anorectic doses of d-fenfluramine (i.e. 0.06-1.25 mg/kg) fail to cause long-lasting reductions in brain 5-HT release.

Ingestion dose from 238U, 232Th, 226Ra, 40K and 137Cs in cereals, pulses and drinking water to adult population in a high background radiation area, Odisha, India.

PubMed

Lenka, Pradyumna; Sahoo, S K; Mohapatra, S; Patra, A C; Dubey, J S; Vidyasagar, D; Tripathi, R M; Puranik, V D

2013-03-01

A natural high background radiation area is located in Chhatrapur, Odisha in the eastern part of India. The inhabitants of this area are exposed to external radiation levels higher than the global average background values, due to the presence of uranium, thorium and its decay products in the monazite sands bearing placer deposits in its beaches. The concentrations of (232)Th, (238)U, (226)Ra, (40)K and (137)Cs were determined in cereals (rice and wheat), pulses and drinking water consumed by the population residing around this region and the corresponding annual ingestion dose was calculated. The annual ingestion doses from cereals, pulses and drinking water varied in the range of 109.4-936.8, 10.2-307.5 and 0.5-2.8 µSv y(-1), respectively. The estimated total annual average effective dose due to the ingestion of these radionuclides in cereals, pulses and drinking water was 530 µSv y(-1). The ingestion dose from cereals was the highest mainly due to a high consumption rate. The highest contribution of dose was found to be from (226)Ra for cereals and drinking water and (40)K was the major dose contributor from the intake of pulses. The contribution of man-made radionuclide (137)Cs to the total dose was found to be minimum. (226)Ra was found to be the largest contributor to ingestion dose from all sources.

Musculoskeletal imaging with a prototype photon-counting detector.

PubMed

Gruber, M; Homolka, P; Chmeissani, M; Uffmann, M; Pretterklieber, M; Kainberger, F

2012-01-01

To test a digital imaging X-ray device based on the direct capture of X-ray photons with pixel detectors, which are coupled with photon-counting readout electronics. The chip consists of a matrix of 256 × 256 pixels with a pixel pitch of 55 μm. A monolithic image of 11.2 cm × 7 cm was obtained by the consecutive displacement approach. Images of embalmed anatomical specimens of eight human hands were obtained at four different dose levels (skin dose 2.4, 6, 12, 25 μGy) with the new detector, as well as with a flat-panel detector. The overall rating scores for the evaluated anatomical regions ranged from 5.23 at the lowest dose level, 6.32 at approximately 6 μGy, 6.70 at 12 μGy, to 6.99 at the highest dose level with the photon-counting system. The corresponding rating scores for the flat-panel detector were 3.84, 5.39, 6.64, and 7.34. When images obtained at the same dose were compared, the new system outperformed the conventional DR system at the two lowest dose levels. At the higher dose levels, there were no significant differences between the two systems. The photon-counting detector has great potential to obtain musculoskeletal images of excellent quality at very low dose levels.

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

Einck, John P., E-mail: jeinck@ucsd.edu; Hudson, Alana; Shulman, Adam C.

West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single {sup 60}Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in themore » developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.« less

Adenoid cystic salivary gland carcinoma: treatment with irradiation and surgery

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

Simpson, J.R.; Thawley, S.E.; Matsuba, H.M.

1984-05-01

The recrods of 71 patients with adenoid cystic carcinoma of the salivary glands were reviewed to determine the dose response relationships for this aggressive tumor. Local control after treament was determined for all patients and analyzed with respect to extent of surgery and dose of radiation. Of 70 patients who were available for evaluation of local control, 28 (40%) had a local recurrence and 42 (60%) did not. The highest control rates were found in patients who underwent both radiation therapy and surgery. Patients who received a dose equal to or greater than 6,000 rad (60 Gy) in addition tomore » surgery had significantly higher local control rates than those who received less than 6,000 rad (60 Gy). Distant metastases developed in 50% of patients regardless of local control, with the following distribution: 39% lung, 19% bone, and 10% disseminated soft-tissue metastases.« less

Renal Drug Dosing

PubMed Central

Vogel, Erin A.; Billups, Sarah J.; Herner, Sheryl J.

2016-01-01

Summary Objective The purpose of this study was to compare the effectiveness of an outpatient renal dose adjustment alert via a computerized provider order entry (CPOE) clinical decision support system (CDSS) versus a CDSS with alerts made to dispensing pharmacists. Methods This was a retrospective analysis of patients with renal impairment and 30 medications that are contraindicated or require dose-adjustment in such patients. The primary outcome was the rate of renal dosing errors for study medications that were dispensed between August and December 2013, when a pharmacist-based CDSS was in place, versus August through December 2014, when a prescriber-based CDSS was in place. A dosing error was defined as a prescription for one of the study medications dispensed to a patient where the medication was contraindicated or improperly dosed based on the patient’s renal function. The denominator was all prescriptions for the study medications dispensed during each respective study period. Results During the pharmacist- and prescriber-based CDSS study periods, 49,054 and 50,678 prescriptions, respectively, were dispensed for one of the included medications. Of these, 878 (1.8%) and 758 (1.5%) prescriptions were dispensed to patients with renal impairment in the respective study periods. Patients in each group were similar with respect to age, sex, and renal function stage. Overall, the five-month error rate was 0.38%. Error rates were similar between the two groups: 0.36% and 0.40% in the pharmacist- and prescriber-based CDSS, respectively (p=0.523). The medication with the highest error rate was dofetilide (0.51% overall) while the medications with the lowest error rate were dabigatran, fondaparinux, and spironolactone (0.00% overall). Conclusions Prescriber- and pharmacist-based CDSS provided comparable, low rates of potential medication errors. Future studies should be undertaken to examine patient benefits of the prescriber-based CDSS. PMID:27466041

Radiation dose to patients and image quality evaluation from coronary 256-slice computed tomographic angiography

NASA Astrophysics Data System (ADS)

Chen, Liang-Kuang; Wu, Tung-Hsin; Yang, Ching-Ching; Tsai, Chia-Jung; Lee, Jason J. S.

2010-07-01

The aim of this study is to assess radiation dose and the corresponding image quality from suggested CT protocols which depends on different mean heart rate and high heart rate variability by using 256-slice CT. Fifty consecutive patients referred for a cardiac CT examination were included in this study. All coronary computed tomographic angiography (CCTA) examinations were performed on a 256-slice CT scanner with one of five different protocols: retrospective ECG-gating (RGH) with full dose exposure in all R-R intervals (protocol A), RGH of 30-80% pulsing window with tube current modulation (B), RGH of 78±5% pulsing window with tube current modulation (C), prospective ECG-triggering (PGT) of 78% R-R interval with 5% padding window (D) and PGT of 78% R-R interval without padding window (E). Radiation dose parameters and image quality scoring were determined and compared. In this study, no significant differences were found in comparison on image quality of the five different protocols. Protocol A obtained the highest radiation dose comparing with those of protocols B, C, D and E by a factor of 1.6, 2.4, 2.5 and 4.3, respectively ( p<0.001), which were ranged between 2.7 and 11.8 mSv. The PGT could significantly reduce radiation dose delivered to patients, as compared to the RGH. However, the use of PGT has limitations and is only good in assessing cases with lower mean heart rate and stable heart rate variability. With higher mean heart rate and high heart rate variability circumstances, the RGH within 30-80% of R-R interval pulsing window is suggested as a feasible technique for assessing diagnostic performance.

EFFECTS OF CHRONIC IRRADIATION ON EINKORN WHEAT (in Japanese)

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

Matsumura, S.; Fujii, T.

1963-01-01

An experiment was carried out with seedlings of einkorn wheat ( Triticum monococcum flavescens), planted at the stage of 3 to 4 foilage leaves on Feb 23rd at several distances from the source and irradiated with varying dose rates and dosages. The plants wer irradiated during their growth and harvested on June 21st. Regular irradiation followed the routine of the gamma field; that is it was applied 20 hr per day starting from April 1st, but before that time, irradiation was occasionally given for mearsurement of dosage or dose rates and checks of the apparatus. Therefore, total irradiation time frommore » planting to harvest amounted to 1843 hours. Total dosages were calculated as 369 r minimum and 4608 r maximum, intensity being 4 to 50 r/20 hr. Survival rate clearly decreased at the highest dosage, while there was no marked difference between the other five irradiated lots and the nonirradiated one. On the other hand, seed fertility was nonlinearly (gradually at higher dosages) decreased with increasing dosage and reached to about one-half of that of the control lot at the highest dosage. For comparison, seedlings of the same kind were irradiated by 0.5 and 1 kr acute gamma rays (1 kr/hr) 16 days after sowing. Survival rate and fertility markedly decreased at 1-kr irradiation. The results were not easily comparable with those of chronic irradiation because acute irradiation was done only in the early seedling stage. Acute 1-kr irradiation showed severe effects and a similar effect was seen at the highest dosage of chronic irradiation (4607 r). Thus, the plants must be more tolerant to higher dosage when radiation intensity is low. (P.C.H.)« less

Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs)

PubMed Central

Sable, Helen J. K.; Monaikul, Supida; Poon, Emily; Eubig, Paul A.; Schantz, Susan L.

2010-01-01

Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest developmental PCB exposure can alter the interoceptive cues of psychostimulants. PMID:20933596

Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; LeSage, Mark G.

2013-01-01

Rationale The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective To use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods Rats were trained for NSA during daily 23 hr sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23 hr sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID:19475400

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation.

PubMed

Seed, T M; Fritz, T E; Tolle, D V; Jackson, W E

2002-01-01

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation. Published by Elsevier Science Ltd on behalf of COSPAR.

Adverse events following school-based vaccination of girls with quadrivalent human papillomavirus vaccine in Slovenia, 2009 to 2013.

PubMed

Šubelj, Maja; Učakar, Veronika; Kraigher, Alenka; Klavs, Irena

2016-01-01

Adverse events following immunisation (AEFIs) with qHPV reported to the Slovenian AEFI Registry for the first four school years of the vaccination programme were analysed. We calculated annual reporting rates for 11-14 year-old vaccinees with AEFIs, using the number of qHPV doses distributed within the school-based vaccination programme as the denominator. Between September 2009 and August 2013, 211 AEFIs that occurred in 89 vaccinees were reported, a rate of 149.5 vaccinees with AEFI per 100,000 qHPV doses distributed. For five vaccinees, serious AEFIs (8.4 per 100,000 doses distributed) were reported. The highest reporting rates were for fatigue, headache, and fever (≥ 38.0⁰) (53.8, 40.3, and 35.3 per 100,000 qHPV doses distributed, respectively). As no AEFI resulted in permanent sequelae and they all were categorised as serious only due to the criterion of a minimum of one day of hospitalisation, this provides reassurance for the safety of our school-based HPV vaccination programme. Further AEFI surveillance is warranted to provide data for HPV vaccination programme monitoring and evaluation of its safety.

Diabetes and cardiometabolic risk factors in Cambodia: Results from two screening studies.

PubMed

Wagner, Julie; Naranjo, Diana; Khun, Touch; Seng, Serey; Horn, Ien S; Suttiratana, Sakinah C; Keuky, Lim

2018-02-01

Despite growing attention to diabetes throughout Asia, data from Southeast Asia are limited. This article reports rates of diabetes, hypertension, and obesity in Cambodia. Two studies were conducted across different regions of Cambodia: (i) a 2012 screening study across urban, semi-urban, and rural areas that used point-of-care capillary glucose for determination of diabetes (n = 13 997); and (ii) a 2005 epidemiological study with random selection from two main urban areas that used oral glucose tolerance tests for determination of diabetes (n = 1863). Blood pressure and anthropometrics were also measured. In the screening study, rates of diabetes were significantly higher in urban than rural sites, with intermediate rates in semi-urban areas. There was a significant dose-response effect for urbanicity on overweight, obesity, and waist:hip ratio, with higher rates for urban versus semi-urban and for semi-urban versus rural locales. Rural sites had the lowest rates of hypertension, followed by urban and semi-urban sites. Among people who screened positive for diabetes, there was a dose-response effect for urbanicity on undiagnosed diabetes; rates of previously undiagnosed diabetes were lowest in urban (51%), followed by semi-urban (55%) and rural (67%) locales. Rural participants reported the highest rates of smoking and alcohol use. In the urban epidemiological study, prevalence rates of diabetes and impaired glucose tolerance were approximately 10%, indicating a prevalence of total glucose intolerance of approximately 20%. In Cambodia, diabetes rates are high among urban residents and undiagnosed diabetes is highest among rural residents. A country-wide public health response is urgently needed; as development continues, rates of diabetes are expected to rise. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

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

DOE PAGES

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

2016-07-26

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

Dosimetric results on EURECA

NASA Technical Reports Server (NTRS)

Reitz, G.

1995-01-01

Detector packages were exposed on the European Retrievable Carrier (EURECA) as part of the Biostack experiment inside the Exobiology and Radiation Assembly (ERA) and at several locations around EURECA. The packages consist of different plastic nuclear track detectors, nuclear emulsions and thermoluminescence dosimeters (TLD's). Evaluation of these detectors yields data on absorbed dose and particle and LET spectra. Preliminary results of absorbed dose measurements in the EURECA dosimeter packages are reported and compared to results of the LDEF experiments. The highest dose rate measured on EURECA is 63.3 plus or minus 0.4 mGy d(exp -1) behind a shielding thickness of 0.09 g cm(exp -2) in front of the detector package.

No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight

PubMed Central

Smith, Daniel L.; Robertson, Henry; Desmond, Renee; Nagy, Tim R.; Allison, David B.

2010-01-01

Objective The health and longevity effects of body weight reduction resulting from exercise and caloric restriction in rodents are well known, but less is known about whether similar effects occur with weight reduction from the use of a pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake inhibitor. Results & Conclusion Using data from a two-year toxicology study of sibutramine in CD rats and CD-1 mice, despite a dose-dependent reduction in food intake and body weight in rats compared to controls, and a body weight reduction in mice at the highest dose, there was no compelling evidence for reductions in mortality rate. PMID:21079617

Field-evolved resistance to λ-cyhalothrin in the lady beetle Eriopis connexa.

PubMed

Costa, P M G; Torres, J B; Rondelli, V M; Lira, R

2018-06-01

Natural enemies are exposed to insecticide sprays for herbivorous species and may evolve field resistance to insecticides. Natural enemies selected for resistance in the field, however, are welcome for pest control. The susceptibility of 20 populations of Eriopis connexa from various crop ecosystems to λ-cyhalothrin was tested. Three bioassays were conducted: (i) topical treatment with lethal dose (LD)50 previously determined for populations considered standard for susceptibility (LD50S) and for resistance (LD50R) to λ-cyhalothrin at technical grade; (ii) dose-mortality assay to calculate the LD for populations exhibiting significant survival to the LD50R; and (iii) determination of survival when exposed to dried residues at field rates. Among the 20 tested populations, seven populations did not survive or survival rates were lower than 10% when treated with LD50R; three populations survived >20%, but lower than 50%; while ten populations exhibited equal or greater survival rates compared with the 50% expected survival for the LD50R. Thus, these ten populations were subjected to dose-mortality response, and the LD50 values varied from 0.046 to 5.44 µg a.i./insect with resistance ratio of 8.52- to 884.08-folds. Adults from these ten populations that were ranked as resistant according to the LD50R exhibited survival from 44.5 to 100% exposed to the lowest and from 38.8 to 100% exposed to the highest field rates of λ-cyhalothrin, respectively. Otherwise, the remaining ten populations ranked as susceptible according to the LD50R showed survival from 3.3 to 56% exposed to the lowest and from 0 to 17.7% exposed to the highest field rates of λ-cyhalothrin, respectively. Therefore, 50% of the tested E. connexa populations exhibited field-evolved resistance to λ-cyhalothrin and the use of a discriminatory LD50 for resistance matched the survival obtained when exposed to the insecticide field rates.

Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: is low incidence of regional failure due to incidental nodal irradiation?

PubMed

Chen, Ming; Hayman, James A; Ten Haken, Randall K; Tatro, Daniel; Fernando, Shaneli; Kong, Feng-Ming

2006-01-01

To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of > or = 40 Gy, respectively. Less than 10% of all other nodal regions received a dose of > or = 40 Gy. No patients failed initially at nodal sites. Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation.

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

Sun, Li-Min, E-mail: limin.sun@yahoo.com; Huang, Chih-Jen; Faculty of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan

Acute skin reaction during adjuvant radiotherapy for breast cancer is an inevitable process, and its severity is related to the skin dose. A high–skin dose area can be speculated based on the isodose distribution shown on a treatment planning. To determine whether treatment planning can reflect high–skin dose location, 80 patients were collected and their skin doses in different areas were measured using a thermoluminescent dosimeter to locate the highest–skin dose area in each patient. We determined whether the skin dose is consistent with the highest-dose area estimated by the treatment planning of the same patient. The χ{sup 2} andmore » Fisher exact tests revealed that these 2 methods yielded more consistent results when the highest-dose spots were located in the axillary and breast areas but not in the inframammary area. We suggest that skin doses shown on the treatment planning might be a reliable and simple alternative method for estimating the highest skin doses in some areas.« less

Biological effects of α-radiation exposure by (241)Am in Arabidopsis thaliana seedlings are determined both by dose rate and (241)Am distribution.

PubMed

Biermans, Geert; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Saenen, Eline; Van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

2015-11-01

Human activity has led to an increasing amount of radionuclides in the environment and subsequently to an increased risk of exposure of the biosphere to ionising radiation. Due to their high linear energy transfer, α-emitters form a threat to biota when absorbed or integrated in living tissue. Among these, (241)Am is of major concern due to high affinity for organic matter and high specific activity. This study examines the dose-dependent biological effects of α-radiation delivered by (241)Am at the morphological, physiological and molecular level in 14-day old seedlings of Arabidopsis thaliana after hydroponic exposure for 4 or 7 days. Our results show that (241)Am has high transfer to the roots but low translocation to the shoots. In the roots, we observed a transcriptional response of reactive oxygen species scavenging and DNA repair pathways. At the physiological and morphological level this resulted in a response which evolved from redox balance control and stable biomass at low dose rates to growth reduction, reduced transfer and redox balance decline at higher dose rates. This situation was also reflected in the shoots where, despite the absence of a transcriptional response, the control of photosynthesis performance and redox balance declined with increasing dose rate. The data further suggest that the effects in both organs were initiated in the roots, where the highest dose rates occurred, ultimately affecting photosynthesis performance and carbon assimilation. Though further detailed study of nutrient balance and (241)Am localisation is necessary, it is clear that radionuclide uptake and distribution is a major parameter in the global exposure effects on plant performance and health. Copyright © 2015 Elsevier Ltd. All rights reserved.

The dependence of the growth rate and meat content of young boars on semen parameters and conception rate.

PubMed

Knecht, D; Jankowska-Mąkosa, A; Duziński, K

2017-05-01

Boars have a decisive impact on the progress in pig production, however, there is no recent information about the optimal growth parameters during the rearing period for modern breed later used in artificial insemination (AI) stations. Therefore, the objective of the research was to conduct semen parameter and conception rate analyses on the basis of growth rate and meat content assessments made during the rearing of AI boars of different genotypes. The study was carried out between 2010 and 2014 and included 184 boars in five breed combinations: 46 Polish Large White, 50 Polish Landrace, 27 Pietrain, 36 Duroc×Pietrain and 25 Hampshire×Pietrain. Boars were qualified by daily gains and meat content assessment (between 170 and 210 days of life). A total number of 38 272 ejaculates were examined (semen volume (ml), spermatozoa concentration (×106 ml-1), total number of spermatozoa (×109) and number of insemination doses from one ejaculate (n)). The fertility was determined by the conception rate (%). Semen volume, spermatozoa concentration and conception rate (P<0.01), followed by the total number of spermatozoa and insemination doses (P<0.05) were characterized by the highest variability in relation to breed of boars. The effect of daily gains was reported for spermatozoa concentration, number of insemination doses, conception rate (all P<0.01) and total number of spermatozoa (P<0.05). The peak of growth for spermatozoa concentration, total number of spermatozoa, insemination doses and conception rate was achieved for 800 to 850 g gains. Meat content affected semen volume, number of insemination doses and conception rate (P<0.05). Rearing boars while maintaining daily gains at the 800 to 850 g level and 62.5% to 65% meat content helps AI stations to increase the efficiency and economic profitability, and the number of insemination doses to increase by up to 300 doses/boar within a year. The analyses of growth parameters may help increase the efficiency and economic viability of AI stations.

A retrospective analysis for patient-specific quality assurance of volumetric-modulated arc therapy plans.

PubMed

Li, Guangjun; Wu, Kui; Peng, Guang; Zhang, Yingjie; Bai, Sen

2014-01-01

Volumetric-modulated arc therapy (VMAT) is now widely used clinically, as it is capable of delivering a highly conformal dose distribution in a short time interval. We retrospectively analyzed patient-specific quality assurance (QA) of VMAT and examined the relationships between the planning parameters and the QA results. A total of 118 clinical VMAT cases underwent pretreatment QA. All plans had 3-dimensional diode array measurements, and 69 also had ion chamber measurements. Dose distribution and isocenter point dose were evaluated by comparing the measurements and the treatment planning system (TPS) calculations. In addition, the relationship between QA results and several planning parameters, such as dose level, control points (CPs), monitor units (MUs), average field width, and average leaf travel, were also analyzed. For delivered dose distribution, a gamma analysis passing rate greater than 90% was obtained for all plans and greater than 95% for 100 of 118 plans with the 3%/3-mm criteria. The difference (mean ± standard deviation) between the point doses measured by the ion chamber and those calculated by TPS was 0.9% ± 2.0% for all plans. For all cancer sites, nasopharyngeal carcinoma and gastric cancer have the lowest and highest average passing rates, respectively. From multivariate linear regression analysis, the dose level (p = 0.001) and the average leaf travel (p < 0.001) showed negative correlations with the passing rate, and the average field width (p = 0.003) showed a positive correlation with the passing rate, all indicating a correlation between the passing rate and the plan complexity. No statistically significant correlation was found between MU or CP and the passing rate. Analysis of the results of dosimetric pretreatment measurements as a function of VMAT plan parameters can provide important information to guide the plan parameter setting and optimization in TPS. Copyright © 2014 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

A retrospective analysis for patient-specific quality assurance of volumetric-modulated arc therapy plans

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

Li, Guangjun; Wu, Kui; Peng, Guang

2014-01-01

Volumetric-modulated arc therapy (VMAT) is now widely used clinically, as it is capable of delivering a highly conformal dose distribution in a short time interval. We retrospectively analyzed patient-specific quality assurance (QA) of VMAT and examined the relationships between the planning parameters and the QA results. A total of 118 clinical VMAT cases underwent pretreatment QA. All plans had 3-dimensional diode array measurements, and 69 also had ion chamber measurements. Dose distribution and isocenter point dose were evaluated by comparing the measurements and the treatment planning system (TPS) calculations. In addition, the relationship between QA results and several planning parameters,more » such as dose level, control points (CPs), monitor units (MUs), average field width, and average leaf travel, were also analyzed. For delivered dose distribution, a gamma analysis passing rate greater than 90% was obtained for all plans and greater than 95% for 100 of 118 plans with the 3%/3-mm criteria. The difference (mean ± standard deviation) between the point doses measured by the ion chamber and those calculated by TPS was 0.9% ± 2.0% for all plans. For all cancer sites, nasopharyngeal carcinoma and gastric cancer have the lowest and highest average passing rates, respectively. From multivariate linear regression analysis, the dose level (p = 0.001) and the average leaf travel (p < 0.001) showed negative correlations with the passing rate, and the average field width (p = 0.003) showed a positive correlation with the passing rate, all indicating a correlation between the passing rate and the plan complexity. No statistically significant correlation was found between MU or CP and the passing rate. Analysis of the results of dosimetric pretreatment measurements as a function of VMAT plan parameters can provide important information to guide the plan parameter setting and optimization in TPS.« less

Natural radionuclides in cigarette tobacco from Serbian market and effective dose estimate from smoke inhalation.

PubMed

Janković Mandić, Ljiljana; Đolić, Maja; Marković, Dragana; Todorović, Dragana; Onjia, Antonije; Dragović, Snežana

2016-01-01

The activity concentrations of natural radionuclides ((40)K, (210)Pb, (210)Po, (226)Ra and (228)Ra) in 17 most frequently used cigarette brands in Serbia and corresponding effective doses due to smoke inhalation are presented. The mean annual effective doses for (210)Pb and (210)Po were estimated to be 47.3 and 724 µSv y(-1) for (210)Pb and (210)Po, respectively. Serbia currently has the highest smoking rate in the world. The results of this study indicate the high contribution of the annual effective dose due to smoke inhalation to the total inhalation dose from natural radionuclides. The more effective implementation of actions for reducing smoking prevalence in Serbia is highly needed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radiological risk assessment of Capstone depleted uranium aerosols.

PubMed

Hahn, Fletcher F; Roszell, Laurie E; Daxon, Eric G; Guilmette, Raymond A; Parkhurst, Mary Ann

2009-03-01

Assessment of the health risk from exposure to aerosols of depleted uranium (DU) is an important outcome of the Capstone aerosol studies that established exposure ranges to personnel in armored combat vehicles perforated by DU munitions. Although the radiation exposure from DU is low, there is concern that DU deposited in the body may increase cancer rates. Radiation doses to various organs of the body resulting from the inhalation of DU aerosols measured in the Capstone studies were calculated using International Commission on Radiological Protection (ICRP) models. Organs and tissues with the highest calculated committed equivalent 50-y doses were lung and extrathoracic tissues (nose and nasal passages, pharynx, larynx, mouth, and thoracic lymph nodes). Doses to the bone surface and kidney were about 5 to 10% of the doses to the extrathoracic tissues. Organ-specific risks were estimated using ICRP and U.S. Environmental Protection Agency (EPA) methodologies. Risks for crewmembers and first responders were determined for selected scenarios based on the time interval of exposure and for vehicle and armor type. The lung was the organ with the highest cancer mortality risk, accounting for about 97% of the risks summed from all organs. The highest mean lifetime risk for lung cancer for the scenario with the longest exposure time interval (2 h) was 0.42%. This risk is low compared with the natural or background risk of 7.35%. These risks can be significantly reduced by using an existing ventilation system (if operable) and by reducing personnel time in the vehicle immediately after perforation.

Natural gamma-radiation in the Aeolian volcanic arc.

PubMed

Chiozzi, P; Pasquale, V; Verdoya, M; Minato, S

2001-11-01

Pulse-height distributions of gamma-rays, obtained with a field NaI(Tl) scintillation spectrometer in numerous sites of the Lipari and Vulcano islands (Aeolian volcanic arc, Italy), were measured to determine the U, Th and K concentrations of the bedrock and the relative values of the air absorbed dose rate. U is spatially related to both Th and K and the Th/U ratio is on average 3.1-3.5. The magmatic evolution is reflected by the concentration of the three radioelements, as they are more abundant within the more felsic units of the volcanic series. The higher values of U (15.7-20.0 ppm) coincide with higher Th (48.3-65.9 ppm) and K (4.9-6.1%) concentrations associated with rhyolitic rocks of the third cycle (< 50 ky). The air absorbed dose rate varies from 20 to 470 nGy h(-1). The highest values (> 350 nGy h(-1)) are observed on outcrops of rhyolitic obsidian lava flows. The cosmic-ray contribution is also evaluated to estimate the total background radiation dose rate.

Acute and Short-Term Inhalation Toxicity Study of FT Fuel

DTIC Science & Technology

2011-02-01

Nasopharyngeal duct goblet cell hypertrophy/hyperplasia is evident in both sexes of rats exposed to the two highest doses of jet fuel. 47 Distribution A...findings in lung, nose and liver and, in male rats, kidneys. Inflammatory foci were evident in the lungs of both sexes of rat exposed to the two...highest doses of jet fuel. Olfactory epithelial degeneration was evident in both sexes of rats exposed to the two highest doses of jet fuel. An

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Resistance to plague among black-tailed prairie dog populations.

PubMed

Rocke, Tonie E; Williamson, Judy; Cobble, Kacy R; Busch, Joseph D; Antolin, Michael F; Wagner, David M

2012-02-01

In some rodent species frequently exposed to plague outbreaks caused by Yersinia pestis, resistance to the disease has evolved as a population trait. As a first step in determining if plague resistance has developed in black-tailed prairie dogs (Cynomys ludovicianus), animals captured from colonies in a plague-free region (South Dakota) and two plague-endemic regions (Colorado and Texas) were challenged with Y. pestis at one of three doses (2.5, 250, or 2500 mouse LD50s). South Dakota prairie dogs were far more susceptible to plague than Colorado and Texas prairie dogs (p<0.001), with a mortality rate of nearly 100% over all doses. Colorado and Texas prairie dogs were quite similar in their response, with overall survival rates of 50% and 60%, respectively. Prairie dogs from these states were heterogeneous in their response, with some animals dying at the lowest dose (37% and 20%, respectively) and some surviving even at the highest dose (29% and 40%, respectively). Microsatellite analysis revealed that all three groups were distinct genetically, but further studies are needed to establish a genetic basis for the observed differences in plague resistance.

Resistance to plague among black-tailed prairie dog populations

USGS Publications Warehouse

Rocke, Tonie E.; Williamson, Judy; Cobble, Kacy R.; Busch, Joseph D.; Antolin, Michael F.; Wagner, David M.

2012-01-01

In some rodent species frequently exposed to plague outbreaks caused by Yersinia pestis, resistance to the disease has evolved as a population trait. As a first step in determining if plague resistance has developed in black-tailed prairie dogs (Cynomys ludovicianus), animals captured from colonies in a plague-free region (South Dakota) and two plague-endemic regions (Colorado and Texas) were challenged with Y. pestis at one of three doses (2.5, 250, or 2500 mouse LD50s). South Dakota prairie dogs were far more susceptible to plague than Colorado and Texas prairie dogs (p<0.001), with a mortality rate of nearly 100% over all doses. Colorado and Texas prairie dogs were quite similar in their response, with overall survival rates of 50% and 60%, respectively. Prairie dogs from these states were heterogenous in their response, with some animals dying at the lowest dose (37% and 20%, respectively) and some surviving even at the highest dose (29% and 40%, respectively). Microsatellite analysis revealed that all three groups were distinct genetically, but further studies are needed to establish a genetic basis for the observed differences in plague resistance.

Environmental radioactivity in the UK: the airborne geophysical view of dose rate estimates.

PubMed

Beamish, David

2014-12-01

This study considers UK airborne gamma-ray data obtained through a series of high spatial resolution, low altitude surveys over the past decade. The ground concentrations of the naturally occurring radionuclides Potassium, Thorium and Uranium are converted to air absorbed dose rates and these are used to assess terrestrial exposure levels from both natural and technologically enhanced sources. The high resolution airborne information is also assessed alongside existing knowledge from soil sampling and ground-based measurements of exposure levels. The surveys have sampled an extensive number of the UK lithological bedrock formations and the statistical information provides examples of low dose rate lithologies (the formations that characterise much of southern England) to the highest sustained values associated with granitic terrains. The maximum dose rates (e.g. >300 nGy h(-1)) encountered across the sampled granitic terrains are found to vary by a factor of 2. Excluding granitic terrains, the most spatially extensive dose rates (>50 nGy h(-1)) are found in association with the Mercia Mudstone Group (Triassic argillaceous mudstones) of eastern England. Geological associations between high dose rate and high radon values are also noted. Recent studies of the datasets have revealed the extent of source rock (i.e. bedrock) flux attenuation by soil moisture in conjunction with the density and porosity of the temperate latitude soils found in the UK. The presence or absence of soil cover (and associated presence or absence of attenuation) appears to account for a range of localised variations in the exposure levels encountered. The hypothesis is supported by a study of an extensive combined data set of dose rates obtained from soil sampling and by airborne geophysical survey. With no attenuation factors applied, except those intrinsic to the airborne estimates, a bias to high values of between 10 and 15 nGy h(-1) is observed in the soil data. A wide range of technologically enhanced, localised contributions to dose rate values are also apparent in the data sets. Two detailed examples are provided that reveal the detectability of site-scale environmental impacts due to former industrial activities and the high dose values (>500 nGy h(-1)) that are associated with former, small-scale Uranium mining operations. Copyright © 2014. Published by Elsevier Ltd.

The biological impacts of ingested radioactive materials on the pale grass blue butterfly

NASA Astrophysics Data System (ADS)

Nohara, Chiyo; Hiyama, Atsuki; Taira, Wataru; Tanahara, Akira; Otaki, Joji M.

2014-05-01

A massive amount of radioactive materials has been released into the environment by the Fukushima Dai-ichi Nuclear Power Plant accident, but its biological impacts have rarely been examined. Here, we have quantitatively evaluated the relationship between the dose of ingested radioactive cesium and mortality and abnormality rates using the pale grass blue butterfly, Zizeeria maha. When larvae from Okinawa, which is likely the least polluted locality in Japan, were fed leaves collected from polluted localities, mortality and abnormality rates increased sharply at low doses in response to the ingested cesium dose. This dose-response relationship was best fitted by power function models, which indicated that the half lethal and abnormal doses were 1.9 and 0.76 Bq per larva, corresponding to 54,000 and 22,000 Bq per kilogram body weight, respectively. Both the retention of radioactive cesium in a pupa relative to the ingested dose throughout the larval stage and the accumulation of radioactive cesium in a pupa relative to the activity concentration in a diet were highest at the lowest level of cesium ingested. We conclude that the risk of ingesting a polluted diet is realistic, at least for this butterfly, and likely for certain other organisms living in the polluted area.

The biological impacts of ingested radioactive materials on the pale grass blue butterfly.

PubMed

Nohara, Chiyo; Hiyama, Atsuki; Taira, Wataru; Tanahara, Akira; Otaki, Joji M

2014-05-15

A massive amount of radioactive materials has been released into the environment by the Fukushima Dai-ichi Nuclear Power Plant accident, but its biological impacts have rarely been examined. Here, we have quantitatively evaluated the relationship between the dose of ingested radioactive cesium and mortality and abnormality rates using the pale grass blue butterfly, Zizeeria maha. When larvae from Okinawa, which is likely the least polluted locality in Japan, were fed leaves collected from polluted localities, mortality and abnormality rates increased sharply at low doses in response to the ingested cesium dose. This dose-response relationship was best fitted by power function models, which indicated that the half lethal and abnormal doses were 1.9 and 0.76 Bq per larva, corresponding to 54,000 and 22,000 Bq per kilogram body weight, respectively. Both the retention of radioactive cesium in a pupa relative to the ingested dose throughout the larval stage and the accumulation of radioactive cesium in a pupa relative to the activity concentration in a diet were highest at the lowest level of cesium ingested. We conclude that the risk of ingesting a polluted diet is realistic, at least for this butterfly, and likely for certain other organisms living in the polluted area.

Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

NASA Technical Reports Server (NTRS)

Kumagai, Kazuhiro; Reid, Ian A.

1994-01-01

We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

A new biostimulation approach based on the concept of remaining P for soil bioremediation.

PubMed

Júlio, Aline Daniela Lopes; Fernandes, Rita de Cássia Rocha; Costa, Maurício Dutra; Neves, Júlio César Lima; Rodrigues, Edmo Montes; Tótola, Marcos Rogério

2018-02-01

C:N:P ratio is generally adopted to estimate the amount of nitrogen and phosphorus to be added to soils to accelerate biodegradation of organic contaminants. However, differences in P fixation among soils lead to varying amounts of available P when a specific dose of the element is applied to different soils. Thus, the application of fertilizers to achieve a previously established C:P ratio leads to biodegradation rates that can be lower than the theoretical maximum. In this study, we developed an equation to estimate the dose of P required to maximize organic contaminant biodegradation in soils as a function of remaining P (P-rem), using diesel as a model contaminant. The soils were contaminated with diesel and received six doses of P. CO 2 emission was used to estimate biodegradation of hydrocarbons. Biodegradation increased with P doses. The P level that provided the highest hydrocarbon biodegradation rate showed linear and negative correlation with P-rem. The result shows that the requirement for P decreases as the P-rem of the soil increases (or the P-fixing capacity decreases). The dose of P recommended to maximize hydrocarbon biodegradation rate in soil can be estimated by the formula P (mg/dm 3 ) = 436.5-5.39 × P-rem (mg/L). Copyright © 2017 Elsevier Ltd. All rights reserved.

A Novel ATM/TP53/p21-Mediated Checkpoint Only Activated by Chronic γ-Irradiation

PubMed Central

Sasatani, Megumi; Iizuka, Daisuke; Masuda, Yuji; Inaba, Toshiya; Suzuki, Keiji; Ootsuyama, Akira; Umata, Toshiyuki; Kamiya, Kenji; Suzuki, Fumio

2014-01-01

Different levels or types of DNA damage activate distinct signaling pathways that elicit various cellular responses, including cell-cycle arrest, DNA repair, senescence, and apoptosis. Whereas a range of DNA-damage responses have been characterized, mechanisms underlying subsequent cell-fate decision remain elusive. Here we exposed cultured cells and mice to different doses and dose rates of γ-irradiation, which revealed cell-type-specific sensitivities to chronic, but not acute, γ-irradiation. Among tested cell types, human fibroblasts were associated with the highest levels of growth inhibition in response to chronic γ-irradiation. In this context, fibroblasts exhibited a reversible G1 cell-cycle arrest or an irreversible senescence-like growth arrest, depending on the irradiation dose rate or the rate of DNA damage. Remarkably, when the same dose of γ-irradiation was delivered chronically or acutely, chronic delivery induced considerably more cellular senescence. A similar effect was observed with primary cells isolated from irradiated mice. We demonstrate a critical role for the ataxia telangiectasia mutated (ATM)/tumor protein p53 (TP53)/p21 pathway in regulating DNA-damage-associated cell fate. Indeed, blocking the ATM/TP53/p21 pathway deregulated DNA damage responses, leading to micronucleus formation in chronically irradiated cells. Together these results provide insights into the mechanisms governing cell-fate determination in response to different rates of DNA damage. PMID:25093836

Effects of acute buspirone administration on inhibitory control and sexual discounting in cocaine users.

PubMed

Strickland, Justin C; Bolin, B Levi; Romanelli, Michael R; Rush, Craig R; Stoops, William W

2017-01-01

Cocaine users display deficits in inhibitory control and make impulsive choices that may increase risky behavior. Buspirone is an anxiolytic that activates dopaminergic and serotonergic systems and improves impulsive choice (i.e., reduces sexual risk-taking intent) in cocaine users when administered chronically. We evaluated the effects of acutely administered buspirone on inhibitory control and impulsive choice. Eleven subjects with a recent history of cocaine use completed this within-subject, placebo-controlled study. Subjects performed two cued go/no-go and a sexual risk delay-discounting task following oral administration of buspirone (10 and 30 mg), triazolam (0.375 mg; positive control), and placebo (negative control). Physiological and psychomotor performance and subject-rated data were also collected. Buspirone failed to change inhibitory control or impulsive choice; however, slower reaction times were observed at the highest dose tested. Buspirone did not produce subject-rated drug effects but dose-dependently decreased diastolic blood pressure. Triazolam impaired psychomotor performance and increased ratings of positive subject-rated effects (e.g., Like Drug). These findings indicate that acutely administered buspirone has little impact on behavioral measures of inhibitory control and impulsive sexual decision-making. Considering previous findings with chronic dosing, these findings highlight that the behavioral effects of buspirone differ as a function of dosing conditions. Copyright © 2017 John Wiley & Sons, Ltd.

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; McCann, Una; Jesse, Robert

2011-12-01

This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

Psychopharmacology of theobromine in healthy volunteers.

PubMed

Baggott, Matthew J; Childs, Emma; Hart, Amy B; de Bruin, Eveline; Palmer, Abraham A; Wilkinson, Joy E; de Wit, Harriet

2013-07-01

Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.

Psychopharmacology of theobromine in healthy volunteers

PubMed Central

Baggott, Matthew J.; Childs, Emma; Hart, Amy B.; de Bruin, Eveline; Palmer, Abraham A.; Wilkinson, Joy E.; de Wit, Harriet

2013-01-01

Background Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, currently evidence for this is limited. Objectives We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Results Caffeine had the expected effects on mood including feelings of alertness, and cardiovascular parameters. Theobromine responses differed according to dose: it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses we also examined individual differences in the drugs' effects in relation to genes related to their target receptors, but few associations were detected. Conclusions This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes effects become negative. PMID:23420115

Dosimetry around metallic ports in tissue expanders in patients receiving postmastectomy radiation therapy: an ex vivo evaluation.

PubMed

Moni, Janaki; Graves-Ditman, Maria; Cederna, Paul; Griffith, Kent; Krueger, Editha A; Fraass, Benedick A; Pierce, Lori J

2004-01-01

Postmastectomy breast reconstruction can be accomplished utilizing tissue expanders and implants. However, in patients who require postoperative radiotherapy, the complication rate with tissue expander/implant reconstruction can exceed 50%. One potential cause of this high complication rate may be the metallic port in the tissue expander producing altered dosimetry in the region of the metallic device. The purpose of this study was to quantify the radiation dose distribution in the vicinity of the metallic port and determine its potential contribution to this extremely high complication rate. The absolute dosimetric effect of the tissue expander's metallic port was quantified using film and thermoluminescent dosimetry (TLD) studies with a single beam incident on a metallic port extracted from an expander. TLD measurements were performed at 11 reproducible positions on an intact expander irradiated with tangential fields. A computed tomography (CT)-based treatment plan without inhomogeneity corrections was used to derive expected doses for all TLD positions. Multiple irradiation experiments were performed for all TLD data. Confidence intervals for the dose at TLD sites with the metallic port in place were compared to the expected dose at the site without the metallic port. Film studies did not reveal a significant component of scatter around the metallic port. TLD studies of the extracted metallic port revealed highest doses within the casing of the metallic port and no consistent increased dose at the surface of the expander. No excess dose due to the metallic port in the expander was noted with the phantom TLD data. Based upon these results, it does not appear that the metallic port in tissue expanders significantly contributes to the high complication rate experienced in patients undergoing tissue expander breast reconstruction and receiving radiation therapy. Strategies designed to reduce the breast reconstruction complication rate in this clinical setting will need to focus on factors other than adjusting the dosimetry around the tissue expander metallic port.

Outdoor Exposure to Solar Ultraviolet Radiation and Legislation in Brazil.

PubMed

Silva, Abel A

2016-06-01

The total ozone column of 265 ± 11 Dobson Units in the tropical-equatorial zones and 283 ± 16 Dobson Units in the subtropics of Brazil are among the lowest on Earth, and as a result, the prevalence of skin cancer due to solar ultraviolet radiation is among the highest. Daily erythemal doses in Brazil can be over 7,500 J m. Erythemal dose rates on cloudless days of winter and summer are typically about 0.147 W m and 0.332 W m, respectively. However, radiation enhancement events yielded by clouds have been reported with erythemal dose rates of 0.486 W m. Daily doses of the diffuse component of erythemal radiation have been determined with values of 5,053 J m and diffuse erythemal dose rates of 0.312 W m. Unfortunately, Brazilians still behave in ways that lead to overexposure to the sun. The annual personal ultraviolet radiation ambient dose among Brazilian youths can be about 5.3%. Skin cancer in Brazil is prevalent, with annual rates of 31.6% (non-melanoma) and 1.0% (melanoma). Governmental and non-governmental initiatives have been taken to increase public awareness of photoprotection behaviors. Resolution #56 by the Agência Nacional de Vigilância Sanitária has banned tanning devices in Brazil. In addition, Projects of Law (PL), like PL 3730/2004, propose that the Sistema Único de Saúde should distribute sunscreen to members of the public, while PL 4027/2012 proposes that employers should provide outdoor workers with sunscreen during professional outdoor activities. Similar laws have already been passed in some municipalities. These are presented and discussed in this study.

Single toxin dose-response models revisited

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

Demidenko, Eugene, E-mail: eugened@dartmouth.edu

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the fourmore » models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.« less

Radiological Risk Assessment of Capstone Depleted Uranium Aerosols

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

Hahn, Fletcher; Roszell, Laurie E.; Daxon, Eric G.

2009-02-26

Assessment of the health risk from exposure to aerosols of depleted uranium (DU) is an important outcome of the Capstone aerosol studies that established exposure ranges to personnel in armored combat vehicles perforated by DU munitions. Although the radiation exposure from DU is low, there is concern that DU deposited in the body may increase cancer rates. Radiation doses to various organs of the body resulting from the inhalation of DU aerosols measured in the Capstone studies were calculated using International Commission on Radiological Protection (ICRP) models. Organs and tissues with the highest calculated committed equivalent 50-yr doses were lungmore » and extrathoracic tissues (nose and nasal passages, pharynx, larynx, mouth and thoracic lymph nodes). Doses to the bone surface and kidney were about 5 to 10% of the doses to the extrathoracic tissues. The methodologies of the ICRP International Steering Committee on Radiation Standards (ISCORS) were used for determining the whole body cancer risk. Organ-specific risks were estimated using ICRP and U.S. Environmental Protection Agency (EPA) methodologies. Risks for crewmembers and first responders were determined for selected scenarios based on the time interval of exposure and for vehicle and armor type. The lung was the organ with the highest cancer mortality risk, accounting for about 97% of the risks summed from all organs. The highest mean lifetime risk for lung cancer for the scenario with the longest exposure time interval (2 h) was 0.42%. This risk is low compared with the natural or background risk of 7.35%. These risks can be significantly reduced by using an existing ventilation system (if operable) and by reducing personnel time in the vehicle immediately after perforation.« less

Recent resurgence of mumps in the United States.

PubMed

Dayan, Gustavo H; Quinlisk, M Patricia; Parker, Amy A; Barskey, Albert E; Harris, Meghan L; Schwartz, Jennifer M Hill; Hunt, Kae; Finley, Carol G; Leschinsky, Dennis P; O'Keefe, Anne L; Clayton, Joshua; Kightlinger, Lon K; Dietle, Eden G; Berg, Jeffrey; Kenyon, Cynthia L; Goldstein, Susan T; Stokley, Shannon K; Redd, Susan B; Rota, Paul A; Rota, Jennifer; Bi, Daoling; Roush, Sandra W; Bridges, Carolyn B; Santibanez, Tammy A; Parashar, Umesh; Bellini, William J; Seward, Jane F

2008-04-10

The widespread use of a second dose of mumps vaccine among U.S. schoolchildren beginning in 1990 was followed by historically low reports of mumps cases. A 2010 elimination goal was established, but in 2006 the largest mumps outbreak in two decades occurred in the United States. We examined national data on mumps cases reported during 2006, detailed case data from the most highly affected states, and vaccination-coverage data from three nationwide surveys. A total of 6584 cases of mumps were reported in 2006, with 76% occurring between March and May. There were 85 hospitalizations, but no deaths were reported; 85% of patients lived in eight contiguous midwestern states. The national incidence of mumps was 2.2 per 100,000, with the highest incidence among persons 18 to 24 years of age (an incidence 3.7 times that of all other age groups combined). In a subgroup analysis, 83% of these patients reported current college attendance. Among patients in eight highly affected states with known vaccination status, 63% overall and 84% between the ages of 18 and 24 years had received two doses of mumps vaccine. For the 12 years preceding the outbreak, national coverage of one-dose mumps vaccination among preschoolers was 89% or more nationwide and 86% or more in highly affected states. In 2006, the national two-dose coverage among adolescents was 87%, the highest in U.S. history. Despite a high coverage rate with two doses of mumps-containing vaccine, a large mumps outbreak occurred, characterized by two-dose vaccine failure, particularly among midwestern college-age adults who probably received the second dose as schoolchildren. A more effective mumps vaccine or changes in vaccine policy may be needed to avert future outbreaks and achieve the elimination of mumps. Copyright 2008 Massachusetts Medical Society.

D-T Neutron Skyshine Experiments at JAERI/FNS

NASA Astrophysics Data System (ADS)

Nishitani, Takeo; Ochiai, Kentaro; Yoshida, Shigeo; Tanaka, Ryohei; Wakisaka, Masashi; Nakao, Makoto; Sato, Satoshi; Yamauchi, Michinori; Hori, Jun-Ichi; Takahashi, Akito; Kaneko, Jun-Ichi; Sawamura, Teruko

The D-T neutron skyshine experiments have been carried out at the Fusion Neutronics Source (FNS) of JAERI with the neutron yield of ˜1.7×1011n/s. The concrete thickness of the roof and the wall of a FNS target room are 1.15 and 2 m, respectively. The FNS skyshine port with a size of 0.9 × 0.9 m2 was open during the experimental period.The radiation dose rate outside the target room was measured as far as about 550 m away from the D-T target point with a spherical rem-counter. The highest neutron dose was about 0.5 μSv/hr at a distance of 30 m from the D-T target point and the dose rate was attenuated to 0.002 μSv/hr at a distance of 550 m. The measured neutron dose distribution was analyzed with Monte Carlo code MCNP-4B and a simple line source model. The MCNP calculation overestimates the neutron dose in the distance range larger than 250 m. The neutron spectra were evaluated with a 3He detector with different thickness of polyethylene neutron moderators. Secondary gamma-rays were measured with high purity Ge detectors and NaI scintillation detectors.

Reduced anticoagulation variability in patients on warfarin monitored with Fiix-prothrombin time associates with reduced thromboembolism: The Fiix-trial.

PubMed

Oskarsdóttir, Alma Rut; Gudmundsdottir, Brynja R; Indridason, Olafur S; Lund, Sigrun H; Arnar, David O; Bjornsson, Einar S; Magnusson, Magnus K; Jensdottir, Hulda M; Vidarsson, Brynjar; Francis, Charles W; Onundarson, Pall T

2017-05-01

Fiix-prothrombin time (Fiix-PT) differs from traditional PT in being affected by reduced factor (F) II or FX only. In the randomized controlled Fiix-trial, patients on warfarin monitored with Fiix-PT (Fiix-warfarin patients) had fewer thromboembolisms (TE), similar major bleeding (MB) and more stable anticoagulation than patients monitored with PT (PT-warfarin patients). In the current Fiix-trial report we analyzed how reduced anticoagulation variability during Fiix-PT monitoring was reflected in patients with TE or bleeding. Data from 1143 randomized patients was used. We analyzed the groups for anticoagulation intensity (time within target range; TTR), international normalized ratio (INR) variability (variance growth rate B 1 ; VGR) and dose adjustment frequency. We assessed how these parameters associated with clinically relevant vascular events (CRVE), ie TE or MB or clinically relevant non-MB. TTR was highest in Fiix-warfarin patients without CRVE (median 82%;IQR 72-91) and lowest in PT-warfarin patients with TE (62%;56-81). VGR was lowest in Fiix-warfarin patients without CRVE (median VGR B 1 0.17; 95% CI 0.08-0.38) and with TE (0.20;0.07-0.26) and highest in PT-warfarin patients with TE (0.50;0.27-0.90) or MB (0.59;0.07-1.36). The mean annual dose adjustment frequency was lowest in Fiix-warfarin patients with TE (mean 5.4;95% CI 3.9-7.3) and without CRVE (mean 6.0; 5.8-6.2) and highest in PT-warfarin patients with TE (14.2;12.2-16.3). Frequent dose changes predicted MB in both study arms. Compared to patients monitored with PT, high anticoagulation stability in Fiix-warfarin patients coincided with their low TE rate. Those with bleeding had high variability irrespective of monitoring method. Thus, although further improvements are needed to reduce bleeding, stabilization of anticoagulation by Fiix-PT monitoring associates with reduced TE.

Systematic review of reporting rates of adverse events following immunization: an international comparison of post-marketing surveillance programs with reference to China.

PubMed

Guo, Biao; Page, Andrew; Wang, Huaqing; Taylor, Richard; McIntyre, Peter

2013-01-11

China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse. To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally. Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages. Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3-37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria-tetanus-pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3-181.1/100,000 doses for DTwP; range 3.5-92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world. Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Modelling the external radiation exposure from the Chernobyl fallout using data from the Swedish municipality measurement system.

PubMed

Jönsson, Mattias; Tondel, Martin; Isaksson, Mats; Finck, Robert; Wålinder, Robert; Mamour, Afrah; Rääf, Christopher

2017-11-01

In connection with the Chernobyl fallout and the subsequent deposition of radionuclides in Sweden, Swedish municipalities launched a measurement program to monitor the external radiation exposure. This program encompasses measurements of the ambient dose equivalent rate 1 m above ground at selected locations, and repeats those measurements at the same locations at 7-month intervals. Measurement data compiled from the seven locations with the highest deposition were combined with data from aerial surveys since May 1986 of ground deposition of 137 Cs, high-resolution gamma spectrometry performed at four locations in May 1986, and measurements from fixed continuous air gamma rate monitoring stations from 28 April to 15 May 1986. Based on these datasets, a model of the time pattern of the external dose rate in terms of ambient dose equivalent rate from the Chernobyl fallout was developed. The decrease in the ambient dose equivalent rate could, on average, be described by a four-component exponential decay function with effective half-times of 6.8 ± 0.3 d, 104 ± 26 d, 1.0 ± 0.02 y and 5.5 ± 0.09 y, respectively. The predominant contributions to the external dose rate in the first month were from short-lived fission products superseded by 134 Cs and then 137 Cs. Integrated over 70 y and using extrapolation of the curve fits, our model predicts that 137 Cs contributes about 60% and 134 Cs contributes about 30% of the external effective dose at these seven locations. The projected time-integrated 70 y external effective dose to an unshielded person from all nuclides per unit total activity deposition of 137 Cs is estimated to be 0.29 ± 0.0.08 mSv/(kBq m -2 ). These results are in agreement with those found in Chernobyl contaminated Russian forest areas, and emphasize the usefulness of maintaining a long-term and regular measurement program in contaminated areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psilocybin occasioned mystical-type experiences: Immediate and persisting dose-related effects

PubMed Central

Griffiths, R. R.; Johnson, M.W.; Richards, W. A.; Richards, B.D.; McCann, U.; Jesse, R.

2012-01-01

Rationale This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Objectives This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Methods Participants were 18 adults (17 hallucinogen-naïve). Five 8-hour sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (9 participants each). Placebo was scheduled quasi-randomly. During sessions volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Results Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Conclusions Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood and behavior. Implications for therapeutic trials are discussed. PMID:21674151

Cosmic radiation exposure of biological test systems during the EXPOSE-E mission.

PubMed

Berger, Thomas; Hajek, Michael; Bilski, Pawel; Körner, Christine; Vanhavere, Filip; Reitz, Günther

2012-05-01

In the frame of the EXPOSE-E mission on the Columbus external payload facility EuTEF on board the International Space Station, passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located either as stacks next to biological specimens to determine the depth dose distribution or beneath the sample carriers to determine the dose levels for maximum shielding. The maximum mission dose measured in the upper layer of the depth dose part of the experiment amounted to 238±10 mGy, which relates to an average dose rate of 408±16 μGy/d. In these stacks of about 8 mm height, the dose decreased by 5-12% with depth. The maximum dose measured beneath the sample carriers was 215±16 mGy, which amounts to an average dose rate of 368±27 μGy/d. These values are close to those assessed for the interior of the Columbus module and demonstrate the high shielding of the biological experiments within the EXPOSE-E facility. Besides the shielding by the EXPOSE-E hardware itself, additional shielding was experienced by the external structures adjacent to EXPOSE-E, such as EuTEF and Columbus. This led to a dose gradient over the entire exposure area, from 215±16 mGy for the lowest to 121±6 mGy for maximum shielding. Hence, the doses perceived by the biological samples inside EXPOSE-E varied by 70% (from lowest to highest dose). As a consequence of the high shielding, the biological samples were predominantly exposed to galactic cosmic heavy ions, while electrons and a significant fraction of protons of the radiation belts and solar wind did not reach the samples.

Surveillance of adverse events following vaccination in the French armed forces, 2011-2012.

PubMed

Mayet, A; Duron, S; Meynard, J-B; Koeck, J-L; Deparis, X; Migliani, R

2015-06-01

French military personnel are subject to a compulsory vaccination schedule. The aim of this study was to present the results of surveillance of vaccine adverse events (VAEs) reported from 2011 to 2012 in the French armed forces. VAEs were surveyed among all French armed forces from 2011 to 2012 by the epidemiological departments of the military health service. For each case, a notification form providing patient and clinical information was provided. Case definitions were derived from the French drug safety guidelines. Three types of VAE were considered: non-serious, serious and unexpected. Incidence rates were calculated by relating VAEs to the number of vaccine doses delivered. In total, 161 VAE cases were reported. The overall VAE reporting rate was 24.6 VAEs per 100,000 doses, and the serious VAE rate was 1.3 per 100,000 doses (nine cases). The serious VAEs included two cases of Guillain-Barré syndrome, one case of optic neuritis, one case of a meningeal-like syndrome, one case of rheumatoid purpura, one case of acute asthma and three cases of fainting. The highest rates of VAE were observed with the Bacille Calmette-Guérin vaccine (BCG) (482.3 per 100,000 doses), inactivated diphtheria-tetanus-poliovirus with acellular pertussis vaccine (dTap-IPV) (106.1 per 100,000 doses) and meningococcal quadrivalent glycoconjugate vaccine (MenACWY-CRM) (39.3 per 100,000 doses). The global rates of VAE observed in 2011 and 2012 confirm the increase that has been observed since 2009 in the French armed forces, which could reflect improved practitioner awareness about VAEs and the use of certain vaccines added to the vaccination schedule recently (dTap-IPV in 2008 and MenACWY-CRM in 2010). VAEs appear to be relatively rare, particularly serious VAEs, which indicates acceptable tolerance of vaccines. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential

PubMed Central

Reissig, Chad J.; Harrison, Joseph A.; Carter, Lawrence P.; Griffiths, Roland R.

2014-01-01

Rationale Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. Objectives This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Methods Placebo, inhaled alprazolam (0.5, 1, 2 mg), and oral alprazolam (1, 2, 4 mg) were administered under double-blind, double-dummy conditions using a cross-over design in 14 healthy participants with histories of drug abuse. Participant and observer ratings, and behavioral and cognitive performance measures were assessed repeatedly during 9 hour sessions. Results Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 minutes after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., “drug liking”) were similar across the two routes. On other measures (e.g., sedation and performance) the routes were equipotent. Conclusions The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low. PMID:25199955

Inhaled vs. oral alprazolam: subjective, behavioral and cognitive effects, and modestly increased abuse potential.

PubMed

Reissig, Chad J; Harrison, Joseph A; Carter, Lawrence P; Griffiths, Roland R

2015-03-01

Infrahuman and human studies suggest that a determinant of the abuse potential of a drug is rate of onset of subjective effects. This study sought to determine if the rate of onset of subjective effects and abuse potential of alprazolam would be increased when administered via inhalation vs. the oral route. Placebo, inhaled alprazolam (0.5, 1, and 2 mg), and oral alprazolam (1, 2, and 4 mg) were administered under double-blind, double-dummy conditions using a crossover design in 14 healthy participants with histories of drug abuse. Participant and observer ratings and behavioral and cognitive performance measures were assessed repeatedly during 9-h sessions. Both routes of administration produced orderly dose and time-related effects, with higher doses producing greater and longer-lasting effects. Onset of subjective effects following inhaled alprazolam was very rapid (e.g., 2 vs. 49 min after 2 mg inhaled vs. oral). On measures of abuse potential (e.g., liking and good effects), inhaled alprazolam was more potent, as evidenced by a leftward shift in the dose-response curve. Despite the potency difference, at the highest doses, peak ratings of subjective effects related to abuse potential (e.g., "drug liking") were similar across the two routes. On other measures (e.g., sedation and performance), the routes were equipotent. The inhaled route of administration modestly increased the abuse potential of alprazolam despite significantly increasing its rate of onset. If marketed, the reduced availability and increased cost of inhaled alprazolam may render the societal risk of increased abuse to be low.

Spatial interpolation of gamma dose in radioactive waste storage facility

NASA Astrophysics Data System (ADS)

Harun, Nazran; Fathi Sujan, Muhammad; Zaidi Ibrahim, Mohd

2018-01-01

External radiation measurement for a radioactive waste storage facility in Malaysian Nuclear Agency is a part of Class G License requirement under Atomic Licensing Energy Board (AELB). The objectives of this paper are to obtain the distribution of radiation dose, create dose database and generate dose map in the storage facility. The radiation dose measurement is important to fulfil the radiation protection requirement to ensure the safety of the workers. There are 118 sampling points that had been recorded in the storage facility. The highest and lowest reading for external radiation recorded is 651 microSv/hr and 0.648 microSv/hour respectively. The calculated annual dose shows the highest and lowest reading is 1302 mSv/year and 1.3 mSv/year while the highest and lowest effective dose reading is 260.4 mSv/year and 0.26 mSv/year. The result shows that the ALARA concept along time, distance and shield principles shall be adopted to ensure the dose for the workers is kept below the dose limit regulated by AELB which is 20 mSv/year for radiation workers. This study is important for the improvement of planning and the development of shielding design for the facility.

Effect of transfusional iron intake on response to chelation therapy in beta-thalassemia major.

PubMed

Cohen, Alan R; Glimm, Ekkehard; Porter, John B

2008-01-15

The success of chelation therapy in controlling iron overload in patients with thalassemia major is highly variable and may partly depend on the rate of transfusional iron loading. Using data from the 1-year phase III study of deferasirox, including volumes of transfused red blood cells and changes in liver iron concentration (LIC) in 541 patients, the effect of iron loading on achieving neutral or negative iron balance was assessed in patients receiving different doses of deferasirox and the comparator deferoxamine. After dose adjustment, reductions in LIC after 1 year of deferasirox or deferoxamine therapy correlated with transfusional iron intake. At a deferasirox dose of 20 mg/kg per day, neutral or negative iron balance was achieved in 46% and 75% of patients with the highest and lowest transfusional iron intake, respectively; 30 mg/kg per day produced successful control of iron stores in 96% of patients with a low rate of transfusional iron intake. Splenectomized patients had lower transfusional iron intake and greater reductions in iron stores than patients with intact spleens. Transfusional iron intake should be monitored on an ongoing basis in thalassemia major patients, and the rate of transfusional iron loading should be considered when choosing the appropriate dose of an iron-chelating agent. This study is registered at http://clinicaltrials.gov as NCT00061750.

Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine.

PubMed

Hendry, Alexandra J; Dey, Aditi; Beard, Frank H; Khandaker, Gulam; Hill, Richard; Macartney, Kristine K

2016-12-24

In recent years there has been a global shortage of bacille Calmette-Guérin (BCG) vaccine and, from September 2012, unregistered vaccines have needed to be used in Australia (a Danish product initially until the end of 2015, and a Polish product used in some jurisdictions from early 2016). We examined rates and types of adverse events following immunisation (AEFI) with BCG vaccine reported to the Therapeutic Goods Administration between 2009 and 2014 in children aged less than 7 years. Reporting rates of AEFI with BCG vaccine increased from 87 per 100,000 doses (registered Sanofi Pasteur product) in 2009 to 201 per 100,000 doses (unregistered Danish Statens Serum Institute product) in 2014, with Victoria having the highest rate each year. Substantial variation between jurisdictions exists, suggesting differential reporting of BCG vaccine doses administered and/or BCG vaccine-related AEFI. The most commonly reported reactions were abscess (31%), injection site reaction (27%) and lymphadenopathy/lymphadenitis (17%). This study provides baseline data on BCG vaccine safety to inform surveillance. Given the current use of unregistered vaccines in the context of vaccine supply issues, improved recording of both administered BCG vaccine doses and the reporting of BCG vaccine-related AEFI are required to facilitate close monitoring of vaccine safety.

Dose-response relation between physical activity and cognitive function: guangzhou biobank cohort study.

PubMed

Xu, Lin; Jiang, Chao Qiang; Lam, Tai Hing; Zhang, Wei Sen; Thomas, G Neil; Cheng, Kar Keung

2011-11-01

To examine, via cross-sectional analysis, the dose-response association between physical activity and cognitive function in Chinese subjects. A total of 27,651 participants aged 50 to 85 years were recruited from 2003 to 2008. Information on potential confounders, including demographic and anthropometric characteristics, socioeconomic position, lifestyle, and disease history, was collected by standardized interview and procedures. Cognitive function was assessed by the delayed 10-word recall test (DWRT). When the International Physical Activity Questionnaire was used, we found that most of the participants were classified as physically active (53.1%), with 42.4% moderately active and 4.5% physically inactive. Significant dose-response relations across quintiles of metabolic equivalent value (METs) with DWRT score in participants with or without good self-rated health were found (all p for trend <.001). In participants with poor self-rated heath, compared with the first quintile of METs, those in the fifth quintile (highest METs) had a significantly reduced risk for mild cognitive impairment by 28% (adjusted odds ratio, 0.72; 95% confidence interval, 0.58-0.89, p < .01; p for trend = .006). After additional adjustment for depression, we found that the association between physical activity and DWRT score remained significant. A significant dose-response relationship between physical activity and cognitive function was found, and the association was more pronounced in participants with poor self-rated health. Copyright © 2011 Elsevier Inc. All rights reserved.

Preparation of fast response superabsorbent hydrogels by radiation polymerization and crosslinking of N-isopropylacrylamide in solution

NASA Astrophysics Data System (ADS)

Abd El-Mohdy, H. L.; Safrany, Agnes

2008-03-01

Macroporous temperature-responsive poly( N-isopropylacrylamide) (PNIPAAm) hydrogels with high equilibrium swelling and fast response rates were obtained by a 60Co γ- and electron beam (EB) irradiation of aqueous N-isopropylacrylamide (NIPAAm) monomer solutions. The effect of irradiation temperatures, the dose, the addition of a pore-forming agent on the swelling ratio, and the kinetics of swelling and shrinking of the PNIPAAm gels was studied. The gels synthesized above the LCST exhibited the highest equilibrium swelling (300-400) and fastest response rate measured by minutes. Scanning electron microscope (SEM) pictures revealed that the gels synthesized above the LCST have larger pores than those prepared at temperatures below the LCST. The gels showed a reversible response to cyclical changes in temperature and might be used in a pulsed drug delivery device. The gels synthesized above the LCST exhibited the highest testosterone propionate release.

Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy.

PubMed

Chen, Yingying; Liu, Peng; Chen, Xia; Li, Yanan; Zhang, Fengmei; Wang, Yangang

2018-05-01

There is a lack of research on the effect of low dose of angiotensin receptor blockers combined with spironolactone, and the effect of high dose of angiotensin receptor blockers alone on the urinary albumin excretion rate (UAER) in elderly patients with early type 2 diabetic nephropathy (DN). We conducted a prospective, randomized, open-label, parallel-controlled study that included 244 elderly patients with early DN and mild-to-moderate essential hypertension. Patients were randomly divided into 4 groups: low-dose irbesartan (group A), high-dose irbesartan (group B), low-dose irbesartan combined with spironolactone (group C) and high-dose irbesartan combined with spironolactone (group D). Changes in UAER, serum potassium and blood pressure were compared. There were no statistical differences in the baseline characteristics among groups. Furthermore, no significant difference in blood pressure before and after treatment was found among different groups. After 72-week treatment, UAER in group D was lower compared to group A and B (P < 0.05). Meanwhile, compared with group B, UAER in group C decreased significantly (P < 0.05). Additionally, significantly higher serum potassium was found in group D compared to other groups (P < 0.05). Also, group D had the highest count of patients who withdrew from the study due to hyperkalemia compared to other groups (P < 0.05). Our results indicate high-dose irbesartan combined with spironolactone may be more efficient in reducing UAER in elderly patients with early DN, but this treatment could cause hyperkalemia. Low-dose irbesartan combined with spironolactone was shown to be safer and more effective in decreasing UAER compared to high-dose irbesartan. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Intensity-Modulated Radiotherapy of Head and Neck Cancer Aiming to Reduce Dysphagia: Early Dose-Effect Relationships for the Swallowing Structures

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

Feng, Felix Y.; Kim, Hyungjin M.; Lyden, Teresa H.

2007-08-01

Purpose: To present initial results of a clinical trial of intensity-modulated radiotherapy (IMRT) aiming to spare the swallowing structures whose dysfunction after chemoradiation is a likely cause of dysphagia and aspiration, without compromising target doses. Methods and Materials: This was a prospective, longitudinal study of 36 patients with Stage III-IV oropharyngeal (31) or nasopharyngeal (5) cancer. Definitive chemo-IMRT spared salivary glands and swallowing structures: pharyngeal constrictors (PC), glottic and supraglottic larynx (GSL), and esophagus. Lateral but not medial retropharyngeal nodes were considered at risk. Dysphagia endpoints included objective swallowing dysfunction (videofluoroscopy), and both patient-reported and observer-rated scores. Correlations between dosesmore » and changes in these endpoints from pre-therapy to 3 months after therapy were assessed. Results: Significant correlations were observed between videofluoroscopy-based aspirations and the mean doses to the PC and GSL, as well as the partial volumes of these structures receiving 50-65 Gy; the highest correlations were associated with doses to the superior PC (p = 0.005). All patients with aspirations received mean PC doses >60 Gy or PC V{sub 65} >50%, and GSL V{sub 50} >50%. Reduced laryngeal elevation and epiglottic inversion were correlated with mean PC and GSL doses (p < 0.01). All 3 patients with strictures had PC V{sub 70} >50%. Worsening patient-reported liquid swallowing was correlated with mean PC (p = 0.05) and esophageal (p 0.02) doses. Only mean PC doses were correlated with worsening patient-reported solid swallowing (p = 0.04) and observer-rated swallowing scores (p = 0.04). Conclusions: These dose-volume-effect relationships provide initial IMRT optimization goals and motivate further efforts to reduce swallowing structures doses to reduce dysphagia and aspiration.« less

Predicting in vivo cardiovascular properties of β-blockers from cellular assays: a quantitative comparison of cellular and cardiovascular pharmacological responses

PubMed Central

Baker, Jillian G.; Kemp, Philip; March, Julie; Fretwell, Laurice; Hill, Stephen J.; Gardiner, Sheila M.

2011-01-01

β-Adrenoceptor antagonists differ in their degree of partial agonism. In vitro assays have provided information on ligand affinity, selectivity, and intrinsic efficacy. However, the extent to which these properties are manifest in vivo is less clear. Conscious freely moving rats, instrumented for measurement of heart rate (β1; HR) and hindquarters vascular conductance (β2; HVC) were used to measure receptor selectivity and ligand efficacy in vivo. CGP 20712A caused a dose-dependent decrease in basal HR (P<0.05, ANOVA) at 5 doses between 6.7 and 670 μg/kg (i.v.) and shifted the dose-response curve for isoprenaline to higher agonist concentrations without altering HVC responses. In contrast, at doses of 67 μg/kg (i.v.) and above, ICI 118551 substantially reduced the HVC response to isoprenaline without affecting HR responses. ZD 7114, xamoterol, and bucindolol significantly increased basal HR (ΔHR: +122±12, +129±11, and +59±11 beats/min, respectively; n=6), whereas other β-blockers caused significant reductions (all at 2 mg/kg i.v.). The agonist effects of xamoterol and ZD 7114 were equivalent to that of the highest dose of isoprenaline. Bucindolol, however, significantly antagonized the response to the highest doses isoprenaline. An excellent correlation was obtained between in vivo and in vitro measures of β1-adrenoceptor efficacy (R2=0.93; P<0.0001).—Baker, J. G., Kemp, P., March, J., Fretwell, L., Hill, S. J., Gardiner, S. M. Predicting in vivo cardiovascular properties of β-blockers from cellular assays: a quantitative comparison of cellular and cardiovascular pharmacological responses. PMID:21865315

Irradiated lanoline as a prospective substance for biomedical applications: A spectroscopic and thermal study

NASA Astrophysics Data System (ADS)

Hanzlikova, Zuzana; Hybler, Peter; Fülop, Marko; Ondruska, Jan; Jomova, Klaudia; Porubska, Maria; Valko, Marian

2015-08-01

Refined wool wax products, such as lanoline and lanoline derivatives are key ingredients in some of the ointments, cosmetics, pharmaceuticals, waterproof coatings and other products. Beneficial medicinal effects along with melting point near normal human body temperature designated lanoline to be used in pharmacotherapy and medical treatments. Since the general requirements for sterility of medicinal substances are very strict, especially in cases of skin contact, radiation technologies represent a valuable tool to sterilize the materials for medicinal purposes. In this work, lanoline was irradiated with accelerated electron beam in air within 0-400 kG dose to simulate sterilization for medical purposes. The irradiated lanoline showed considerable fluctuation of chemical structure. The most significant fluctuation was observed for etheric species, followed by ethylene sequences with n<4. While primary and secondary alcohols, as well as epoxides species, decreased below the initial concentration within whole range of the doses, aliphatic esters and ethylene sequences (CH2)n with n≥4 indicated the most stable species. A trace amount of organic-in origin radicals was observed and that increased slightly with dose. Depending on dose, the melting temperature varied from 39.7 to 45.7 °C and the highest values were reached for 25 kGy and 156 kGy. For these same doses the highest thermal stability was also observed and, simultaneously the thermal stability was related inversely to the destruction rate. We propose, that the chemical transformation of lanoline within 0-25 kGy dose should be tested for prospective medical purposes as well as for the need to eliminate remaining outlasting organic-in-origin radicals which were detected in the lanoline even one year after the irradiation.

Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

PubMed

Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

2017-10-01

Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHD<20ng/ml (50nmol/L). A history of falls was collected at baseline and fall events were collected every 3 months. Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-C-BRD-04: Comparison of Shallow Fluence to Deep Point Dose Measurements for Spine VMAT SBRT Patient-Specific QA

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

Cheung, J; Held, M; Morin, O

2015-06-15

Purpose: To investigate the sensitivity of traditional gamma-index-based fluence measurements for patient-specific measurements in VMAT delivered spine SBRT. Methods: The ten most recent cases for spine SBRT were selected. All cases were planned with Eclipse RapidArc for a TrueBeam STx. The delivery was verified using a point dose measurement with a Pinpoint 3D micro-ion chamber in a Standard Imaging Stereotactic Dose Verification Phantom. Two points were selected for each case, one within the target in a low dose-gradient region and one in the spinal cord. Measurements were localized using on-board CBCT. Cumulative and separate arc measurements were acquired with themore » ArcCheck and assessed using the SNC patient software with a 3%/3mm and 2%/2mm gamma analysis with global normalization and a 10% dose threshold. Correlations between data were determined using the Pearson Product-Moment Correlation. Results: For our cohort of patients, the measured doses were higher than calculated ranging from 2.2%–9.7% for the target and 1.0%–8.2% for the spinal cord. There was strong correlation between 3%/3mm and 2%/2mm passing rates (r=0.91). Moderate correlation was found between target and cord dose with a weak fit (r=0.67, R-Square=0.45). The cumulative ArcCheck measurements showed poor correlation with the measured point doses for both the target and cord (r=0.20, r=0.35). If the arcs are assessed separately with an acceptance criteria applied to the minimum passing rate between all arcs, a moderate negative correlation was found for the target and cord (r=−0.48, r= −0.71). The case with the highest dose difference (9.7%) received a passing rate of 97.2% for the cumulative arcs and 87.8% for the minimum with separate arcs. Conclusion: Our data suggest that traditional passing criteria using ArcCheck with cumulative measurements do not correlate well with dose errors. Separate arc analysis shows better correlation but may still miss large dose errors. Point dose verifications are recommended.« less

Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level.

PubMed

Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

2015-12-01

The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h(-1) up to 1.5 Gy h(-1). Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h(-1). A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR10) was estimated at 95 ± 7 mGy h(-1), followed by 153 ± 13 mGy h(-1) and 169 ± 12 mGy h(-1) on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h(-1), antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h(-1) which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic stress conditions can induce endoreduplication events. Here an increase in ploidy level was observed at the highest tested dose rate. In conclusion, the results revealed that in plants several mechanisms and pathways interplay to cope with radiation induced stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative Assessment of Heterogeneity in Tumor Metabolism Using FDG-PET

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

Vriens, Dennis, E-mail: d.vriens@nucmed.umcn.nl; Disselhorst, Jonathan A.; Oyen, Wim J.G.

2012-04-01

Purpose: [{sup 18}F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) images are usually quantitatively analyzed in 'whole-tumor' volumes of interest. Also parameters determined with dynamic PET acquisitions, such as the Patlak glucose metabolic rate (MR{sub glc}) and pharmacokinetic rate constants of two-tissue compartment modeling, are most often derived per lesion. We propose segmentation of tumors to determine tumor heterogeneity, potentially useful for dose-painting in radiotherapy and elucidating mechanisms of FDG uptake. Methods and Materials: In 41 patients with 104 lesions, dynamic FDG-PET was performed. On MR{sub glc} images, tumors were segmented in quartiles of background subtracted maximum MR{sub glc} (0%-25%, 25%-50%, 50%-75%, and 75%-100%).more » Pharmacokinetic analysis was performed using an irreversible two-tissue compartment model in the three segments with highest MR{sub glc} to determine the rate constants of FDG metabolism. Results: From the highest to the lowest quartile, significant decreases of uptake (K{sub 1}), washout (k{sub 2}), and phosphorylation (k{sub 3}) rate constants were seen with significant increases in tissue blood volume fraction (V{sub b}). Conclusions: Tumor regions with highest MR{sub glc} are characterized by high cellular uptake and phosphorylation rate constants with relatively low blood volume fractions. In regions with less metabolic activity, the blood volume fraction increases and cellular uptake, washout, and phosphorylation rate constants decrease. These results support the hypothesis that regional tumor glucose phosphorylation rate is not dependent on the transport of nutrients (i.e., FDG) to the tumor.« less

Risk assessment of skin lightening cosmetics containing hydroquinone.

PubMed

Matsumoto, Mariko; Todo, Hiroaki; Akiyama, Takumi; Hirata-Koizumi, Mutsuko; Sugibayashi, Kenji; Ikarashi, Yoshiaki; Ono, Atsushi; Hirose, Akihiko; Yokoyama, Kazuhito

2016-11-01

Following reports on potential risks of hydroquinone (HQ), HQ for skin lightening has been banned or restricted in Europe and the US. In contrast, HQ is not listed as a prohibited or limited ingredient for cosmetic use in Japan, and many HQ cosmetics are sold without restriction. To assess the risk of systemic effects of HQ, we examined the rat skin permeation rates of four HQ (0.3%, 1.0%, 2.6%, and 3.3%) cosmetics. The permeation coefficients ranged from 1.2 × 10 -9 to 3.1 × 10 -7  cm/s, with the highest value superior than the HQ aqueous solution (1.6 × 10 -7  cm/s). After dermal application of the HQ cosmetics to rats, HQ in plasma was detected only in the treatment by highest coefficient cosmetic. Absorbed HQ levels treated with this highest coefficient cosmetic in humans were estimated by numerical methods, and we calculated the margin of exposure (MOE) for the estimated dose (0.017 mg/kg-bw/day in proper use) to a benchmark dose for rat renal tubule adenomas. The MOE of 559 is judged to be in a range safe for the consumer. However, further consideration may be required for regulation of cosmetic ingredients. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of chancroid in resource-poor countries.

PubMed

Annan, Naa Torshie; Lewis, David A

2005-04-01

Chancroid, formerly a major cause of the genital ulcer disease syndrome, remains an important cofactor in both the transmission and acquisition of HIV-1 infection. Those countries with the greatest burden of HIV also have some of the highest prevalence rates of chancroid worldwide. The diagnosis of chancroid, caused by the fastidious bacterium Haemophilus ducreyi, is both expensive and difficult in many resource-poor areas. These areas of the world use syndromic management to treat genital ulcers and such an approach has proven effective in reducing rates of bacterial genital ulcer diseases. There are currently inexpensive and effective single-dose therapies available to treat chancroid. Single-dose regimens, given at first presentation, improve compliance and reduce the risk of sexually transmitted infections. Bacterial resistance to several antimicrobial agents has increased over the years and remains a continued threat to effective antimicrobial therapy. Follow-up of cases, and partner notification and treatment is carried out to limit reinfection and onward transmission of chancroid. Patients with coexistent HIV may be particularly at risk of failing single-dose therapy and should therefore be reviewed wherever possible.

The subjective experience of trauma and subsequent PTSD in a sample of undocumented immigrants.

PubMed

Rasmussen, Andrew; Rosenfeld, Barry; Reeves, Kim; Keller, Allen S

2007-02-01

Although a subjective component of trauma is commonly recognized in diagnosing posttraumatic stress disorder (PTSD), there are few studies that specifically address Criterion A2, and none addressing this issue among undocumented immigrants. We assessed 212 arriving undocumented immigrants with diverse trauma histories to investigate concordance between objective and subjective factors of trauma (Criteria A1 and A2) and across different types of trauma and PTSD. Concordance between Criteria A1 and A2 varied, with highest rates found for political violence. Interpersonal violence in general was associated with higher rates of PTSD. We identified a dose-response effect for PTSD, but this was not dependent on other events (i.e., other doses) meeting Criterion A2. Discussion focuses on Criterion A within the phenomenology of PTSD and the need to gauge subjective interpretations of trauma events among this population.

Assessment of normal tissue complications following prostate cancer irradiation: Comparison of radiation treatment modalities using NTCP models

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

Takam, Rungdham; Bezak, Eva; Yeoh, Eric E.

2010-09-15

Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences inmore » radiation treatment modality and fractionation schedule. Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower equivalent doses compared to other tissues.« less

The pathology of americium 241.

PubMed

Nilsson, A; Broomé-Karlsson, A

1976-02-01

Male CBA-mice were injected intraperitoneally with different doses of 241Am-citrate (16, 8, 0.4, 0.2, 0.04 muCi/kg). The two highest doses were highly destructive of the haematopoietic tissues, testes and bone tissue. The highest frequency of induced tumours of the skeleton and haematopoietic tissue was found in the 8 muCi group. In the liver, adrenal glands, kidney and heart degenerative lesions were found mainly in the higher dose groups. In the lower dose groups degenerative lesions seemed to appear earlier and at a higher frequency than in the control group.

Evaluation and decontamination of crude oil-polluted soils using Centrosema pubescen Benth and amendment-support options.

PubMed

Nwaichi, Eucharia O; Osuji, Leo C; Onyeike, Eugene N

2011-04-01

Growth performance and phytoremediation of soil of the Niger Delta Region of Nigeria artificially-contaminated with crude oil (up to 100 mL/2 kg soil) using centrosema pubescen Benth was investigated for 12 weeks. The soil samples in which the plants were established were either un-amended, or amended with NPK, or UREA or chicken manure. The extents of removal of PAHs and BTEX were measured as well as the rates of growth of the plants. Gas Chromatographic analysis confirmed the degradation of carcinogenic hydrocarbons like BTEXs and PAHs with this technique. At the highest dose of crude, the contaminant concentrations were 43 mg/kg PAHs, 10 mg/kg BTEX, and 5,613 mg/kg O&G. The greatest percent removal of BTEX was observed at the highest contaminant dose, and with the manure amendment. Similar trends were observed with PAHs and although they were less marked, the trends with PAHs may have been more highly statistically significant. There was no measurable plant uptake of contaminants. Inhibition of plant growth (measured as leaf area, shoot length and production of dry weight) was proportional to the dose of crude oil, but the manure amendment was very effective at reducing the growth inhibition. Interestingly, manure amendment reduced the phytotoxicity significantly in this study.

Radiation lethality in the opossum

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

Prasad, N.; Bushong, S.C.; North, L.B.

1976-12-01

Groups of male opossum (Didelphis virginiana) at 6 months of age were exposed to 350, 500, 550, 600, 650, 700, and 750 rad of whole-body /sup 60/Co radiation at a midline dose rate of 125 rad/min. The 30-day LD/sub 50/ was 511 rad with 95% confidence limits of 454 to 576 rad. The overall mean survival time was 17.9 days and the highest incidence of death occurred on the 16th day.

Acute Biological Effects of Simulating the Whole-Body Radiation Dose Distribution from a Solar Particle Event Using a Porcine Model

PubMed Central

Wilson, Jolaine M.; Sanzari, Jenine K.; Diffenderfer, Eric S.; Yee, Stephanie S.; Seykora, John T.; Maks, Casey; Ware, Jeffrey H.; Litt, Harold I.; Reetz, Jennifer A.; McDonough, James; Weissman, Drew; Kennedy, Ann R.; Cengel, Keith A.

2011-01-01

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses. PMID:21859326

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

SU-E-T-598: Clinical Experience of Configuration, Commission and Implementation for SmartArc with MOSAIQ R&V System.

PubMed

Kong, X; Clausen, C; Wang, S

2012-06-01

Clinical experience for configuration, commission and implementation of SmartArc with MOSAIQ R&V system. SmartArc is Pinnacle's solution for VMAT. On July 2011 we updated to Pinnacle 9.0 and purchased SmartArc. A standalone Eclipse workstation has been used 3 years for VMAT planning. Our clinical setting: Mosaiq 2.2; Varian Trilogy driven by 4DiTC and Varian 21ex driven by sequencer. Some key physics parameters have been studied: machine dose rate; MLC leaf speed; Leaf motion per gantry rotation. Tabletop was created by user to improve the dose accuracy for planning. In-house sandwich phantom was used with MapCheck for planner dose verification. A PTW 0.6cc ion chamber was included for absolute dose comparison. A copy of current machine data with default highest dose rate is recommended. It is due to after 10th iteration of optimization, the default dose rate will kick in. 2.5cm/s is the constraint for Varian Millennium 120 MLC; a buffer zone of 10% is suggested to reduce the MLC error on treatment. 2.25cm/s is used in our configuration. This results in MLC interlock if not configured correct. Maximum leaf motion per gantry rotation of 0.46cm/degree has to be checked for planning with Mosaiq R&V. Otherwise, undeliverable plan will show up sometimes on 4DiTC.Tabletop was exported as a DICOM structure from Eclipse to Pinnacle; we created a ROI template based on the matched tabletop.QA using in-house phantom for different sites were tested. Results for both planner dose and absolute chamber measurement are satisfactory. Special attentions need to be paid for dose rate, MLC leaf speed, leaf motion per gantry rotation when configuring SmartArc. Varian 21ex is supported but is slow for clinical delivery. Users need to create your own tabletop to improve planning accuracy. Conventional commission procedures for RapidArc also apply for SmartArc. © 2012 American Association of Physicists in Medicine.

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

PubMed

Sulkes, A; Benner, S E; Canetta, R M

1998-10-01

This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

Proarrhythmic potential of halofantrine, terfenadine and clofilium in a modified in vivo model of torsade de pointes

PubMed Central

Batey, Andrew J; Coker, Susan J

2002-01-01

This study was designed to compare the proarrhythmic activity of the antimalarial drug, halofantrine and the antihistamine, terfenadine, with that of clofilium a K+ channel blocking drug that can induce torsade de pointes. Experiments were performed in pentobarbitone-anaesthetized, open-chest rabbits. Each rabbit received intermittent, rising dose i.v. infusions of the α-adrenoceptor agonist phenylephrine. During these infusions rabbits also received increasing i.v. doses of clofilium (20, 60 and 200 nmol kg−1 min−1), terfenadine (75, 250 and 750 nmol kg−1 min−1), halofantrine (6, 20 and 60 μmol kg−1) or vehicle. Clofilium and halofantrine caused dose-dependent increases in the rate-corrected QT interval (QTc), whereas terfenadine prolonged PR and QRS intervals rather than prolonging cardiac repolarization. Progressive bradycardia occurred in all groups. After administration of the highest dose of each drug halofantrine caused a modest decrease in blood pressure, but terfenadine had profound hypotensive effects resulting in death of most rabbits. The total number of ventricular premature beats was highest in the clofilium group. Torsade de pointes occurred in 6 out of 8 clofilium-treated rabbits and 4 out of 6 of those which received halofantrine, but was not seen in any of the seven terfenadine-treated rabbits. These results show that, like clofilium, halofantrine can cause torsade de pointes in a modified anaesthetized rabbit model whereas the primary adverse effect of terfenadine was cardiac contractile failure. PMID:11861329

Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies.

PubMed

Hart, R G; Pearce, L A; Miller, V T; Anderson, D C; Rothrock, J F; Albers, G W; Nasco, E

2000-01-01

While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic. To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies. On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I-III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy. Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05). Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin. Copyright 2000 S. Karger AG, Basel

Acute effect of ivabradine on heart rate and myocardial oxygen consumption in dogs with asymptomatic mitral valve degeneration.

PubMed

Pirintr, Prapawadee; Limprasutr, Vudhiporn; Saengklub, Nakkawee; Pavinadol, Parnpradub; Yapao, Napat; Limvanicharat, Natthakarn; Kuecharoen, Hathaisiri; Kijtawornrat, Anusak

2018-05-14

Degenerative mitral valve disease (DMVD) is a common cardiac disease in geriatric dogs characterized by the degeneration of the mitral valve, leading to decreased cardiac output and activation of the sympathetic and renin-angiotensin-aldosterone system. This disease results in an increased resting heart rate (HR) and myocardial oxygen consumption (MVO 2 ). A recent publication demonstrated that dogs with asymptomatic DMVD had a significantly higher HR and systemic blood pressure (BP) than age-matched control dogs. This higher HR will eventually contribute to increased MVO 2 . This study aimed to determine the effects of a single oral dose of ivabradine on the HR, MVO 2 as assessed by the rate-pressure product, and BP in dogs with asymptomatic DMVD. Seven beagles with naturally occurring DMVD were instrumented by the Holter recorder and an oscillometric device to measure electrocardiogram and BP for 24 and 12 h, respectively. Each dog was randomly subjected to receive either placebo or ivabradine (0.5, 1.0 and 2.0 mg/kg). The results revealed that oral administration of ivabradine significantly decreased the HR and rate-pressure product in a dose-dependent manner without adverse effects. The highest dose of 2.0 mg/kg significantly reduced systolic and mean BP. Therefore, the findings imply that a single oral ivabradine administration at a dose of 1.0 mg/kg is suitable for dogs with asymptomatic DMVD to reduce the HR and MVO 2 without marked effects on BP. This may potentially make ivabradine promising for management of an elevated HR in DMVD dogs.

Uptake and toxicity of glyphosate in the lichen Xanthoria parietina (L.) Th. Fr.

PubMed

Vannini, Andrea; Guarnieri, Massimo; Bačkor, Martin; Bilová, Ivana; Loppi, Stefano

2015-12-01

This study investigated if treatment of the lichen Xanthoria parietina (L.) Th. Fr. with glyphosate caused uptake of this herbicide as well as physiological alterations. Samples were treated with Glifene SL®, a common commercial glyphosate-based herbicide, at the lowest recommended doses (3.6g/L) as well as with doses slightly higher than the highest suggested (36 g/L). The results clearly showed glyphosate uptake in X. parietina proportionally to the dose provided. Adverse physiological effects were evident on the photosynthetic apparatus (photosynthetic efficiency, chlorophyll a content, chlorophyll degradation) as well as on the fungal respiration rates and cell membrane integrity (ergosterol content, dehydrogenase activity) already after 24h from treatment, also at the low application dose. It is concluded that lichens are suitable organisms for monitoring unwanted biological effects from the application of glyphosate-based herbicides, as well as for detecting the accumulation of this compound in the biota, thus screening for its environmental fate. Copyright © 2015 Elsevier Inc. All rights reserved.

Radioactive contamination of arthropods from different trophic levels in hilly and mountainous areas after the Fukushima Daiichi nuclear power plant accident.

PubMed

Tanaka, Sota; Hatakeyama, Kaho; Takahashi, Sentaro; Adati, Tarô

2016-11-01

In order to understand the influence of the Fukushima Daiichi nuclear power plant accident on the ecosystem in hilly and mountainous areas of Fukushima Prefecture, chronological changes in the levels of radiocesium in arthropod species were investigated. From 2012 to 2014, arthropods from different trophic levels were sampled and the air radiation dose rates at the sampling sites were analyzed. The air radiation dose rates showed a significant and constant reduction over the 2 years at the sampling sites in Fukushima. The median radiocesium concentration ( 134 Cs +  137 Cs) detected in the rice grasshopper, Oxya yezoensis, and the Emma field cricket, Teleogryllus emma, dropped continuously to 0.080 and 0.078 Bq/g fresh weight, respectively, in 2014. In contrast, no significant reduction in radioactive contamination was observed in the Jorô spider, Nephila clavata, in which the level remained at 0.204 Bq/g in 2014. A significant positive correlation between radiocesium concentration and the air radiation dose rate was observed in the rice grasshopper, the Emma field cricket and the Jorô spider. The highest correlation coefficient (ρ = 0.946) was measured in the grasshopper. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Metabolic Conversion of Ceramides in HeLa Cells - A Cholesteryl Phosphocholine Delivery Approach

PubMed Central

Kjellberg, Matti A.; Lönnfors, Max; Slotte, J. Peter; Mattjus, Peter

2015-01-01

Ceramides can be delivered to cultured cells without solvents in the form of complexes with cholesteryl phosphocholine. We have analysed the delivery of three different radiolabeled D-erythro-ceramides (C6-Cer, C10-Cer and C16-Cer) to HeLa cells, and followed their metabolism as well as the cell viability. We found that all three ceramides were successfully taken up by HeLa cells when complexed to CholPC in an equimolar ratio, and show that the ceramides show different rates of cellular uptake and metabolic fate. The C6-Cer had the highest incorporation rate, followed by C10-Cer and C16-Cer, respectively. The subsequent effect on cell viability strongly correlated with the rate of incorporation, where C6-Cer had the strongest apoptotic effects. Low-dose (1 μM) treatment with C6-Cer favoured conversion of the precursor to sphingomyelin, whereas higher concentrations (25–100 μM) yielded increased conversion to C6-glucosylceramide. Similar results were obtained for C10-Cer. In the lower-dose C16-Cer experiments, most of the precursor was degraded, whereas at high-dose concentrations the precursor remained un-metabolized. Using this method, we demonstrate that ceramides with different chain lengths clearly exhibit varying rates of cellular uptake. The cellular fate of the externally delivered ceramides are clearly connected to their rate of incorporation and their subsequent effects on cell viability may be in part determined by their chain length. PMID:26599810

Key parameters and practices controlling pesticide degradation efficiency of biobed substrates.

PubMed

Karanasios, Evangelos; Karpouzas, Dimitrios G; Tsiropoulos, Nikolaos G

2012-01-01

We studied the contribution of each of the components of a compost-based biomixture (BX), commonly used in Europe, on pesticide degradation. The impact of other key parameters including pesticide dose, temperature and repeated applications on the degradation of eight pesticides, applied as a mixture, in a BX and a peat-based biomixture (OBX) was compared and contrasted to their degradation in soil. Incubation studies showed that straw was essential in maintaining a high pesticide degradation capacity of the biomixture, whereas compost, when mixed with soil, retarded pesticide degradation. The highest rates of degradation were shown in the biomixture composed of soil/compost/straw suggesting that all three components are essential for maximum biobed performance. Increasing doses prolonged the persistence of most pesticides with biomixtures showing a higher tolerance to high pesticide dose levels compared to soil. Increasing the incubation temperature from 15 °C to 25 °C resulted in lower t(1/2) values, with biomixtures performing better than soil at the lower temperature. Repeated applications led to a decrease in the degradation rates of most pesticides in all the substrates, with the exception of iprodione and metalaxyl. Overall, our results stress the ability of biomixtures to perform better than soil under unfavorable conditions and extreme pesticide dose levels. Copyright © Taylor & Francis Group, LLC

Variations of radon concentration in the atmosphere. Gamma dose rate

NASA Astrophysics Data System (ADS)

Tchorz-Trzeciakiewicz, D. E.; Solecki, A. T.

2018-02-01

The purposes of research were following: observation and interpretation of variations of radon concentration in the atmosphere - vertical, seasonal, spatial and analysis of relation between average annual radon concentration and ground natural radiation and gamma dose rate. Moreover we wanted to check the occurrence of radon density currents and the possibility of radon accumulation at the foot of the spoil tip. The surveys were carried out in Okrzeszyn (SW Poland) in the area of the spoil tip formed during uranium mining that took place in 60's of 20th century. The measurements were carried out in 20 measurements points at three heights: 0.2 m, 1 m and 2 m a.g.l. using SSNTD LR-115. The survey lasted one year and detectors were exchanged at the beginning of every season. Uranium eU (ppm), thorium eTh (ppm) and potassium K (%) contents were measured using gamma ray spectrometer Exploranium RS-230, ambient gamma dose rate using radiometer RK-100. The average radon concentration on this area was 52.8 Bq m-3. The highest radon concentrations were noted during autumn and the lowest during winter. We observed vertical variations of radon concentration. Radon concentrations decreased with increase of height above ground level. The decrease of radon with increase of height a.g.l. had logarithmic character. Spatial variations of radon concentrations did not indicate the occurrence of radon density currents and accumulation of radon at the foot of the spoil tip. The analysis of relation between average radon concentrations and ground natural radiation (uranium and thorium content) or gamma dose rate revealed positive relation between those parameters. On the base of results mentioned above we suggested that gamma spectrometry measurements or even cheaper and simpler ambient gamma dose rate measurements can be a useful tool in determining radon prone areas. This should be confirmed by additional research.

M-BAND Study of Radiation-Induced Chromosome Aberrations in Human Epithelial Cells: Radiation Quality and Dose Rate Effects

NASA Technical Reports Server (NTRS)

Hada, Megumi; Cucinotta, Francis; Wu, Honglu

2009-01-01

The advantage of the multicolor banding in situ hybridization (mBAND) technique is its ability to identify both inter- (translocation to unpainted chromosomes) and intra- (inversions and deletions within a single painted chromosome) chromosome aberrations simultaneously. To study the detailed rearrangement of low- and high-LET radiation induced chromosome aberrations in human epithelial cells (CH184B5F5/M10) in vitro, we performed a series of experiments with Cs-137 gamma rays of both low and high dose rates, neutrons of low dose rate and 600 MeV/u Fe ions of high dose rate, with chromosome 3 painted with multi-binding colors. We also compared the chromosome aberrations in both 2- and 3-dimensional cell cultures. Results of these experiments revealed the highest chromosome aberration frequencies after low dose rate neutron exposures. However, detailed analysis of the radiation induced inversions revealed that all three radiation types induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intra-chromosomal aberrations but few inversions were accompanied by inter-chromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosomal exchanges. The location of the breaks involved in chromosome exchanges was analyzed along the painted chromosome. The breakpoint distribution was found to be randomly localized on chromosome 3 after neutron or Fe ion exposure, whereas non-random distribution with clustering breakpoints was observed after -ray exposure. Our comparison of chromosome aberration yields between 2- and 3-dimensional cell cultures indicated a significant difference for gamma exposures, but not for Fe ion exposures. These experimental results indicated that the track structure of the radiation and the cellular/chromosome structure can both affect radiation-induced chromosome aberrations.

Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat

PubMed Central

Nekooeian, Ali A; Tabrizchi, Reza

1998-01-01

The effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output, blood pressure, mean circulatory filling pressure (Pmcf), arterial and venous resistances, heart rate and left ventricular end-diastolic pressure were assessed in rats with acute heart failure by means of coronary artery occlusion.Animals (n=6 in each group) were divided into five groups: group I, sham-operated vehicle-treated (0.9% saline; 0.018 mL min−1); groups II-V, subject to coronary artery occlusion and treated with vehicle (0.9% saline; 0.018 ml min−1) and CGS 21680 (0.1, 0.3 and 1.0 μg kg−1 min−1), respectively. Haemodynamic measurements were taken one hour after completion of surgery, ninety minutes after coronary artery occlusion (except in group I), and fifteen minutes after infusion of saline or CGS 21680.Baseline haemodynamic measurements before occlusion were found not to differ significantly between the different groups of animals. However, after occlusion, cardiac output, rate of rise in left ventricular pressure (+dP/dt) and blood pressure were significantly reduced when compared to corresponding values in sham-operated animals. In addition, occlusion of the coronary artery resulted in a significant elevation in venous resistance, Pmcf and left ventricular end-diastolic pressure as compared to corresponding values in sham-operated animals.Infusion with CGS 21680 at the highest dose significantly reduced blood pressure, arterial resistance and left ventricular end-diastolic pressure when compared to occluded vehicle-treated animals (group II). Administration of CGS 21680 at the highest dose also significantly increased cardiac output (28%) and heart rate (10%) in comparison to occluded vehicle-treated animals. In addition, the highest dose of CGS 21680 significantly reduced Pmcf (9%) and venous resistance (62%) in comparison to occluded vehicle-treated animals. Administration of CGS 21680 did not significantly affect +dP/dt when compared to occluded vehicle-treated animals.The results from the present investigation indicate that occlusion of the coronary artery in rats results in a state of heart failure characterized by reduced arterial pressure and cardiac output, and increased venous resistance, Pmcf and left ventricular end-diastolic pressure. Administration of CGS 21680 to animals with acute heart failure resulted in increased cardiac output which was due to reduced venous resistance, as well as increased heart rate. PMID:9605574

Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat.

PubMed

Nekooeian, A A; Tabrizchi, R

1998-04-01

1. The effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output, blood pressure, mean circulatory filling pressure (Pmcf), arterial and venous resistances, heart rate and left ventricular end-diastolic pressure were assessed in rats with acute heart failure by means of coronary artery occlusion. 2. Animals (n=6 in each group) were divided into five groups: group I, sham-operated vehicle-treated (0.9% saline; 0.018 mL min(-1)); groups II-V, subject to coronary artery occlusion and treated with vehicle (0.9% saline; 0.018 ml min(-1)) and CGS 21680 (0.1, 0.3 and 1.0 microg kg(-1) min(-1)), respectively. Haemodynamic measurements were taken one hour after completion of surgery, ninety minutes after coronary artery occlusion (except in group I), and fifteen minutes after infusion of saline or CGS 21680. 3. Baseline haemodynamic measurements before occlusion were found not to differ significantly between the different groups of animals. However, after occlusion, cardiac output, rate of rise in left ventricular pressure (+ dP/dt) and blood pressure were significantly reduced when compared to corresponding values in sham-operated animals. In addition, occlusion of the coronary artery resulted in a significant elevation in venous resistance, Pmcf and left ventricular end-diastolic pressure as compared to corresponding values in sham-operated animals. 4. Infusion with CGS 21680 at the highest dose significantly reduced blood pressure, arterial resistance and left ventricular end-diastolic pressure when compared to occluded vehicle-treated animals (group II). Administration of CGS 21680 at the highest dose also significantly increased cardiac output (28%) and heart rate (10%) in comparison to occluded vehicle-treated animals. In addition, the highest dose of CGS 21680 significantly reduced Pmcf (9%) and venous resistance (62%) in comparison to occluded vehicle-treated animals. Administration of CGS 21680 did not significantly affect +dP/dt when compared to occluded vehicle-treated animals. 5. The results from the present investigation indicate that occlusion of the coronary artery in rats results in a state of heart failure characterized by reduced arterial pressure and cardiac output, and increased venous resistance, Pmcf and left ventricular end-diastolic pressure. Administration of CGS 21680 to animals with acute heart failure resulted in increased cardiac output which was due to reduced venous resistance, as well as increased heart rate.

Probabilistic dose assessment of normal operations and accident conditions for an assured isolation facility in Texas

NASA Astrophysics Data System (ADS)

Arno, Matthew Gordon

Texas is investigating building a long-term waste storage facility, also known as an Assured Isolation Facility. This is an above-ground low-level radioactive waste storage facility that is actively maintained and from which waste may be retrieved. A preliminary, scoping-level analysis has been extended to consider more complex scenarios of radiation streaming and skyshine by using the computer code Monte Carlo N-Particle (MCNP) to model the facility in greater detail. Accidental release scenarios have been studied in more depth to better assess the potential dose to off-site individuals. Using bounding source term assumptions, the projected radiation doses and dose rates are estimated to exceed applicable limits by an order of magnitude. By altering the facility design to fill in the hollow cores of the prefabricated concrete slabs used in the roof over the "high-gamma rooms," where the waste with the highest concentration of gamma emitting radioactive material is stored, dose rates outside the facility decrease by an order of magnitude. With the modified design, the annual dose at the site fenceline is estimated at 86 mrem, below the 100 mrem annual limit for exposure of the public. Within the site perimeter, the dose rates are lowered sufficiently such that it is not necessary to categorize many workers and contractor personnel as radiation workers, saving on costs as well as being advisable under ALARA principles. A detailed analysis of bounding accidents incorporating information on the local meteorological conditions indicate that the maximum committed effective dose equivalent from the passage of a plume of material released in an accident at any of the cities near the facility is 59 :rem in the city of Eunice, NM based on the combined day and night meteorological conditions. Using the daytime meteorological conditions, the maximum dose at any city is 7 :rem, also in the city of Eunice. The maximum dose at the site boundary was determined to be 230 mrem using the combined day and night meteorological conditions and 33 mrem using the daytime conditions.

Safety and Immunogenicity of Cell Culture-Derived A/H3N2 Variant Influenza Vaccines: A Phase I Randomized, Observer-Blind, Dose-Ranging Study.

PubMed

Johnson, Casey; Hohenboken, Matthew; Poling, Terry; Jaehnig, Peter; Kanesa-Thasan, Niranjan

2015-07-01

A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important. In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥ 3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data. Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3-<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate. A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations. ClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945). © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

PubMed Central

Häfner, D.; Beume, R.; Kilian, U.; Krasznai, G.; Lachmann, B.

1995-01-01

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 Figure 3 Figure 4 PMID:7582456

An effective dose of ketamine for eliminating pain during injection of propofol: a dose response study.

PubMed

Wang, M; Wang, Q; Yu, Y Y; Wang, W S

2013-09-01

Ketamine can completely eliminate pain associated with propofol injection. However, the effective dose of ketamine to eliminate propofol injection pain has not been determined. The purpose of this study was to determine the effective dose of ketamine needed to eliminate pain in 50% and 95% of patients (ED50 and ED95, respectively) during propofol injections. This study was conducted in a double-blinded fashion and included 50 patients scheduled for elective gynecological laparoscopy under general anesthesia. The initial dose of ketamine used in the first patient was 0.25mg/kg. The dosing modifications were in increments or decrements of 0.025 mg/kg. Ketamine was administered 15 seconds before injecting propofol (2.5mg/kg), which was injected at a rate of 1mL/s. Patients were asked to rate their pain during propofol injection every 5s econds using a 0-3 pain scale. The highest pain score was recorded. The ED50, ED95 and 95% confidence intervals (CI) were determined by probit analyses. The dose of ketamine ranged from 0.175 to 0.275 mg/kg. The ED50 and ED95 of ketamine for eliminating pain during propofol injection were 0.227 mg/kg and 0.283 mg/kg, respectively (95%CI: 0.211-0.243 mg/kg and 0.26-0.364 mg/kg, respectively). Ketamine at an approximate dose of 0.3mg/kg was effective in eliminating pain during propofol injection. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Six steps to a successful dose-reduction strategy

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

Bennett, M.

1995-03-01

The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3)more » prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management.« less

Effects of intra-aortic balloon counterpulsation in a model of septic shock.

PubMed

Solomon, Steven B; Minneci, Peter C; Deans, Katherine J; Feng, Jing; Eichacker, Peter Q; Banks, Steven M; Danner, Robert L; Natanson, Charles; Solomon, Michael A

2009-01-01

Fluid refractory septic shock can develop into a hypodynamic cardiovascular state in both children and adults. Despite management of these patients with empirical inotropic therapy (with or without a vasodilator), mortality remains high. The effect of cardiovascular support using intra-aortic balloon counterpulsation was investigated in a hypodynamic, mechanically ventilated canine sepsis model in which cardiovascular and pulmonary support were titrated based on treatment protocols. Each week, three animals (n = 33, 10-12 kg) were administered intrabronchial Staphylococcus aureus challenge and then randomized to receive intra-aortic balloon counterpulsation for 68 hrs or no intra-aortic balloon counterpulsation (control). Bacterial doses were increased over the study (4-8 x 10(9) cfu/kg) to assess the effects of intra-aortic balloon counterpulsation during sepsis with increasing risk of death. Compared with lower bacterial doses (4-7 x 10(9) colony-forming units/kg), control animals challenged with the highest dose (8 x 10(9) colony-forming units/kg) had a greater risk of death (mortality rate 86% vs. 17%), with worse lung injury ([A - a]O2), and renal dysfunction (creatinine). These sicker animals required higher norepinephrine infusion rates to maintain blood pressure (and higher FIO2) and positive end-expiratory pressure levels to maintain oxygenation (p < or = 0.04 for all). In animals receiving the highest bacterial dose, intra-aortic balloon counterpulsation improved survival time (23.4 +/- 10 hrs longer; p = 0.003) and lowered norepinephrine requirements (0.43 +/- 0.17 microg/kg/min; p = 0.002) and systemic vascular resistance index (1.44 +/- 0.57 dynes/s/cm5/kg; p = 0.0001) compared with controls. Despite these beneficial effects, intra-aortic balloon counterpulsation was associated with an increase in blood urea nitrogen (p = 0.002) and creatinine (p = 0.12). In animals receiving lower doses of bacteria, intra-aortic balloon counterpulsation had no significant effects on survival or renal function. In a canine model of severe septic shock with a low cardiac index, intra-aortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements.

Evaluation of safety and immunogenicity of a live attenuated tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus vaccine (BRV-TV) in healthy Indian adults and infants.

PubMed

Dhingra, M S; Kundu, R; Gupta, M; Kanungo, S; Ganguly, N; Singh, M P; Bhattacharya, M K; Ghosh, R; Kumar, R; Sur, D; Chadha, S M; Saluja, T

2014-08-11

Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6-8, 10-12 and 14-16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 10(5.0) FFU, 10(5.8) FFU, 10(6.4) FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10(6.4) FFU had a higher sero-response rate compared to the active comparator arm (RotaTeq), 28 days post each vaccine dose. The safety profile was comparable across the treatment groups. Overall, the results showed that all three doses of BRV-TV vaccine were safe, well tolerated and displayed good immunogenicity (dose-response) in healthy Indian infants. Copyright © 2014. Published by Elsevier Ltd.

Detection and distribution of ostreid herpesvirus 1 in experimentally infected Pacific oyster spat.

PubMed

Segarra, Amélie; Baillon, Laury; Faury, Nicole; Tourbiez, Delphine; Renault, Tristan

2016-01-01

High mortality rates are reported in spat and larvae of Pacific oyster Crassostrea gigas and associated with ostreid herpesvirus 1 (OsHV-1) detection in France. Although the viral infection has been experimentally reproduced in oyster larvae and spat, little knowledge is currently available concerning the viral entry and its distribution in organs and tissues. This study compares OsHV-1 DNA and RNA detection and localization in experimentally infected oysters using two virus doses: a low dose that did not induce any mortality and a high dose inducing high mortality. Real time PCR demonstrated significant differences in terms of viral DNA amounts between the two virus doses. RNA transcripts were detected in oysters receiving the highest dose of viral suspension whereas no transcript was observed in oysters injected with the low dose. This study also allowed observing kinetics of viral DNA and RNA detection in different tissues of oyster spat. Finally, viral detection was significantly different in function of tissues (p<0.005), time (p<0.005) with an interaction between tissues and time (p<0.005) for each probe. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of gamma irradiation on the thiamine, riboflavin and vitamin B 6 content in two varieties of Brazilian beans

NASA Astrophysics Data System (ADS)

Villavicencio, A. L. C. H. A. L. C. H.; Mancini-Filho, J. J.; Delincée, H. H.; Bognár, A. A.

2000-03-01

The effect of 60Co gamma rays on the content of several B-vitamins in two varieties of Brazilian beans has been studied. Carioca ( Phaseolus vulgaris L. var. Carioca) and Macaçar beans ( Vigna unguiculata L. Walp, var. Macaçar) were irradiated at doses of 0, 0.5, 1.0, 2.5, 5.0 and 10 kGy, and subsequently stored at ambient temperature for 6 months. The content of vitamin B 1, B 2 and B 6 was analysed by HPLC. In addition, the optimum cooking time was established for each dose and bean variety. A taste panel evaluated sensory properties. Only slight changes were measured for thiamine and riboflavin, whereas a dose-dependent decrease was noted for pyridoxine, which, however, was significant only at the highest doses of 5 and 10 kGy. Cooking time was considerably reduced with increasing radiation dose, but accompanied by a loss of the sensory quality. However, at the disinfestation dose up to 1 kGy, acceptable ratings were obtained for the sensory evaluation. In conclusion, for insect disinfestation of Brazilian beans radiation processing is a promising technology.

Efficacy and tolerability of brivaracetam compared to lacosamide, eslicarbazepine acetate, and perampanel as adjunctive treatments in uncontrolled focal epilepsy: Results of an indirect comparison meta-analysis of RCTs.

PubMed

Brigo, Francesco; Bragazzi, Nicola Luigi; Nardone, Raffaele; Trinka, Eugen

2016-11-01

Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) have been recently marketed as adjunctive treatments for focal onset seizures. To date, no randomized controlled trial (RCT) has directly compared BRV with ESL, LCM, or PER. To compare BRV with the other add-on AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and tolerability through an adjusted, common-reference based indirect comparison meta-analysis. We systematically searched RCTs in which add-on treatment with ESL or LCM in patients with focal onset seizures have been compared with placebo. Efficacy and tolerability outcomes were considered. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of BRV, LCM, ESL, or PER versus placebo. Adjusted indirect comparisons were then made between BRV and the other three AEDs using the obtained results, comparing the minimum and the highest effective recommended daily dose of each drug. Seventeen RCTs, with a total of 4971 patients were included. After adjusting for dose-effects, indirect comparisons showed no difference between BRV and LCM, ESL, or PER for responder rate and seizure freedom. Lower adverse events were observed with high dose BRV compared to high dose ESL or PER, but no difference was found in withdrawing because of adverse events. Indirect comparisons do not demonstrate a significant difference in efficacy between add-on BRV and LCM, ESL, or PER in focal epilepsy, and might suggest a better tolerability of BRV than ESL, and possibly also PER, at the highest effective recommended dose. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Cosmic Radiation Exposure of Biological Test Systems During the EXPOSE-E Mission

PubMed Central

Hajek, Michael; Bilski, Pawel; Körner, Christine; Vanhavere, Filip; Reitz, Günther

2012-01-01

Abstract In the frame of the EXPOSE-E mission on the Columbus external payload facility EuTEF on board the International Space Station, passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located either as stacks next to biological specimens to determine the depth dose distribution or beneath the sample carriers to determine the dose levels for maximum shielding. The maximum mission dose measured in the upper layer of the depth dose part of the experiment amounted to 238±10 mGy, which relates to an average dose rate of 408±16 μGy/d. In these stacks of about 8 mm height, the dose decreased by 5–12% with depth. The maximum dose measured beneath the sample carriers was 215±16 mGy, which amounts to an average dose rate of 368±27 μGy/d. These values are close to those assessed for the interior of the Columbus module and demonstrate the high shielding of the biological experiments within the EXPOSE-E facility. Besides the shielding by the EXPOSE-E hardware itself, additional shielding was experienced by the external structures adjacent to EXPOSE-E, such as EuTEF and Columbus. This led to a dose gradient over the entire exposure area, from 215±16 mGy for the lowest to 121±6 mGy for maximum shielding. Hence, the doses perceived by the biological samples inside EXPOSE-E varied by 70% (from lowest to highest dose). As a consequence of the high shielding, the biological samples were predominantly exposed to galactic cosmic heavy ions, while electrons and a significant fraction of protons of the radiation belts and solar wind did not reach the samples. Key Words: Space radiation—Dosimetry—Passive radiation detectors—Thermoluminescence—EXPOSE-E. Astrobiology 12, 387–392. PMID:22680685

SU-F-T-283: A Novel Device to Enable Portal Dosimetry for Flattening Filter Free Beams

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

Faught, A; Wu, Q; Adamson, J

Purpose: Varian’s electronic portal imaging device (EPID) based portal dosimetry tool is a popular and effective means of performing IMRT QA. EPIDs for older models of the TrueBeam accelerator utilize a 40cmx30cm Image Detection Unit (IDU) that saturates at the center for standard source to imager distances with high dose rate flattening filter free (FFF) beams. This makes portal dosimetry not possible and an alternative means of IMRT QA necessary. We developed a filter that would attenuate the beam to a dose rate measureable by the IDU for portal dosimetry IMRT QA. Methods: Multipurpose 304 stainless steel plates were placedmore » on an accessory tray to attenuate the beam. Profiles of an open field measured on the IDU were acquired with varying number of plates to assess the thickness needed to reduce the maximum dose rates of 6XFFF and 10XFFF beams to measurable levels. A new portal dose image prediction (PDIP) model was commissioned based on open field measurements with plates in position, and a modified beam profile was input to portal dosimetry calibration at the console to empirically correct for attenuation and scatter. The portal dosimetry tool was used to assess agreement between predicted and measured doses for open 25×25cm{sup 2} fields and intensity modulated fields using 6XFFF and 10XFFF beams. Results: Thicknesses of 2.5cm and 3.8cm of steel were required to reduce the highest dose rates to a measureable level for 6XFFF and 10XFFF, respectively. Gamma analysis using a 3%/3mm relative criterion with the filter in place and using the new PDIP model resulted in 98.2% and 93.6% of pixels passing while intensity modulated fields showed passing rates of 98.2% and 99.0%. Conclusion: Use of the filter allows for portal dosimetry to be used for IMRT QA of FFF plans in place of purchasing a second option for IMRT QA.« less

High fidelity, radiation tolerant analog-to-digital converters

NASA Technical Reports Server (NTRS)

Wang, Charles Chang-I (Inventor); Linscott, Ivan Richard (Inventor); Inan, Umran S. (Inventor)

2012-01-01

Techniques for an analog-to-digital converter (ADC) using pipeline architecture includes a linearization technique for a spurious-free dynamic range (SFDR) over 80 deciBels. In some embodiments, sampling rates exceed a megahertz. According to a second approach, a switched-capacitor circuit is configured for correct operation in a high radiation environment. In one embodiment, the combination yields high fidelity ADC (>88 deciBel SFDR) while sampling at 5 megahertz sampling rates and consuming <60 milliWatts. Furthermore, even though it is manufactured in a commercial 0.25-.mu.m CMOS technology (1 .mu.m=12.sup.-6 meters), it maintains this performance in harsh radiation environments. Specifically, the stated performance is sustained through a highest tested 2 megarad(Si) total dose, and the ADC displays no latchup up to a highest tested linear energy transfer of 63 million electron Volts square centimeters per milligram at elevated temperature (131 degrees C.) and supply (2.7 Volts, versus 2.5 Volts nominal).

Effect of Food Waste Co-Digestion on Digestion, Dewatering, and Cake Quality.

PubMed

Higgins, Matthew; Rajagopalan, Ganesh; Miller, Andre; Brown, Jeffrey; Beightol, Steven

2017-01-01

  The objective of this study was to evaluate the effect of food waste addition on anaerobic digestion performance as well as downstream parameters including dewatering, cake quality, and filtrate quality. Laboratory-scale digesters were fed processed food waste at rates of 25%, 45%, and 65% increased chemical oxygen demand (COD) loading rates compared to a control fed only primary and secondary solids. The specific methane yield increased from 370 L CH4/kg VSadded for the control to 410, 440, and 470 L CH4/kg VSadded for the 25, 45, and 65% food waste addition, respectively. The cake solids after dewatering were all higher for the food waste digesters compared to the control, with the highest cake solids being measured for the 45% food-waste loading. Compared to the control digester, the biosolids odorant concentration increased for the lowest dose of food waste. Odorant concentrations were below detection for the highest food waste loading.

Degradation Behaviour of Gamma Irradiated Poly(Acrylic Acid)-graft-Chitosan Superabsorbent Hydrogel

NASA Astrophysics Data System (ADS)

Ria Barleany, Dhena; Ilhami, Alpin; Yusuf Yudanto, Dea; Erizal

2018-03-01

A series of superabsorbent hydrogels were prepared from chitosan and partially neutralized acrylic acid at room temperature by gamma irradiation technique. The effect of irradiation and chitosan addition to the degradation behaviour of polymer were investigated. The gel content, swelling capacity, Equillibrium Degree of Swelling (EDS), Fourier Transform Infra Red (FTIR), and Scanning Electron Microscopy (SEM) study were also performed. Natural degradation in soil and thermal degradation by using of TGA analysis were observed. The variation of chitosan compositions were 0.5, 1, 1.5, and 2 g and the total irradiation doses were 5, 10, 15, and 20 kGy. The highest water capacity of 583.3 g water/g dry hydrogel was resulted from 5 kGy total irradiation dose and 0,5 g addition of chitosan. From the thermal degradation evaluation by using of TGA analysis showed that irradiation dose did not give a significant influence to the degradation rate. The rate of thermal degradation was ranged between 2.42 to 2.55 mg/min. In the natural test of degradation behaviour by using of soil medium, the hydrogel product with chitosan addition was found to have better degradability compared with the poly(acrylic acid) polymer without chitosan.

The assumption of heterogeneous or homogeneous radioactive contamination in soil/sediment: does it matter in terms of the external exposure of fauna?

PubMed

Beaugelin-Seiller, K

2014-12-01

The classical approach to environmental radioprotection is based on the assumption of homogeneously contaminated media. However, in soils and sediments there may be a significant variation of radioactivity with depth. The effect of this heterogeneity was investigated by examining the external exposure of various sediment and soil organisms, and determining the resulting dose rates, assuming a realistic combination of locations and radionuclides. The results were dependent on the exposure situation, i.e., the organism, its location, and the quality and quantity of radionuclides. The dose rates ranged over three orders of magnitude. The assumption of homogeneous contamination was not consistently conservative (if associated with a level of radioactivity averaged over the full thickness of soil or sediment that was sampled). Dose assessment for screening purposes requires consideration of the highest activity concentration measured in a soil/sediment that is considered to be homogeneously contaminated. A more refined assessment (e.g., higher tier of a graded approach) should take into consideration a more realistic contamination profile, and apply different dosimetric approaches. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adverse event reports following yellow fever vaccination, 2007-13.

PubMed

Lindsey, Nicole P; Rabe, Ingrid B; Miller, Elaine R; Fischer, Marc; Staples, J Erin

2016-05-01

Yellow fever (YF) vaccines have been available since the 1930s and are generally considered safe and effective. However, rare reports of serious adverse events (SAE) following vaccination have prompted the Advisory Committee for Immunization Practices to periodically expand the list of conditions considered contraindications and precautions to vaccination. We describe adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2007 through 2013 and calculate age- and sex-specific reporting rates of all SAE, anaphylaxis, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). There were 938 adverse events following YF vaccination reported to VAERS from 2007 through 2013. Of these, 84 (9%) were classified as SAEs for a rate of 3.8 per 100 000 doses distributed. Reporting rates of SAEs increased with increasing age with a rate of 6.5 per 100 000 in persons aged 60-69 years and 10.3 for ≥70 years. The reporting rate for anaphylaxis was 1.3 per 100 000 doses distributed and was highest in persons ≤18 years (2.7 per 100 000). Reporting rates of YEL-AND and YEL-AVD were 0.8 and 0.3 per 100 000 doses distributed, respectively; both rates increased with increasing age. These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of continued physician and traveller education regarding the risks and benefits of YF vaccination, particularly for older travellers. Published by Oxford University Press on behalf of the International Society of Travel Medicine, 2016. This work is written by US Government employees and is in the public domain in the United States.

A novel approach to reducing admissions for children with sickle cell disease in pain crisis through individualization and standardization in the emergency department.

PubMed

Schefft, Matthew R; Swaffar, Caitlan; Newlin, Jennifer; Noda, Cady; Sisler, India

2018-06-01

Vaso-occlusive crisis (VOC) is frequent in children with sickle cell disease (SCD) creating significant burden on patients, families, and emergency departments (ED). The objective of the project was to reduce the admission rate for children with SCD presenting to our ED with VOC by >20% within 6 months of initiating individualized pain plans (IPP). A multi-disciplinary quality improvement team was assembled. A Plan-Do-Study-Act (PDSA) format was employed. The IPP document was created in a unique folder within the electronic medical record. IPPs were created through retrospective chart review for our 80 highest resource users. Pediatric residents, ED residents, and ED attending physicians were instructed on use of the IPPs. Our study measured the presence of an IPP, adherence to the IPP, and time to opiate administration. Our primary outcome was admission rate. Length of stay and 72-hr return to the ED were assessed as balancing measures. Overall, admission rate decreased by 24% following implementation compared with the previous 5 years (P = 0.046). IPPs were created for 78% of patients and followed by ED staff in 86% of visits. Admission rate was significantly lower for patients receiving a second opiate dose within 45 min of the first dose (P < 0.01). There was no difference in readmission rate or 72-hr return rate to ED. This study presents an effective strategy to reduce admission rate for children with SCD presenting with VOC. Shorter time to second opiate dosing was also associated with reduced risk of admission. © 2018 Wiley Periodicals, Inc.

Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecate (Mustela eversmanni)

USGS Publications Warehouse

Wimsatt, Jeffrey; Biggins, Dean E.; Innes, Kim; Taylor, Bobbi; Garell, Della

2003-01-01

We assessed the safety and efficacy of an experimental canarypox-vectored recombinant canine distemper virus (CDV) subunit vaccine in the Siberian polecat (Mustela eversmanni), a close relative of the black-footed ferret, (M. nigripes), an endangered species that is highly susceptible to the virus. Siberian polecats were randomized into six treatment groups. Recombinant canine distemper vaccine was administered s.c. at three dose levels (104.5, 105.0, and 105.5 plaque-forming units [PFU] per dose) and was administered orally by spraying the vaccine into the oropharnyx at two dose levels (105.5, 108.0 PFU per dose). The sixth group of control animals was not vaccinated. For both routes of administration, two 1-ml doses of reconstituted vaccine were delivered 4 wk apart, followed by live virus challenge 3 wk after the second vaccination. During the challenge, Synder Hill test strain CDV obtained from the National Veterinary Services Laboratory in Ames, Iowa, was administered i.p. Serial blood samples for CDV serology were collected immediately before vaccination and challenge, and 10, 15, and 20 days after challenge. Clinical signs and body weights were recorded up to 32 days after challenge. The survival rate in animals receiving vaccine at the highest oral dose (108.0 PFU per dose) was 83.3%. Survival rate was 50.0% in the high s.c. and 60.0% in the medium s.c. groups. All animals in the low–s.c. dose, low–oral dose, and control groups died after exposure. Vaccine dose overall (oral and s.c.) and dose in response to s.c. administration when considered alone were significant predictors of survival (P = 0.006 and P = 0.04, respectively). Among the polecats challenged with virulent virus, those that died became sick sooner than those that survived. Animals that died lost significantly more weight during the 10 days after challenge than did animals that survived (P = 0.02). Survival rates did not differ by sex, founder female status, or breeding pedigree in any of the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers (P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.

Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecat (Mustela eversmanni).

PubMed

Wimsatt, Jeffrey; Biggins, Dean; Innes, Kim; Taylor, Bobbi; Garell, Della

2003-03-01

We assessed the safety and efficacy of an experimental canarypox-vectored recombinant canine distemper virus (CDV) subunit vaccine in the Siberian polecat (Mustela eversmanni), a close relative of the black-footed ferret, (M. nigripes), an endangered species that is highly susceptible to the virus. Siberian polecats were randomized into six treatment groups. Recombinant canine distemper vaccine was administered s.c. at three dose levels (10(4.5), 10(5.0), and 10(5.5) plaque-forming units [PFU] per dose) and was administered orally by spraying the vaccine into the oropharnyx at two dose levels (10(5.5), 10(8.0) PFU per dose). The sixth group of control animals was not vaccinated. For both routes of administration, two 1-ml doses of reconstituted vaccine were delivered 4 wk apart, followed by live virus challenge 3 wk after the second vaccination. During the challenge, Synder Hill test strain CDV obtained from the National Veterinary Services Laboratory in Ames, Iowa, was administered i.p. Serial blood samples for CDV serology were collected immediately before vaccination and challenge, and 10, 15, and 20 days after challenge. Clinical signs and body weights were recorded up to 32 days after challenge. The survival rate in animals receiving vaccine at the highest oral dose (10(8.0) PFU per dose) was 83.3%. Survival rate was 50.0% in the high s.c. and 60.0% in the medium s.c. groups. All animals in the low-s.c. dose, low-oral dose, and control groups died after exposure. Vaccine dose overall (oral and s.c.) and dose in response to s.c. administration when considered alone were significant predictors of survival (P = 0.006 and P = 0.04, respectively). Among the polecats challenged with virulent virus, those that died became sick sooner than those that survived. Animals that died lost significantly more weight during the 10 days after challenge than did animals that survived (P = 0.02). Survival rates did not differ by sex, founder female status, or breeding pedigree in any of the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers (P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.

Systemic Effects of Intracoronary Nitroglycerin during Coronary Angiography in Children after Heart Transplantation

PubMed Central

Lara, Diego A.; Olive, Mary K.; George, James F.; Brown, Robert N.; Carlo, Waldemar F.; Colvin, Edward V.; Steenwyck, Brad L.

2014-01-01

Coronary spasm during coronary angiography for vasculopathy in children can be prevented by the intracoronary administration of nitroglycerin. We reviewed the anesthesia and catheterization reports and charts for pediatric transplant recipients who underwent angiography from 2005 through 2010. Correlation analysis was used to study the relation of post-injection systolic blood pressure (SBP) to nitroglycerin dose. Forty-one angiographic evaluations were performed on 25 patients (13 male and 12 female). Mean age was 9.9 ± 3.2 years (range, 3.3–16.1 yr). The mean total dose of nitroglycerin was 2.93 ± 1.60 µg/kg (range, 1–8 µg/kg). There was a significant drop between the baseline SBP (mean, 106 ± 21.6 mmHg) and the lowest mean SBP before nitroglycerin administration (78 ± 13.2, P <0.0001, paired t test). There was no significant additional change in SBP (mean after nitroglycerin administration, 80.7 ± 13.1 mmHg; P = 0.2). There was a significant drop in lowest heart rate between baseline (109 ± 16.5 beats/min) and before nitroglycerin administration (89 ± 14.3 beats/min; P <0.0001, paired t test). There was no significant additional change in heart rate (mean heart rate after nitroglycerin, 84 ± 17.7 beats/min; P = 0.09). There were 2 interventions for SBP before nitroglycerin and 2 after nitroglycerin. One child experienced a transient ST-T–segment change during angiography after nitroglycerin. In the highest dose range, the additional decrease in SBP was 7.2 mmHg (P=0.03). Routine intracoronary nitroglycerin administration in this dose range produced no significant changes in SBP or heart rate in children. PMID:24512395

Systemic effects of intracoronary nitroglycerin during coronary angiography in children after heart transplantation.

PubMed

Lara, Diego A; Olive, Mary K; George, James F; Brown, Robert N; Carlo, Waldemar F; Colvin, Edward V; Steenwyck, Brad L; Pearce, F Bennett

2014-02-01

Coronary spasm during coronary angiography for vasculopathy in children can be prevented by the intracoronary administration of nitroglycerin. We reviewed the anesthesia and catheterization reports and charts for pediatric transplant recipients who underwent angiography from 2005 through 2010. Correlation analysis was used to study the relation of post-injection systolic blood pressure (SBP) to nitroglycerin dose. Forty-one angiographic evaluations were performed on 25 patients (13 male and 12 female). Mean age was 9.9 ± 3.2 years (range, 3.3-16.1 yr). The mean total dose of nitroglycerin was 2.93 ± 1.60 µg/kg (range, 1-8 µg/kg). There was a significant drop between the baseline SBP (mean, 106 ± 21.6 mmHg) and the lowest mean SBP before nitroglycerin administration (78 ± 13.2, P <0.0001, paired t test). There was no significant additional change in SBP (mean after nitroglycerin administration, 80.7 ± 13.1 mmHg; P = 0.2). There was a significant drop in lowest heart rate between baseline (109 ± 16.5 beats/min) and before nitroglycerin administration (89 ± 14.3 beats/min; P <0.0001, paired t test). There was no significant additional change in heart rate (mean heart rate after nitroglycerin, 84 ± 17.7 beats/min; P = 0.09). There were 2 interventions for SBP before nitroglycerin and 2 after nitroglycerin. One child experienced a transient ST-T-segment change during angiography after nitroglycerin. In the highest dose range, the additional decrease in SBP was 7.2 mmHg (P=0.03). Routine intracoronary nitroglycerin administration in this dose range produced no significant changes in SBP or heart rate in children.

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

PubMed Central

Haney, Margaret; Malcolm, Robert J; Babalonis, Shanna; Nuzzo, Paul A; Cooper, Ziva D; Bedi, Gillinder; Gray, Kevin M; McRae-Clark, Aimee; Lofwall, Michelle R; Sparenborg, Steven; Walsh, Sharon L

2016-01-01

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ9-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30–5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n=31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n=8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of ‘High', ‘Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis. PMID:26708108

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis.

PubMed

Haney, Margaret; Malcolm, Robert J; Babalonis, Shanna; Nuzzo, Paul A; Cooper, Ziva D; Bedi, Gillinder; Gray, Kevin M; McRae-Clark, Aimee; Lofwall, Michelle R; Sparenborg, Steven; Walsh, Sharon L

2016-07-01

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ(9)-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30-5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n=31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n=8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of 'High', 'Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis.

Lead accumulation in feathers of nestling black-crowned night herons (Nycticorax nycticorax) experimentally treated in the field.

PubMed

Golden, Nancy H; Rattner, Barnett A; Cohen, Jonathan B; Hoffman, David J; Russek-Cohen, Estelle; Ottinger, Mary Ann

2003-07-01

Although lead can attain high concentrations in feathers, interpretation of the biological significance of this phenomenon is difficult. As part of an effort to develop and validate noninvasive methods to monitor contaminant exposure in free-ranging birds, lead uptake by feathers of nestling black-crowned night herons (Nycticorax nycticorax) was evaluated in a controlled exposure study. Four- to 6-d-old heron nestlings (one/nest) at Chincoteague Bay, Virginia (USA), received a single intraperitoneal injection of dosing vehicle (control, n = 7) or a dose of lead nitrate in water (0.01, 0.05, or 0.25 mg Pb/g body wt of nestling; n = 6 or 7/dose) chosen to yield feather lead concentrations found at low- to moderately polluted sites. Nestlings were euthanized at 15 d of age. Lead accumulation in feathers was associated with concentrations in bone, kidney, and liver (r = 0.32-0.74, p < 0.02) but exhibited only modest dose dependence. Blood delta-aminolevulinic acid dehydratase activity was inhibited by lead, although effects on other biochemical endpoints were marginal. Tarsus growth rate was inversely related to feather lead concentration. Culmen growth rate was depressed in nestlings treated with the highest dose of lead but not correlated with feather lead concentration. These findings provide evidence that feathers of nestling herons are a sensitive indicator of lead exposure and have potential application for the extrapolation of lead concentrations in other tissues and the estimation of environmental lead exposure in birds.

Lead accumulation in feathers of nestling black-crowned night-herons (Nycticorax nycticorax) experimentally treated in the field

USGS Publications Warehouse

Golden, N.H.; Rattner, B.A.; Cohen, J.B.; Hoffman, D.J.; Russek-Cohen, E.; Ottinger, M.A.

2003-01-01

Although lead can attain high concentrations in feathers, interpretation of the biological significance of this phenomenon is difficult. As part of an effort to develop and validate non-invasive methods to monitor contaminant exposure in free-ranging birds, lead uptake by feathers of nestling black-crowned night-herons (Nycticorax nycticorax) was evaluated in a controlled exposure study. Four to six day-old heron nestlings (one/nest) at Chincoteague Bay, Virginia, received a single intraperitoneal injection of dosing vehicle (control; n=7) or a dose of lead nitrate in water (0.01, 0.05, or 0.25 mg Pb/g body weight of nestling; n=6 or 7/dose) chosen to yield feather lead concentrations found at low to moderately polluted sites. Nestlings were euthanized at 15 days of age. Lead accumulation in feathers was associated with concentrations in bone, kidney, and liver (r = 0.32 - 0.74, p < 0.02), but exhibited only modest dose-dependence. Blood delta-aminolevulinic acid dehydratase activity was inhibited by lead, although effects on other biochemical endpoints were marginal. Tarsus growth rate was inversely related to feather lead concentration. Culmen growth rate was depressed in nestlings treated with the highest dose of lead, but not correlated with feather lead concentration. These findings provide evidence that feathers of nestling herons are a sensitive indicator of lead exposure and have potential application for the extrapolation of lead concentrations in other tissues and the estimation of environmental lead exposure in birds.

Fine and ultrafine particle doses in the respiratory tract from digital printing operations.

PubMed

Voliotis, Aristeidis; Karali, Irene; Kouras, Athanasios; Samara, Constantini

2017-01-01

In this study, we report for the first time particle number doses in different parts of the human respiratory tract and real-time deposition rates for particles in the 10 nm to 10 μm size range emitted by digital printing operations. Particle number concentrations (PNCs) and size distribution were measured in a typical small-sized printing house using a NanoScan scanning mobility particle sizer and an optical particle sizer. Particle doses in human lung were estimated applying a multiple-path particle dosimetry model under two different breathing scenarios. PNC was dominated by the ultrafine particle fractions (UFPs, i.e., particles smaller than 100 nm) exhibiting almost nine times higher levels in comparison to the background values. The average deposition rate fοr each scenario in the whole lung was estimated at 2.0 and 2.9 × 10 7 particles min -1 , while the respective highest particle dose in the tracheobronchial tree (2.0 and 2.9 × 10 9 particles) was found for diameter of 50 nm. The majority of particles appeared to deposit in the acinar region and most of them were in the UFP size range. For both scenarios, the maximum deposition density (9.5 × 10 7 and 1.5 × 10 8 particles cm -2 ) was observed at the lobar bronchi. Overall, the differences in the estimated particle doses between the two scenarios were 30-40% for both size ranges.

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

PubMed Central

Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Graña, Maria Gabriela; Heijnen, Esther; Smolenov, Igor; Dull, Peter M

2015-01-01

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885] PMID:25969894

Proton irradiation damage of an annealed Alloy 718 beam window

DOE PAGES

Bach, H. T.; Anderoglu, O.; Saleh, T. A.; ...

2015-04-01

Mechanical testing and microstructural analysis was performed on an Alloy 718 window that was in use at the Los Alamos Neutron Science Center (LANSCE) Isotope Production Facility (IPF) for approximately 5 years. It was replaced as part of the IPF preventive maintenance program. The window was transported to the Wing 9 hot cells at the Chemical and Metallurgical Research (CMR) LANL facility, visually inspected and 3-mm diameter samples were trepanned from the window for mechanical testing and microstructural analysis. Shear punch testing and optical metallography was performed at the CMR hot cells. The 1-mm diameter shear punch disks were cutmore » into smaller samples to further reduce radiation exposure dose rate using Focus Ion Beam (FIB) and microstructure changes were analyzed using a Transmission Electron Microscopy (TEM). Irradiation doses were determined to be ~0.2–0.7 dpa (edge) to 11.3 dpa (peak of beam intensity) using autoradiography and MCNPX calculations. The corresponding irradiation temperatures were calculated to be ~34–120 °C with short excursion to be ~47–220 °C using ANSYS. Mechanical properties and microstructure analysis results with respect to calculated dpa and temperatures show that significant work hardening occurs but useful ductility still remains. The hardening in the lowest dose region (~0.2–0.7 dpa) was the highest and attributed to the formation of γ" precipitates and irradiation defect clusters/bubbles whereas the hardening in the highest dose region (~11.3 dpa) was lower and attributed mainly to irradiation defect clusters and some thermal annealing.« less

Cancer mortality risk among military participants of a 1958 atmospheric nuclear weapons test.

PubMed Central

Watanabe, K K; Kang, H K; Dalager, N A

1995-01-01

OBJECTIVES. This study was undertaken to determine if Navy veterans who participated in an atmospheric nuclear test in 1958 were at increased risk of death from certain cancers. METHODS. Cancer mortality risk of 8554 Navy veterans who participated in an atmospheric nuclear test in the Pacific was compared with that of 14,625 Navy veterans who did not participate in any test. Radiation dosage information was obtained from film badges for 88% of the test participants. RESULTS. The median radiation dose for the test participants was 388 mrem (3.88 millisieverts [mSv]). Among participants who received the highest radiation dose (> 1000 mrem, or 10 mSv), an increased mortality risk for all causes (relative risk [RR] = 1.23; 95% confidence interval [CI] = 1.04, 1.45), all cancers (RR = 1.42; 95% CI = 1.03, 1.96), and liver cancer (RR = 6.42; 95% CI = 1.17, 35.3) was observed. The risk for cancer of the digestive organs was elevated among test participants (rate ratio = 1.47; 95% CI = 1.06, 2.04) but with no significant dose-response trend. Many of the cancers of a priori interest were not significantly elevated in the overall test participant group or in the group that received the highest radiation dose. CONCLUSIONS. Most of the cancers suspected of being radiogenic were not significantly elevated among the test participants. Nevertheless, increased risks for certain cancers cannot be ruled out at this time. Veterans who participated in the nuclear weapons tests should continue to be monitored. PMID:7702116

Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: a review

PubMed Central

Kurz, A; Farlow, M; Lefèvre, G

2009-01-01

Background: Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer’s disease (AD) (including the USA, Latin America, Europe and Asia). Objectives: To review the available pharmacokinetic data that supported the rationale behind the development of the rivastigmine transdermal patch and its clinical effects in dementia therapy. This article will also discuss how the patch may alter the treatment paradigm for patients with AD. Results: The 9.5 mg/24 h rivastigmine patch was shown to provide comparable exposure to the highest recommended doses of capsules (12 mg/day) with significantly lower maximum plasma concentration (Cmax 8.7 vs. 21.6 ng/ml) and slower absorption rate (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated into similar efficacy with three times fewer reports of nausea and vomiting (7.2% vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the 9.5 mg/24 h patch group achieved their target therapeutic dose at the end of the study, compared with those in the 12 mg/day capsule group (95.9% vs. 64.4%). Conclusion: The rivastigmine patch provides continuous drug delivery over 24 h and similar efficacy to the highest recommended dose of oral rivastigmine with improved tolerability. This may allow patients to achieve optimal therapeutic doses and to benefit from a longer duration of treatment. PMID:19392927

Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) n.e. Brown.

PubMed

do Vale, T Gurgel; Furtado, E Couto; Santos, J G; Viana, G S B

2002-12-01

Citral, myrcene and limonene (100 and 200 mg/kg body wt., i.p.), constituents of essential oils from Lippia alba chemotypes, decreased not only the number of crossings but also numbers for rearing and grooming, as measured by the open-field test in mice. Although muscle relaxation detected by the rota rod test was seen only at the highest doses of citral (200 mg/kg body wt.) and myrcene (100 and 200 mg/kg body wt.), this effect was observed even at the lowest dose of limonene (50 mg/kg body wt.). Also, citral and myrcene (100 and 200 mg/kg body wt.) increased barbiturate sleeping time as compared to control. Limonene was also effective at the highest dose, and although citral did not increase the onset of sleep, it increased the duration of sleep, which is indicative of a potentiation of sleeping time. Citral (100 and 200 mg/kg body wt.) increased 2.3 and 3.5 times, respectively, the barbiturate sleeping time in mice. Similar effects were observed for myrcene and limonene at the highest dose (200 mg/kg body wt.) which increased the sleeping time around 2.6 times. In the elevated-plus maze, no effect was detected with citral up to 25 mg/kg body wt., while at a high dose it decreased by 46% the number of entries in the open arms. A smaller but significant effect was detected with limonene (5 mg/kg body wt.). While myrcene (10 mg/kg body wt.) decreased only by 22% the number of entries in the open arms, this parameter was decreased by 48% at the highest dose. Our study showed that citral, limonene and myrcene presented sedative as well as motor relaxant effects. Although only at the highest dose, they also produced a potentiation of the pentobarbital-induced sleeping time in mice, which was more intense in the presence of citral. In addition, neither of them showed an anxiolytic effect, but rather a slight anxiogenic type of effect at the higher doses.

Study Of Dose Distribution In A Human Body In Space Flight With The Spherical Tissue-Equivalent Phantom

NASA Astrophysics Data System (ADS)

Shurshakov, Vyacheslav; Akatov, Yu; Petrov, V.; Kartsev, I.; Polenov, Boris; Petrov, V.; Lyagushin, V.

In the space experiment MATROSHKA-R, the spherical tissue equivalent phantom (30 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been installed in the star board crew cabin of the ISS Service Module. Due to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a real human body. If compared with the anthropomorphic phantom Rando used inside and outside the ISS, the spherical phantom has lower mass, smaller size, and requires less crew time for the detector retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. In the first phase of the experiment the dose measurements were realized with only passive detectors (thermoluminescent and solid state track detectors). There were two experimental sessions with the spherical phantom in the crew cabin, (1) from Jan. 29, 2004 to Apr. 30, 2004 and (2) from Aug. 11, 2004 to Oct. 10, 2005. The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. The results obtained with the passive detectors returned to the ground after each session show the dose difference on the phantom surface as much as a factor of 2, the highest dose being observed close to the outer wall of the crew cabin, and the lowest dose being in the opposite location along the phantom diameter. Maximum dose rate measured in the phantom (0.31 mGy/day) is obviously due to the galactic cosmic ray (GCR) and Earth' radiation belt contribution on the ISS trajectory. Minimum dose rate (0.15 mGy/day) is caused mainly by the strongly penetrating GCR particles and is observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the crew cabin are also estimated with the spherical phantom. The estimated effective dose rate (about 0.49 mSv/day at radiation quality factor of 2.6) is from 12 to 15 per cent lower than the averaged dose on the phantom surface as dependent on the body attitude.

TH-AB-207A-04: Assessment of Patients’ Cumulative Effective Dose From CT Examinations

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

Bostani, M; Cagnon, C; Sepahdari, A

Purpose: The Joint Commission requires institutions to consider patient’s age and recent imaging exams when deciding on the most appropriate type of imaging exam. Additionally, knowing patient’s imaging history can help prevent duplicate scans. Radiation dose management software affords new opportunities to identify and utilize patients with high cumulative doses as one proxy for subsequent review of imaging history and opportunities in avoiding redundant exams. Methods: Using dose management software (Radimetrics, Bayer Healthcare) a total of 72073 CT examinations performed from Jan 2015 to Jan 2016 were examined to categorize patients with a cumulative effective dose of 100 mSv andmore » above. This threshold was selected based on epidemiological studies on populations exposed to radiation, which demonstrate a statistical increase of cancer risk at doses above 100 mSv. Histories of patients with highest cumulative dose and highest number of exams were further investigated by a Radiologist for appropriateness of recurrent studies and potential opportunities for reduction. Results: Out of 34762 patients, 927 (2.7%) were identified with a cumulative dose of 100 mSv and above. The highest cumulative dose (842 mSv) belonged to an oncology patient who underwent 2 diagnostic exams and 9 interventional ablative CT guided procedures. The patient with highest number of exams (56 counts) and cumulative dose of 170 mSv was a 17 year old trauma patient. An imaging history review of these two patients did not suggest any superfluous scans. Conclusion: Our limited pilot study suggests that recurrent CT exams for patients with oncologic or severe trauma history may be warranted and appropriate. As a result, for future studies we will be focusing on high dose patient cohorts not associated with oncology or severe trauma. Additionally, the review process itself has suggested areas for potential improvement in patient care, including improved documentation and Radiologist involvement in patient management. Dr. McNitt-Gray’s disclosures: Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Effects of T-2 Toxin on Pacific White Shrimp Litopenaeus vannamei: Growth, and Antioxidant Defenses and Capacity and Histopathology in the Hepatopancreas.

PubMed

Deng, Yijia; Wang, Yaling; Zhang, Xiaodi; Sun, Lijun; Wu, Chaojin; Shi, Qi; Wang, Rundong; Sun, Xiaodong; Bi, Siyuan; Gooneratne, Ravi

2017-03-01

Modified-masked T-2 toxin (mT-2) formed during metabolism in edible aquatic animals may go undetected by traditional analytical methods, thereby underestimating T-2 toxicity. The effects of T-2 on growth and antioxidant capacity and histopathological changes in the hepatopancreas were studied in Pacific white shrimp Litopenaeus vannamei exposed for 20 d to 0, 0.5, 1.2, 2.4, 4.8, and 12.2 mg/kg of T-2 in their feed. The concentration of mT-2 in the hepatopancreas was detected by liquid chromatography-tandem mass spectrophotometry before and after trifluoroacetic acid (TFA) treatment that converted mT-2 to free T-2. A dose-dependent increase in mT-2 concentration was observed in the hepatopancreas. Dietary exposure to T-2 significantly decreased (P < 0.05) shrimp growth and survival rate compared with the controls. The malondialdehyde (MDA) concentration was significantly increased in shrimp exposed to feed with ≥2.4 mg/kg T-2 (P < 0.05). The antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx), total antioxidant capacity (T-AOC), and also glutathione (GSH) content increased in shrimp dosed with 2.4-4.8 mg/kg T-2 but declined at the highest dose (12.2 mg/kg), probably indicating an inability to cope with high concentrations of reactive oxygen species (ROS) as evident from a marked increase in MDA (P < 0.05) culminating in cellular toxicity. Histopathological changes in the hepatopancreas were dose dependent, with cell autophagy evident at the highest exposure dose. This is the first report in shrimp of a dose-dependent increase in ROS, SOD enzyme activity, and T-AOC at low T-2 exposures, and associated histopathological changes in the hepatopancreas, in response to dietary T-2. Received January 26, 2016; accepted October 9, 2016.

Exposure to fine particulate, black carbon, and particle number concentration in transportation microenvironments

NASA Astrophysics Data System (ADS)

Morales Betancourt, R.; Galvis, B.; Balachandran, S.; Ramos-Bonilla, J. P.; Sarmiento, O. L.; Gallo-Murcia, S. M.; Contreras, Y.

2017-05-01

This research determined intake dose of fine particulate matter (PM2.5), equivalent black carbon (eBC), and number of sub-micron particles (Np) for commuters in Bogotá, Colombia. Doses were estimated through measurements of exposure concentration, a surrogate of physical activity, as well as travel times and speeds. Impacts of travel mode, traffic load, and street configuration on dose and exposure were explored. Three road segments were selected because of their different traffic loads and composition, and dissimilar street configuration. The transport modes considered include active modes (walking and cycling) and motorized modes (bus, car, taxi, and motorcycle). Measurements were performed simultaneously in the available modes at each road segment. High average eBC concentrations were observed throughout the campaign, ranging from 20 to 120 μgm-3 . Commuters in motorized modes experienced significantly higher exposure concentrations than pedestrians and bicyclists. The highest average concentrations of PM2.5, eBC , and Np were measured inside the city's Bus Rapid Transit (BRT) system vehicles. Pedestrians and bicycle users in an open street configuration were exposed to the lowest average concentrations of PM2.5 and eBC , six times lower than those experienced by commuters using the BRT in the same street segment. Pedestrians experienced the highest particulate matter intake dose in the road segments studied, despite being exposed to lower concentrations than commuters in motorized modes. Average potential dose of PM2.5 and eBC per unit length traveled were nearly three times higher for pedestrians in a street canyon configuration compared to commuters in public transport. Slower travel speed and elevated inhalation rates dominate PM dose for pedestrians. The presence of dedicated bike lanes on sidewalks has a significant impact on reducing the exposure concentration for bicyclists compared to those riding in mixed traffic lanes. This study proposes a simple method to perform loading effect correction for measurements of black carbon using multiple portable aethalometers.

Clinical and pharmacokinetic results with a new ultrashort-acting calcium antagonist, clevidipine, following gradually increasing intravenous doses to healthy volunteers

PubMed Central

Ericsson, H; Fakt, C; Jolin-Mellgård, Å; Nordlander, M; Sohtell, L; Sunzel, M; Regårdh, C G

1999-01-01

Aims To investigate the tolerability and safety of clevidipine in healthy male volunteers during intravenous infusion at gradually increasing dose rates and to obtain preliminary information on the pharmacokinetics and pharmacodynamic effects of the drug. Methods Twenty-five subjects were enrolled in the study and twenty-one of them were included twice, resulting in a total of forty-six study entries encompassing 20 min infusions of clevidipine at target dose rates ranging from 0.12 to 48 nmol min−1 kg−1. Haemodynamic variables and adverse events were recorded throughout the study. Concentrations of clevidipine and its primary metabolite, H 152/81, were followed in whole blood, and the pharmacokinetics were evaluated by non-compartmental and compartmental analysis. An Emax model was fitted to the effect on mean arterial pressure (MAP) over heart rate (HR) and the corresponding blood concentrations of clevidipine. Results Clevidipine was administered up to a target dose rate of 48 nmol min−1 kg−1, where a pre-determined escape criterion was reached (HR>120 beats min−1) and the study was stopped. The most common adverse events were flush and headache, which can be directly related to the mechanism of action of clevidipine. There was a linear relationship between blood concentration and dose rate in the range studied. The median clearance value determined by non-compartmental analysis was 0.125 l min−1 kg−1. Applying the population approach to the sparse data on clevidipine concentrations, an open two compartment pharmacokinetic model was found to be the best model in describing the disposition of the drug. The population mean clearance value determined by this method was 0.121 l min−1 kg−1, and the volume of distribution at steady state was 0.56 l kg−1. The initial half-life, contributing by more than 80% to the total area under the blood concentration-time curve following i.v. bolus administration, was 1.8 min, and the terminal half-life was 9.5 min. At the highest dose rates, MAP was reduced by approximately 10%, and the HR reached the pre-determined escape criterion for this study (>120 beats min−1). Conclusions Clevidipine is well tolerated and safe in healthy volunteers at dose rates up to at least 48 nmol min−1 kg−1. The pharmacokinetics are linear over a wide dose range. Clevidipine is a high clearance drug with extremely short half-lives. The effect of clevidipine on the blood pressure was marginal, probably due to a compensatory baroreflex activation in this population of healthy volunteers. A simple Emax model adequately describes the relationship between the pharmacodynamic response (MAP/HR) and the blood concentrations of clevidipine. PMID:10336577

Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer

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

Yamada, Shigeru, E-mail: s_yamada@nirs.go.jp; Kamada, Tadashi; Ebner, Daniel K.

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer. Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction. Results: Duringmore » phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively. Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery.« less

Effects of arbuscular mycorrhizal inoculation and fertilization on mycorrhizal Statute of Jacaranda mimosifolia D.Don cultivated in nurseries.

PubMed

Zaouchi, Yousr; Bahri, Nada Ben; Rezgui, S; Bettaieb, Taoufik

2013-10-01

The effects of fertilization and the nature of the inoculum as well as the variation of the dose intake of the latter on the level of Jacaranda mimosifolia D.Don mycorhization were tested. Young plants were treated with two inoculums presenting different origins, compositions and modes of application: one is a commercial product containing Glomus irregulare, and the other is a composite indigenous inoculum resulting from trapping five species of genus Glomus and also from multiplication on mycotrophic plants: leek (Allium porrum L.) and vetch (Vicia sativa L.). For each inoculum, two doses were tested and for each dose of inoculum, four levels of fertilization based on a complete commercial fertilizer (Osmocote) were tested: 0 g/plant, 2 g/plant, 4 g/plant, and 6g/plant. Three repetitions were performed for each combination treatment of inoculum/fertilizer. One-year-old young Jacaranda plants, being about 40 cm high, were cultured under greenhouse in 10/12 cm caliber pots. After six months, all the inoculated plants were mycorrhized. According to endomycorrhizal structures found on their roots, plants receiving doses of composite indigenous inoculum reached a more advanced stage of mycorrhization than those treated with the commercial inoculum. The existence of an interaction effect between the inoculum dose and the level of fertilization on Jacaranda mycorhization rate was excluded. These two parameters of variation were studied as simple effects. The increase in commercial inoculum dose had a significant positive influence on the level of Jacaranda plants mycorrhization (P=0.05). The rate of mycorrhization jumped from 12.69% to 21.92%. Nonetheless, for plants receiving increasing doses of composite indigenous inoculum, the level of mycorrhization has varied randomly. In both instances of inoculum treatments, increasing the dose of fertilizer significantly inhibited endomycorrhizal colonization of Jacaranda roots (P=0.01). Thus, the rate of root colonization decreased from 47.43% to 2.41% for plants receiving the composite indigenous inoculums. It decreased from 32.35% to 3.95% for those treated with the commercial inoculum. Mycorrhization had a positive effect on root dry biomass of Jacaranda, as in the case of unfertilize ave the highest rates of colonization. Copyright © 2013. Published by Elsevier SAS.

High-Risk Prescribing to Medicaid Enrollees Receiving Opioid Analgesics: Individual- and County-Level Factors.

PubMed

Heins, Sara E; Sorbero, Mark J; Jones, Christopher M; Dick, Andrew W; Stein, Bradley D

2018-01-05

Prescription opioid overdoses have increased dramatically in recent years, with the highest rates among Medicaid enrollees. High-risk prescribing includes practices associated with overdoses and a range of additional opioid-related problems. To identify individual- and county-level factors associated with high-risk prescribing among Medicaid enrollees receiving opioids. In a four-states, cross-sectional claims data study, Medicaid enrollees 18-64 years old with a new opioid analgesic treatment episode 2007-2009 were identified. Multivariate regression analyses were conducted to identify factors associated with high-risk prescribing, defined as high-dose opioid prescribing (morphine equivalent daily dose ≥100 mg for >6 days), opioid overlap, opioid-benzodiazepine overlap. High-risk prescribing occurred in 39.4% of episodes. Older age, rural county of residence, white race, and major depression diagnosis were associated with higher rates of all types of high-risk prescribing. Individuals with prior opioid, alcohol, and hypnotic/sedative use disorder diagnoses had lower odds of high-dose opioid prescribing but higher odds of opioid overlap and opioid-benzodiazepine overlap than individuals without such disorders. High-dose opioid prescribing in Massachusetts was less common than in California, Illinois, and New York, whereas the rate of benzodiazepine overlap in Massachusetts was more common than in other states. Conclusions/Importance: High-risk prescribing was common and associated with several important demographic, clinical, and community factors. Findings can be used to inform targeted interventions designed to reduce such prescribing, and given state variation observed, further research is needed to better understand the effects of state policies on high-risk prescribing.

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation.

PubMed

Fabi, Alessandra; Metro, Giulio; Russillo, Michelangelo; Vidiri, Antonello; Carapella, Carmine Maria; Maschio, Marta; Cognetti, Francesco; Jandolo, Bruno; Mirri, Maria Alessandra; Sperduti, Isabella; Telera, Stefano; Carosi, Mariantonia; Pace, Andrea

2009-03-31

In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m(2) weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting. 40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m(2) to 100 mg/m(2). Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients. Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine. Low-dose fotemustine at 65-75 mg/m(2) (induction phase) followed by 75-85 mg/m(2) (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.

Solid state radiolysis of amino acids in an astrochemical perspective

NASA Astrophysics Data System (ADS)

Cataldo, Franco; Angelini, Giancarlo; Iglesias-Groth, Susana; Manchado, Arturo

2011-01-01

The aliphatic amino acids L-alanine and L-leucine and the aromatic amino acids L-phenylalanine, L-tyrosine and L-tryptophan were irradiated in the solid state to a dose of 3.2 MGy. The degree of decomposition was measured by differential scanning calorimetry (DSC). Furthermore the degree of radioracemization was measured by optical rotatory dispersion (ORD) spectroscopy. From the DSC measurement a radiolysis rate constant k and the half life T1/2 for each amino acid have been determined and extrapolated to a dose of 14 MGy, which corresponds to the expected total dose delivered by the decay of radionuclides to the organic molecules present in comets and asteroids in 4.6×109 years, the age of the Solar System. It is shown that all the amino acids studied can survive a radiation dose of 14 MGy although they are reduced to 1/4-1/5 of their original value they had at the beginning of the history of the Solar System. Consequently, the amount of alanine or leucine found today in the meteorites known as carbonaceous chondrites is just 1/4-1/5 of the amount originally present at the epoch of the formation of the Solar System 4.6×109 years ago. Among the amino acids studied, tyrosine shows the highest radiation resistance while tryptophan does not combine its relatively high radiation resistance with an elevated level of radioracemization resistance. Apart from the exception of tryptophan, it is shown that the radiolysis rate constants k of all the amino acids studied are in reasonable agreement with the radioracemization rate constant krac.

Cadmium induced changes in Solidago chilensis Meyen (Asteraceae) grown on organically fertilized soil with reference to mycorrhizae, metabolism, anatomy and ultrastructure.

PubMed

Pereira, Lidiane Silva; de Araújo, Romária Pereira; de Oliveira, Priscila Souza; da Silva, Leandro Dias; Alves, Patricia Alves Casaes; Fernandes, Valéria Ferreira; Gross, Eduardo

2018-04-15

Solidago chilensis Meyen (Asteraceae) is a medicinal important plant with few studies on nutrition and metabolism and none information on cadmium phytotoxicity. The objective of this study was to investigate Cd induced responses on the growth and metabolism in S. chilensis and on arbuscular mycorrhiza (AM). The experiment was carried out in a greenhouse, consisting of a 5 × 4 factorial with five doses of manure (0, 3.5, 7, 14 and 21gdm -3 ) and four doses of cadmium (0, 25, 50 and 75mgdm -3 ) applied to a Dystrophic Ultisol. After 250 days of plant cultivation, biomass, nutrient content, photosynthetic rate, guaiacol peroxidase activity, mycorrhizal colonization, glomalin content, anatomical and ultrastucture were evaluated. Plants were significantly affected by interaction of manure and Cd doses with anatomical, ultrastructural, physiological and nutritional modifications. Manure applied into Cd contaminated soil significantly improved mycorrhizal colonization and glomalin production. The highest organic manure dose (21gdm -3 ) alleviated toxicity symptoms of Cd on S. chilensis. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of infectious virus dose and bloodmeal delivery method on susceptibility of Aedes aegypti and Aedes albopictus to chikungunya virus.

PubMed

Pesko, Kendra; Westbrook, Catherine J; Mores, Christopher N; Lounibos, L Philip; Reiskind, Michael H

2009-03-01

Chikungunya virus (CHIKV) is an arbovirus (genus Alphavirus, family Togaviridae) that has recently caused disease outbreaks in the Indian Ocean basin and southern Europe. These outbreaks could be associated with a possible shift in primary vector from Aedes aegypti to Ae. albopictus. To evaluate vector competence differences in possible CHIKV vectors, we evaluated the dose-dependant susceptibility of Florida strains of Ae. albopictus and Ae. aegypti for infection with a La Réunion island strain of CHIKV. Pledget and water-jacketed membrane feeding systems were also evaluated. We show that both Aedes spp. were susceptible to the highest CHIKV doses, whereas only Ae. albopictus developed disseminated infections after exposure to the two lowest doses. Infection rates for both mosquito species were significantly affected by the bloodmeal delivery method used. This information is important in assessing risk of an outbreak of imported CHIKV in the United States, in determining differences in vectorial capacity of these two vector species, and in evaluating arbovirus delivery methods in the laboratory.

Effects of Infectious Virus Dose and Bloodmeal Delivery Method on Susceptibility of Aedes aegypti and Aedes albopictus to Chikungunya Virus

PubMed Central

Pesko, Kendra; Westbrook, Catherine J.; Mores, Christopher N.; Lounibos, L. Philip; Reiskind, Michael H.

2009-01-01

Chikungunya virus (CHIKV) is an arbovirus (genus Alphavirus, family Togaviridae) that has recently caused disease outbreaks in the Indian Ocean basin and southern Europe. These outbreaks could be associated with a possible shift in primary vector from Aedes aegypti to Ae. albopictus. To evaluate vector competence differences in possible CHIKV vectors, we evaluated the dose-dependant susceptibility of Florida strains of Ae. albopictus and Ae. aegypti for infection with a La Réunion island strain of CHIKV. Pledget and water-jacketed membrane feeding systems were also evaluated. We show that both Aedes spp. were susceptible to the highest CHIKV doses, whereas only Ae. albopictus developed disseminated infections after exposure to the two lowest doses. Infection rates for both mosquito species were significantly affected by the bloodmeal delivery method used. This information is important in assessing risk of an outbreak of imported CHIKV in the United States, in determining differences in vectorial capacity of these two vector species, and in evaluating arbovirus delivery methods in the laboratory. PMID:19351094

Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV.

PubMed

Proetel, Ulrike; Pletsch, Nadine; Lauseker, Michael; Müller, Martin C; Hanfstein, Benjamin; Krause, Stefan W; Kalmanti, Lida; Schreiber, Annette; Heim, Dominik; Baerlocher, Gabriela M; Hofmann, Wolf-Karsten; Lange, Elisabeth; Einsele, Hermann; Wernli, Martin; Kremers, Stephan; Schlag, Rudolf; Müller, Lothar; Hänel, Mathias; Link, Hartmut; Hertenstein, Bernd; Pfirrman, Markus; Hochhaus, Andreas; Hasford, Joerg; Hehlmann, Rüdiger; Saußele, Susanne

2014-07-01

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874

SU-F-T-670: From the OR to the Radiobiology Lab: The Journey of a Small X-Ray Source

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

Lehmann, J; The University of Sydney, Sydney, NSW; The University of Newcastle, Newcastle, NSW

Purpose: Irradiation of small animal tumor models within laboratories is vital to radiobiological experiments. Often the animals are not able to be brought back into the lab after being taken out for irradiation. Cell biology laboratories benefit from irradiation capability available around the clock without regard to patient load in an associated radiotherapy clinic. Commercial systems are available, but bulky and expensive. Methods: An intraoperative kV irradiation system (IntraBeam™) designed to deliver spherical dose distributions to surgical cavities has been repurposed for the irradiation of cell plates and small laboratory animals. An applicator has been altered to allow for simple,more » open fields. Special collimators are being developed. BEAMnrc Monte Carlo simulations with the “NRC swept BEAM” source model have been performed to characterize the dose distributions, to develop optimal collimators and as basis for dose prescription. Measurements with radiochromic film and with an ionization chamber were performed to characterize the beam and to validate the simulations. Results: Using its highest setting (50 kV and 40 µA) the x-ray unit is capable of delivering dose rates over 1 Gy/min homogeneously to standard cell plates even without an optimized collimator. Smaller areas (tumors in animals) can be irradiated with significantly higher dose rates (> 20 Gy/min) depending on distance of the source to the tumor. The HVL was found to be 0.21 mm Al which means the shielding requirements for the device are easily achievable in the lab. Conclusion: A mobile irradiation facility is feasible. It will allow easier access to radiation for radiobiology experiments. The modified system is versatile in that for cell plates homogenous irradiations can be achieved through distance from the source, while for high dose rate small field irradiations the source can be brought in close proximity to the target.« less

An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection.

PubMed

Saber, Haleh; Del Valle, Pedro; Ricks, Tiffany K; Leighton, John K

2017-11-01

We retrospectively examined the nonclinical studies conducted with 17 CD3 bispecific constructs in support of first-in-human (FIH) trials in oncology. We also collected information on the design of dose-finding clinical trials. Sponsors have used different MABEL approaches for FIH dose selection. To better assess acceptable approaches, FIH doses were computed from nonclinical studies and compared to the maximum tolerated doses (MTDs) in patients, to the highest human doses (HHDs) when an MTD was not identified, or to the recommended human dose (RHD) for blinatumomab. We concluded that approaches based on receptor occupancy, highest non-severely toxic dose, or no-observed adverse effect level are not acceptable for selecting the FIH dose as they resulted in doses close to or above the MTDs, HHDs, or the RHD. A FIH dose corresponding to 10%-30% pharmacologic activity (PA) was an acceptable approach. A FIH dose corresponding to 50% PA was acceptable for all except one construct, potentially due to its biological or structural properties. The most common toxicities in animals and patients were those related to cytokine release. Doses were better tolerated when intra-animal or intra-patient dose escalation was used. Exposing naïve patients to an MTD achieved with intra-patient dose escalation design may be unsafe. Published by Elsevier Inc.

Delivery of risperidone from gels across porcine skin in vitro and in vivo in rabbits.

PubMed

Ning, Yuming; Chen, Xiaojin; Yu, Zhenwei; Liang, Wenquan; Li, Fanzhu

2018-05-01

The purpose of this study was to develop and evaluate a transdermal delivery system for RIS using hydrogels. First, the effects of different concentrations of hydroxypropyl methylcellulose and Carbomer 934 (CBR) on RIS permeation were investigated in porcine skin. The optimized formulation was chosen as the base gel to screen for penetration enhancers. The pharmacokinetics of the optimized RIS formulation was then studied in vitro in rabbits. A formulation with 0.5% CBR showed the highest RIS permeation and was selected as the base gel. RIS permeation was further increased by incorporation of Azone, lauryl alcohol, or menthol, and the enhancing effects of the three were dose-dependent. When each enhancer combined with propylene glycol (PG) a synergistic effect was found. A combination of 6% menthol and 6% PG exhibited highest RIS in vitro penetration rate and showed a high efficiency in vivo, with a relative bioavailability of 131.53% compared with intragastric administration. These findings showed that 1% RIS in 0.5% CBR, containing a combination of 6% menthol and 6% PG, can deliver doses of RIS that are therapeutically relevant for treating patients with schizophrenia.

Influence of exposure and geometric parameters on absorbed doses associated with common neuro-interventional procedures.

PubMed

Safari, Mohammad Javad; Wong, Jeannie Hsiu Ding; Jong, Wei Loong; Thorpe, Nathan; Cutajar, Dean; Rosenfeld, Anatoly; Ng, Kwan Hoong

2017-03-01

The purpose of this study was to investigate the effects of routine exposure parameters on patient's dose during neuro-interventional radiology procedures. We scrutinized the routine radiological exposure parameters during 58 clinical neuro-interventional procedures such as, exposure direction, magnification, frame rate, and distance between image receptor to patient's body and evaluate their effects on patient's dose using an anthropomorphic phantom. Radiation dose received by the occipital region, ears and eyes of the phantom were measured using MOSkin detectors. DSA imaging technique is a major contributor to patient's dose (80.9%) even though they are used sparingly (5.3% of total frame number). The occipital region of the brain received high dose largely from the frontal tube constantly placed under couch (73.7% of the total KAP). When rotating the frontal tube away from under the couch, the radiation dose to the occipital reduced by 40%. The use of magnification modes could increase radiation dose by 94%. Changing the image receptor to the phantom surface distance from 10 to 40cm doubled the radiation dose received by the patient's skin at the occipital region. Our findings provided important insights into the contribution of selected fluoroscopic exposure parameters and their impact on patient's dose during neuro-interventional radiology procedures. This study showed that the DSA imaging technique contributed to the highest patient's dose and judicial use of exposure parameters might assist interventional radiologists in effective skin and eye lens dose reduction for patients undergoing neuro-interventional procedures. Copyright © 2017 Associazione Italiana di Fisica Medica. All rights reserved.

Microstructural characterization and density change of 304 stainless steel reflector blocks after long-term irradiation in EBR-II

NASA Astrophysics Data System (ADS)

Huang, Y.; Wiezorek, J. M. K.; Garner, F. A.; Freyer, P. D.; Okita, T.; Sagisaka, M.; Isobe, Y.; Allen, T. R.

2015-10-01

While thin reactor structural components such as cladding and ducts do not experience significant gradients in dpa rate, gamma heating rate, temperature or stress, thick components can develop strong local variations in void swelling and irradiation creep in response to gradients in these variables. In this study we conducted microstructural investigations by transmission electron microscopy of two 52 mm thick 304-type stainless steel hex-blocks irradiated for 12 years in the EBR-II reactor with accumulated doses ranging from ∼0.4 to 33 dpa. Spatial variations in the populations of voids, precipitates, Frank loops and dislocation lines have been determined for 304 stainless steel sections exposed to different temperatures, different dpa levels and at different dpa rates, demonstrating the existence of spatial gradients in the resulting void swelling. The microstructural measurements compare very well with complementary density change measurements regarding void swelling gradients in the 304 stainless steel hex-block components. The TEM studies revealed that the original cold-worked-state microstructure of the unirradiated blocks was completely erased by irradiation, replaced by high densities of interstitial Frank loops, voids and carbide precipitates at both the lowest and highest doses. At large dose levels the amount of volumetric void swelling correlated directly with the gamma heating gradient-related temperature increase (e.g. for 28 dpa, ∼2% swelling at 418 °C and ∼2.9% swelling at 448 °C). Under approximately iso-thermal local conditions, volumetric void swelling was found to increase with dose level (e.g. ∼0.2% swelling at 0.4 dpa, ∼0.5% swelling at 4 dpa and ∼2% swelling at 28 dpa). Carbide precipitate formation levels were found to be relatively independent of both dpa level and temperature and induced a measurable densification. Void swelling was dominant at the higher dose levels and caused measurable decreases in density. Void swelling at the lowest doses was larger than might be expected based on the dpa level, an observation in agreement with earlier studies showing that the onset of void swelling is accelerated by decreasing dpa rates.

[Study of mumps immunity after administrating measles-mumps-rubella vaccine among children aged 2-7 years old in Jiangsu Province in 2015].

PubMed

Liu, Y B; Hu, Y; Deng, X Y; Wang, Z G; Sun, X; Lu, P S; Guo, H X; Tang, F Y; Zhou, M H

2017-07-06

Objective: To investigate the immunity to mumps after administrating measles-mumps-rubella vaccine (MMR) among children aged 2-7 years old in Jiangsu province in 2015. Methods: A total of 4 190 healthy children aged 2-7 years old, living in local places for at least 3 months, and having been vaccinated at least 1 dose MMR were recruited to the study from Wujin district of Changzhou city, Gaogang district of Taizhou city and Ganyu district of Lianyungang city by using stratified cluster random sampling method between September and November, 2015. Those who did not accept MMR vaccination, who refused venous blood collection, who had affected mumps according to the memory of parents or teachers and who were diagnosed serious disease by clinical doctors were excluded from study. The self-designed questionnaire was used to collect the general information of the subjects and their MMR immunization history; and 0.5-2.0 ml of venous blood was collected from each subject. ELISA was used to detect the mumps antibody level in the serum of patients. Positive was defined as the antibody level ≥108 mU/ml, and negative as <108 mU/ml. χ(2) test was used to compare the difference in positive rates among subjects; and analysis of variance was used to compare the GMC changes in different time points after MMR vaccination. Results: Among 4 190 children, 2 280 were males (54.42%) and 1 910 were females(45.58%), and the positive rate of IgG antibody was 81.38% (3 344). There were 3 156 (95.18%) children vaccinated with one dose MMR, 187 (4.80%) children with two dose MMR, and 1 (0.02%) child with three dose MMR. The difference in positive rate of IgG antibody among different aged subjects showed statistical significance (χ(2)=58.61, P< 0.001), the highest positive rate was in group of subjects aged 4-5 years old, at 89.43% (406/454), while the lowest positive rate was found among subjects aged 6-7 years old, at 75.63% (1 648/2 179). The positive rate after one dose of MMR vaccination was 79.14% (3 156/3 988), significantly less than it after two doses (93.03%, 187/201) (χ(2)=22.93, P< 0.001). The GMC level at years<1, 1-<2, 2-<3, 3-<4, ≥4 following one dose MMR in the 3 988 children was 152.47, 227.78, 167.08, 126.91, 79.43 mU/ml, whose difference was statistically significant ( F= 51.29, P< 0.001). Conclusion: The sero-prevalence of IgG antibody in the children aged 2-7 years old in Jiangsu province was high. The positive rate among who received two doses MMR was significantly higher than it among who received just one dose, and the GMC level waned with times.

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

PubMed

Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E

2017-03-01

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min -1 , n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

Dosimetry in differentiated thyroid carcinoma (12-1402R)

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

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

2013-01-15

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

Phase 1 first-in-human studies of the reactogenicity and immunogenicity of a recombinant meningococcal NspA vaccine in healthy adults.

PubMed

Halperin, Scott A; Langley, Joanne M; Smith, Bruce; Wunderli, Peter; Kaufman, Lisa; Kimura, Alan; Martin, Denis

2007-01-05

Neisserial surface protein A (NspA) is a highly conserved, surface-exposed outer membrane protein of Neisseria meningitidis that has been shown to induce a bactericidal immune response in animals against all pathogenic Neisserial serogroups. Healthy 18-50-year-old adults were assigned to receive, in a dose escalating manner, 3 doses of 1 of 5 formulations of an experimental, unfolded, recombinant NspA (rNspA) vaccine or placebo, or 1 dose of commercially available quadravalent (A, C, Y, W-135) meningococcal polysaccharide vaccine (Menomune((R))). Adverse events were collected during the first week post-immunization, prior to the next dose and 1 month after the last dose. Serum for measurement of hematological and biochemical parameters and antibodies by enzyme immunoassay and bactericidal assay were measured before the first dose, prior to the second dose and 1 month after the last dose of vaccine. The rNspA vaccine was well tolerated by recipients. Injection-site pain was reported more frequently by recipients of the three highest doses of rNspA compared to placebo but at similar rates to the licensed meningococcal polysaccharide vaccine. Adverse events were reported less frequently after subsequent doses in the three-dose series. An antibody rise measured by enzyme immunoassay was elicited with a dose-related increase that reached a maximum with the 125mug dose. Prolongation of the dosing interval between the second and third dose appeared to be associated with increased antibody levels. No bactericidal antibodies were detected after any of the rNspA formulations. The unfolded rNspA meningococcal vaccine was well tolerated and immunogenic in healthy adult volunteers but did not elicit bactericidal antibodies.

Four Transgenerational Demographic Performance of Moina macrocopa Exposed to Chronic Levels of Cadmium.

PubMed

Gama-Flores, José Luis; Huidobro-Salas, María Elena; Sarma, S S S; Nandini, S

2017-01-01

In this study, we quantified intergenerational, demographic variability of Moina macrocopa subjected to cadmium stress. Exposure of M macrocopa to cadmium (0.2, 0.3, and 0.4 mg/L as CdCl 2 ) through 4 consecutive generations revealed changes in demographic responses not only in survivorship variables but also in reproductive parameters. Long-term demographic responses varied differently, depending on the demographic trait and the concentration of heavy metal in the medium. With the exception of generation time, all life history traits were significantly and adversely influenced due to increase in Cd concentrations. The average life span of M macrocopa varied up to 40% depending on Cd level and the generation of exposure. The highest gross reproductive rates were recorded in controls, while the lowest (∼30% less) were recorded at the highest Cd level. Survival-weighted net reproductive rates were reduced by nearly 50% due to Cd toxicity. The rate of population increase per day of M macrocopa was also significantly affected (∼25%) by Cd as compared to controls. This cladoceran showed a dose-response to Cd toxicity with a significance in both magnitude and frequency of offspring production.

Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

PubMed

Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

2015-01-01

As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics. Copyright © 2014. Published by Elsevier Ltd.

Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration

PubMed Central

2014-01-01

Background Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies. Methods Sixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment. Results No adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose. Conclusions Fluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration. PMID:24602342

Particle exposure and inhaled dose during commuting in Singapore

NASA Astrophysics Data System (ADS)

Tan, Sok Huang; Roth, Matthias; Velasco, Erik

2017-12-01

Exposure concentration and inhaled dose of particles during door-to-door trips walking and using motorized transport modes (subway, bus, taxi) are evaluated along a selected route in a commercial district of Singapore. Concentrations of particles smaller than 2.5 μm in size (PM2.5), black carbon, particle-bound polycyclic aromatic hydrocarbons, number of particles, active surface area and carbon monoxide have been measured in-situ using portable instruments. Simultaneous measurements were conducted at a nearby park to capture the background concentrations. The heart rate of the participants was monitored during the measurements as a proxy of the inhalation rate used to calculate the inhaled dose of particles. All measured metrics were highest and well above background levels during walking. No significant difference was observed in the exposure concentration of PM2.5 for the three motorized transport modes, unlike for the metrics associated with ultrafine particles (UFP). The concentration of these freshly emitted particles was significantly lower on subway trips. The absence of combustion sources, use of air conditioning and screen doors at station platforms are effective measures to protect passengers' health. For other transport modes, sections of trips close to accelerating and idling vehicles, such as bus stops, traffic junctions and taxi stands, represent hotspots of particles. Reducing the waiting time at such locations will lower pollutants exposure and inhaled dose during a commute. After taking into account the effect of inhalation and travel duration when calculating dose, the health benefit of commuting by subway for this particular district of Singapore became even more evident. For example, pedestrians breathe in 2.6 and 3.2 times more PM2.5 and UFP, respectively than subway commuters. Public buses were the second best alternative. Walking emerged as the worst commuting mode in terms of particle exposure and inhaled dose.

Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius)

USGS Publications Warehouse

Hoffman, D.J.; Franson, J.C.; Pattee, O.H.; Bunck, C.M.; Murray, H.C.

1985-01-01

1. One-day old American kestrel (Faico sparverius) nestlings were orally dosed daily with 5 μl/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days.2. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell (δ-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups.3. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered.4. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development.5. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.

Hemodynamic responses to dexmedetomidine in critically injured intubated pediatric burned patients: a preliminary study.

PubMed

Shank, Erik S; Sheridan, Robert L; Ryan, Colleen M; Keaney, Timothy J; Martyn, J A Jeevendra

2013-01-01

Because of ineffectiveness and tolerance to benzodiazepines and opioids developing with time, drugs acting via other receptor systems (eg, α-2 agonists) have been advocated in burn patients to improve sedation and analgesia. This study in severely burned pediatric subjects examined the hemodynamic consequences of dexmedetomidine (Dex) administration. Eight intubated patients with ≥20 to 79% TBSA burns were studied between 7 and 35 days after injury. After baseline measurements of mean arterial blood pressure and heart rhythm were taken, each patient received a 1.0 µg/kg bolus of Dex followed by an ascending dose infusion protocol (0.7-2.5 µg/kg/hr), with each dose administered for 15 minutes. There was significant hypotension (27±7.5%, average drop in mean arterial pressure [MAP] ± SD), and a decrease in heart rate (HR; 19% ± 7, average drop in HR ± SD). The average HR decreased from 146 beats per minute to 120. No bradycardia (HR < 60) or heart blocks were observed. In three patients, the MAP decreased to <50mm Hg with the bolus dose of Dex. Of the remaining five patients, three patients completed the study receiving the highest infusion dose of Dex (2.5 µg/kg/hr), whereas in 2 patients the infusion part of the study was begun, but the study was stopped due to persistent hypotension (MAP < 50mm Hg). These observations indicate that a bolus dose of Dex (1.0 µg/kg for 10 minutes) and high infusion rates may require fluid resuscitation or vasopressor support to maintain normotension in critically injured pediatric burn patients.

Discriminative Stimulus Effects of Tramadol in Humans

PubMed Central

Duke, Angela N.; Bigelow, George E.; Lanier, Ryan K.

2011-01-01

Tramadol is an unscheduled atypical analgesic that acts as an agonist at μ-opioid receptors and inhibits monoamine reuptake. Tramadol can suppress opioid withdrawal, and chronic administration can produce opioid physical dependence; however, diversion and abuse of tramadol is low. The present study further characterized tramadol in a three-choice discrimination procedure. Nondependent volunteers with active stimulant and opioid use (n = 8) participated in this residential laboratory study. Subjects were trained to discriminate between placebo, hydromorphone (8 mg), and methylphenidate (60 mg), and tests of acquisition confirmed that all volunteers could discriminate between the training drugs. The following drug conditions were then tested during discrimination test sessions: placebo, hydromorphone (4 and 8 mg), methylphenidate (30 and 60 mg), and tramadol (50, 100, 200, and 400 mg). In addition to discrimination measures, which included discrete choice, point distribution, and operant responding, subjective and physiological effects were measured for each test condition. Both doses of hydromorphone and methylphenidate were identified as hydromorphone- and methylphenidate-like, respectively. Lower doses of tramadol were generally identified as placebo, with higher doses (200 and 400 mg) identified as hydromorphone, or opioid-like. The highest dose of tramadol increased ratings on the stimulant scale, but was not significantly identified as methylphenidate-like. Tramadol did not significantly increase subjective ratings associated with reinforcement. Taken together, these results extend previous work with tramadol as a potential medication for the treatment of opioid dependence and withdrawal, showing acute doses of tramadol exhibit a profile of effects similar to opioid agonists and may have abuse liability in certain populations. PMID:21467190

Systemic SMAD7 Gene Therapy Increases Striated Muscle Mass and Enhances Exercise Capacity in a Dose-Dependent Manner.

PubMed

Maricelli, Joseph W; Bishaw, Yemeserach M; Wang, Bo; Du, Min; Rodgers, Buel D

2018-03-01

Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity. A 2-month-long dose-escalation study was therefore conducted using 5 × 10 11 , 1 × 10 12 , and 5 × 10 12 vg/mouse and different tests of systemic muscle function. Body mass, skeletal muscle mass, heart mass, and forelimb grip strength were all increased in a dose-dependent manner, as was the fiber cross-sectional area of tibialis anterior muscles. Maximal oxygen consumption (VO 2 max), a measure of metabolic rate, was similarly enhanced during forced treadmill running, and although the total distance traveled was only elevated by the highest dose, all doses reduced the energy expenditure rate compared to control mice injected with an empty vector. Such improvements in VO 2 max are consistent with physiological cardiac hypertrophy, which is highly beneficial and a normal adaptive response to exercise. This was particularly evident at the lowest dose tested, which had minimal significant effects on skeletal muscle mass and/or function, but increased heart weight and exercise capacity. These results together suggest that AVGN7 enhances striated muscle mass and systemic muscle function. They also define minimally effective and optimal doses for future preclinical trials and toxicology studies and in turn will aid in establishing dose ranges for clinical trials.

Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

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

Mishra, Kavita K., E-mail: kmishra@radonc.ucsf.edu; Daftari, Inder K.; Weinberg, Vivian

2013-10-01

Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volumemore » histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose–volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose–volume parameters may be used to predict NVG risk.« less

Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat.

PubMed Central

Barrand, M. A.; Callingham, B. A.; Dobbin, P.; Hider, R. C.

1991-01-01

1. The fate and disposition of [59Fe]-ferric [3H]-maltol after intravenous administration were investigated in anaesthetized rats. Immediate dissociation of ferric iron from maltol took place in the circulation even with high doses of ferric maltol (containing 1 mg elemental iron). In plasma samples withdrawn within 1 min of injection and subjected to gel filtration, 59Fe eluted with the high molecular weight proteins whilst the tritium was associated with low molecular weight material. 2. The rates of elimination of 59Fe and of tritium from the plasma and their ultimate fate were very different. The half life for 59Fe in the plasma was around 70 min and 59Fe appeared mainly in the bone marrow and liver. There was an initial rapid exit of tritium from the plasma with a half life of around 12 min. This was followed either by a plateau or by a rise in tritium levels, involving entry of maltol metabolites into the circulation. These metabolites could be recovered in the urine. 3. Entry of 59Fe and of tritium into the blood plasma after intraduodenal administration of [59Fe]-ferric [3H]-maltol was also very different. At low doses of ferric maltol (containing 100 micrograms elemental iron), the tritium appeared in the plasma in highest amounts within seconds and then decreased whilst there was a slow rise in 59Fe levels. At higher doses of ferric maltol (containing 7 mg elemental iron), levels of 59Fe in the plasma were highest at 5 min and then fell whereas tritium levels rose steadily. Mucosal processing of 59Fe prevented further entry of iron at high dose into the circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1364845

Exposure-dependent incorporation of trifluridine into DNA of tumors and white blood cells in tumor-bearing mouse.

PubMed

Yamashita, Fumiaki; Komoto, Ikumi; Oka, Hiroaki; Kuwata, Keizo; Takeuchi, Mayuko; Nakagawa, Fumio; Yoshisue, Kunihiro; Chiba, Masato

2015-08-01

Trifluridine (TFT) is an antitumor component of a novel nucleoside antitumor agent, TAS-102, which consists of TFT and tipiracil hydrochloride (thymidine phosphorylase inhibitor). Incorporation of TFT into DNA is a probable mechanism of antitumor activity and hematological toxicity. The objective of this study was to examine the TFT incorporation into tumor- and white blood cell-DNA, and to elucidate the mechanism of TFT-related effect and toxicity. TFT effect on the colony formation of mouse bone marrow cells was also investigated. Pharmacokinetics of TFT was determined in nude mice after single oral administration of TAS-102, while the antitumor activity and body weight change were evaluated in the tumor-bearing nude mice after multiple oral administrations for 2 weeks. TFT concentrations in the blood- and tumor-DNA were determined by LC/MS/MS. The colony formation was evaluated by CFU-GM assay. TFT systemic exposure in plasma increased dose-dependently. The tumor growth rate and body weight gain decreased dose-dependently, but TFT concentrations in the DNA of tumor tissues and white blood cells increased dose-dependently. TFT inhibited colony formation of bone marrow cells in a concentration-dependent manner. A significant relationship between systemic exposure of TFT and pharmacological effects including the antitumor activity and body weight change was well explained by the TFT incorporation into DNA. TFT inhibited proliferations of mouse bone marrow cells and human colorectal carcinoma cells implanted to nude mice dose-dependently. The highest tolerable TFT exposure provides the highest antitumor activity, and the hematological toxicity may serve as a potential surrogate indicator of TAS-102 efficacy.

Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT.

PubMed

Doss, Mohan; Zhang, James J; Bélanger, Marie-José; Stubbs, James B; Hostetler, Eric D; Alpaugh, Katherine; Kolb, Hartmuth C; Yu, Jian Q

2010-12-01

F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans. Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software. The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data. Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

Tolerance to X-rays and Heavy Ions (Fe, He) in the Tardigrade Richtersius coronifer and the Bdelloid Rotifer Mniobia russeola

NASA Astrophysics Data System (ADS)

Jønsson, K. Ingemar; Wojcik, Andrzej

2017-02-01

The aim of this study was to analyze tolerance to heavy ions in desiccated animals of the eutardigrade Richtersius coronifer and the bdelloid rotifer Mniobia russeola within the STARLIFE project. Both species were exposed to iron (Fe) and helium (He) ions at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in Chiba, Japan, and to X-rays at the German Aerospace Center (DLR) in Cologne, Germany. Results show no effect of Fe and He on viability up to 7 days post-rehydration in both R. coronifer and M. russeola, while X-rays tended to reduce viability in R. coronifer at the highest doses. Mean egg production rate tended to decline with higher doses in R. coronifer for all radiation types, but the pattern was not statistically confirmed. In M. russeola, there was no such tendency for a dose response in egg production rate. These results confirm the previously reported high tolerance to high linear energy transfer (LET) radiation in tardigrades and show for the first time that bdelloid rotifers are also very tolerant to high-LET radiation. These animal phyla represent the most desiccation- and radiation-tolerant animals on Earth and provide excellent eukaryotic models for astrobiological research.

Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study.

PubMed

Arya, Sushila; Kupesic-Plavsic, Sanja; Mulla, Zuber D; Dwivedi, Alok K; Crisp, Zeni; Jose, Jisha; Noble, Luis S

2017-11-01

To assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients. Retrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3-D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four. Main outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%-41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients. Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation. Published by Elsevier B.V.

[The radiological situation before and after Chernobyl disaster].

PubMed

Leoniak, Marcin; Zonenberg, Anna; Zarzycki, Wiesław

2006-01-01

The nuclear reactor accident, which occurred on 26 April 1986 at Chernobyl, has been one of the greatest ecological disasters in human history. In our study we discussed the most recent data on the accident, and the natural and synthetic sources of radiation. According to the recent data, the air at Chernobyl had been contaminated with about 5300 PBq radionuclide activity (excluding rare gases), including 1760 PBq (131)I and 85 PBq (137)Cs. The highest radiation received by the liquidators (0.8-16 Gy), lower doses were received by the population which was evacuated or inhabited the contaminated areas (in which the level of (137)Cs activity deposited in the earth was 37 kBq/m(2)). In the European countries the highest mean radiation dose per year for the whole body in the first year after the accident was in Bulgaria (760 microSv), Austria (670 microSv) and Greece (590 microSv), while the lowest radiation dose was observed in Portugal (1.8 microSv) and Spain (4.2 microSv). In Poland the mean effective equivalent dose resulting from Chernobyl accident was 932 microSv and is close to the limited dose permitted in Poland, equalling 1 mSv/year. The highest radiation dose to thyroid was received by inhabitants of the states previously known as Bielskopodlaskie, Nowosadeckie and the north-east region of Poland. Lowest dose was received by inhabitants of the areas previously known as Slupski and Rzeszowski.

Variation among states in prescribing of opioid pain relievers and benzodiazepines--United States, 2012.

PubMed

Paulozzi, Leonard J; Mack, Karin A; Hockenberry, Jason M

2014-12-01

Overprescribing of opioid pain relievers (OPR) can result in multiple adverse health outcomes, including fatal overdoses. Interstate variation in rates of prescribing OPR and other prescription drugs prone to abuse, such as benzodiazepines, might indicate areas where prescribing patterns need further evaluation. CDC analyzed a commercial database (IMS Health) to assess the potential for improved prescribing of OPR and other drugs. CDC calculated state rates and measures of variation for OPR, long-acting/extended-release (LA/ER) OPR, high-dose OPR, and benzodiazepines. In 2012, prescribers wrote 82.5 OPR and 37.6 benzodiazepine prescriptions per 100 persons in the United States. State rates varied 2.7-fold for OPR and 3.7-fold for benzodiazepines. For both OPR and benzodiazepines, rates were higher in the South census region, and three Southern states were two or more standard deviations above the mean. Rates for LA/ER and high-dose OPR were highest in the Northeast. Rates varied 22-fold for one type of OPR, oxymorphone. Factors accounting for the regional variation are unknown. Such wide variations are unlikely to be attributable to underlying differences in the health status of the population. High rates indicate the need to identify prescribing practices that might not appropriately balance pain relief and patient safety. State policy makers might reduce the harms associated with the abuse of prescription drugs by implementing changes that will make the prescribing of these drugs more cautious and more consistent with clinical recommendations. Published by Elsevier Ltd.

Enhanced UV-B radiation during pupal stage reduce body mass and fat content, while increasing deformities, mortality and cell death in female adults of solitary bee Osmia bicornis.

PubMed

Wasielewski, Oskar; Wojciechowicz, Tatiana; Giejdasz, Karol; Krishnan, Natraj

2015-08-01

The effects of enhanced UV-B radiation on the oogenesis and morpho-anatomical characteristics of the European solitary red mason bee Osmia bicornis L. (Hymenoptera: Megachilidae) were tested under laboratory conditions. Cocooned females in the pupal stage were exposed directly to different doses (0, 9.24, 12.32, and 24.64 kJ/m(2) /d) of artificial UV-B. Our experiments revealed that enhanced UV-B radiation can reduce body mass and fat body content, cause deformities and increase mortality. Following UV exposure at all 3 different doses, the body mass of bees was all significantly reduced compared to the control, with the highest UV dose causing the largest reduction. Similarly, following UV-B radiation, in treated groups the fat body index decreased and the fat body index was the lowest in the group receiving the highest dose of UV radiation. Mortality and morphological deformities, between untreated and exposed females varied considerably and increased with the dose of UV-B radiation. Morphological deformities were mainly manifested in the wings and mouthparts, and occurred more frequently with an increased dose of UV. Cell death was quantified by the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (DNA fragmentation) during early stages of oogenesis of O. bicornis females. The bees, after UV-B exposure exhibited more germarium cells with fragmented DNA. The TUNEL test indicated that in germarium, low doses of UV-B poorly induced the cell death during early development. However, exposure to moderate UV-B dose increased programmed cell death. In females treated with the highest dose of UV-B the vast majority of germarium cells were TUNEL-positive. © 2014 Institute of Zoology, Chinese Academy of Sciences.

A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.

PubMed

Sellers, Edward M; Schoedel, Kerri; Bartlett, Cindy; Romach, Myroslava; Russo, Ethan B; Stott, Colin G; Wright, Stephen; White, Linda; Duncombe, Paul; Chen, Chien-Feng

2013-07-01

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain. A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers. The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed. Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day. In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies. © The Author(s) 2013.

Simulation of major space particles toward selected materials in a near-equatorial low earth orbit

NASA Astrophysics Data System (ADS)

Suparta, Wayan; Zulkeple, Siti Katrina

2017-05-01

A low earth orbit near the equator (LEO-NEqO) is exposed to the highest energies from galactic cosmic rays (GCR) and from trapped protons with a wide range of energies. Moreover, GCR fluxes were seen to be the highest in 2009 to 2010 when communication belonging to the RazakSAT-1 satellite was believed to have been lost. Hence, this study aimed to determine the influence of the space environment toward the operation of LEO-NEqO satellites by investigating the behavior of major space particles toward satellite materials. The space environment was referred to GCR protons and trapped protons. Their fluxes were obtained from the Space Environment Information System (SPENVIS) and their tracks were simulated through three materials using a simulation program called Geometry and Tracking (Geant4). The materials included aluminum (Al), gallium arsenide (GaAs) and silicon (Si). Then the total ionizing dose (TID) and non-ionizing dose (NIEL) were calculated for a three-year period. Simulations showed that GCR traveled at longer tracks and produced more secondary radiation than trapped protons. Al turned out to receive the lowest total dose, while GaAs showed to be susceptible toward GCR than Si. However, trapped protons contributed the most in spacecraft doses where Si received the highest doses. Finally, the comparison between two Geant4 programs revealed the estimated doses differed at <18%.

[Antibody persistence following on different vaccination strategies of domestic measles, mumps and rubella combined attenuated live vaccine: a 3-year follow-up study].

PubMed

He, H Q; Li, Q; Yan, R; Zhou, Y; Tang, X W; Deng, X; Xie, S Y; Chen, Z P

2017-04-06

Objective: To assess the 3-year antibody persistence after vaccination of domestic measles, mumps and rubella combined attenuated live vaccine (MMR) with different program. Methods: Children from three different vaccination strategies (Group 8 m MR: 8 months and 18 months vaccinated with measles-rubella combined attenuated live vaccine and domestic MMR,respectively; Group 8 m MMR: 8 months and 18 months both vaccinated with domestic MMR; Group 12 m MMR: 12 months and 22 months both vaccinated with domestic MMR ) were followed up in Zhejiang province in July 2015. There were 170 participants in Group 8 m MR, 171 participants in Group 8 m MMR and 173 participants in Group 12 m MMR selected by simple random sampling method .Blood samples (venous blood 2-3 ml) were collected 1 month after the first dose vaccination of MMR (only in Group 8 m MMR and Group 12 m MMR) and 3 years (36-38 months) after the last dose vaccination of MMR and tested for antibody IgG against Measles, Mumps and Rubella using ELISA. Seropostive rate and Geometric mean concentration (GMC) were calculated and compared among different groups by Chi-square test or Fisher exact test and Kruskal-Wallis H test. Results: A total of 514 participants (8 m MR: 170; 8 m MMR:171; 12 m MMR:173) were enrolled. The overall seropositivity rate of measles, mumps and rubella was 98.1% (504), 93.4% (480) and 88.1% (453), respectively, with corresponding GMC was 1 012.33 mU/ml, 502.87 U/ml and 50.53 U/ml respectively. There was no significant difference of seropositivity rate for measles among three groups (all groups were>97%). The highest seropositivity rate for mumps was found in the Group 12 m MMR with the rate of 98.8% (171/173), followed by Group 8 m MMR and Group 8 m MR with 93.0% (159/171) and 88.2%(150/170) respectively (Fisher exact test, P< 0.001). The highest seropositivity rate for rubella was also found in the Group 12 m MMR with the rate of 94.8% (164/173), followed by Group 8 m MMR and Group 8 m MR with 86.6%(148/171) and 82.9%(141/170) respectively (Fisher exact test, P= 0.002). The highest GMC of antibody against measles, mumps and rubella were all found in Group 12 m MMR, with 1 217.30 (1 119.35-1 323.82) mU/ml, 717.07 (643.83-798.65) U/ml and 62.54(56.21-69.58) U/ml respectively. The lowest GMC of antibody against measles and mumps were both in Group 12 m MR with 812.01 (734.52-897.67) mU/ml and 363.28 (305.42-432.11) U/ml respectively. The lowest GMC of antibody against rubella was in Group 8 m MMR with 44.10 (39.08-49.76) U/ml. These differences of GMCs among three groups were all reach significant means ( P< 0.05). Conclusion: High level seropostive rates and GMCs were exist against measles and rubella after 3-year vaccination of domestic MMR among different program. Higher antibody level against mumps were found in those children with two doses vaccination of MMR.

epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat

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

Rebouche, C.J.; Lehman, L.J.; Olson, L.

1986-05-01

Rates of carnitine biosynthesis in mammals depend on the availability of substrates and the activity of enzymes subserving the pathway. This study was undertaken to test the hypothesis that the availability of epsilon-N-trimethyllysine is rate-limiting for synthesis of carnitine in the growing rat and to evaluate diet as a source of this precursor for carnitine biosynthesis. Rats apparently absorbed greater than 90% of a tracer dose of (methyl-/sup 3/H)epsilon-N-trimethyllysine, and approximately 30% of that was incorporated into tissues as (/sup 3/H)carnitine. Rats given oral supplements of epsilon-N-trimethyllysine (0.5-20 mg/d), but no dietary carnitine, excreted more carnitine than control animals receivingmore » no dietary epsilon-N-trimethyllysine or carnitine. Rates of carnitine excretion increased in a dose-dependent manner. Tissue and serum levels of carnitine also increased with dietary epsilon-N-trimethyllysine supplementation. There was no evidence that the capacity for carnitine biosynthesis was saturated even at the highest level of oral epsilon-N-trimethyllysine supplementation. Common dietary proteins (casein, soy protein and wheat gluten) were found to be poor sources of epsilon-N-trimethyllysine for carnitine biosynthesis. The results of this study indicate that the availability of epsilon-N-trimethyllysine limits the rate of carnitine biosynthesis in the growing rat.« less

The assessment of ionising radiation impact on the cooling pond freshwater ecosystem non-human biota from the Ignalina NPP operation beginning to shut down and initial decommissioning.

PubMed

Mazeika, J; Marciulioniene, D; Nedveckaite, T; Jefanova, O

2016-01-01

The radiological doses to non-human biota of freshwater ecosystem in the Ignalina NPP cooling pond - Lake Druksiai were evaluated for several cases including the plant's operation period and initial decommissioning activities, using the ERICA 1.2 code with IAEA SRS-19 models integrated approach and tool. Among the Lake Druksiai freshwater ecosystem reference organisms investigated the highest exposure dose rate was determined for bottom fauna - benthic organisms (mollusc-bivalves, crustaceans, mollusc-gastropods, insect larvae), and among the other reference organisms - for vascular plants. The mean and maximum total dose rate values due to anthropogenic radionuclide ionising radiation impact in all investigated cases were lower than the ERICA screening dose rate value of 10 μGy/h. The main exposure of reference organisms as a result of Ignalina NPP former effluent to Lake Druksiai is due to ionizing radiation of radionuclides (60)Co and (137)Cs, of predicted releases to Lake Druksiai during initial decommissioning period - due to radionuclides (60)Co, (134)Cs and (137)Cs, and as a result of predicted releases to Lake Druksiai from low- and intermediate-level short-lived radioactive waste disposal site in 30-100 year period - due to radionuclides (99)Tc and (3)H. The risk quotient expected values in all investigated cases were <1, and therefore the risk to non-human biota can be considered negligible with the exception of a conservative risk quotient for insect larvae. Radiological protection of non-human biota in Lake Druksiai, the Ignalina NPP cooling pond, is both feasible and acceptable. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of dose from kV cone-beam computed tomography during radiotherapy: a comparison of methodologies

NASA Astrophysics Data System (ADS)

Buckley, J.; Wilkinson, D.; Malaroda, A.; Metcalfe, P.

2017-01-01

Three alternative methodologies to the Computed-Tomography Dose Index for the evaluation of Cone-Beam Computed Tomography dose are compared, the Cone-Beam Dose Index, IAEA Human Health Report No. 5 recommended methodology and the AAPM Task Group 111 recommended methodology. The protocols were evaluated for Pelvis and Thorax scan modes on Varian® On-Board Imager and Truebeam kV XI imaging systems. The weighted planar average dose was highest for the AAPM methodology across all scans, with the CBDI being the second highest overall. A 17.96% and 1.14% decrease from the TG-111 protocol to the IAEA and CBDI protocols for the Pelvis mode and 18.15% and 13.10% decrease for the Thorax mode were observed for the XI system. For the OBI system, the variation was 16.46% and 7.14% for Pelvis mode and 15.93% to the CBDI protocol in Thorax mode respectively.

Proteomic and Epigenetic Analysis of Rice after Seed Spaceflight and Ground-Base Ion Radiations

NASA Astrophysics Data System (ADS)

Wang, Wei; Sun, Yeqing; Peng, Yuming; Zhao, Qian; Wen, Bin; Yang, Jun

Highly ionizing radiation (HZE) in space is considered as main factor causing biological effects to plant seeds. In previous work, we compared the proteomic profiles of rice plants growing after seed spaceflights to ground controls by two-dimensional difference gel electrophoresis (2-D DIGE) with mass spectrometry and found that the protein expression profiles were changed and differentially expressed proteins participated in most of the biological processes of rice. To further evaluate the dosage effects of space radiation and compare between low- and high-dose ion effects, we carried out three independent ground-base ionizing radiation experiments with different cumulative doses (low-dose range: 2~1000mGy, high-dose range: 2000~20000mGy) to rice seeds and performed proteomic analysis of seedlings. We found that protein expression profiles showed obvious boundaries between low- and high-dose radiation groups. Rates of differentially expressed proteins presented a dose-dependent effect, it reached the highest value at 2000mGy dosage point in all three radiation experiments coincidently; while proteins responded to low-dose radiations preferred to change their expressions at the minimum dosage (2mGy). Proteins participating in rice biological processes also responded differently between low- and high-dose radiations: proteins involved in energy metabolism and photosynthesis tended to be regulated after low-dose radiations while stress responding, protein folding and cell redox homeostasis related proteins preferred to change their expressions after high-dose radiations. By comparing the proteomic profiles between ground-base radiations and spaceflights, it was worth noting that ground-base low-dose ion radiation effects shared similar biological effects as space environment. In addition, we discovered that protein nucleoside diphosphate kinase 1 (NDPK1) showed obvious increased regulation after spaceflights and ion radiations. NDPK1 catalyzes nucleotide metabolism and is reported to be involved in DNA repair process. Its expression sensitivity and specificity were confirmed by RT-PCR and western blot analysis, indicating its potential to be used as space radiation biomarker. Space radiations might induce epigenetic effects on rice plants, especially changes of DNA methylation. Early results suggested that there were correlations between DNA methylation polymorphic and genomic mutation rates. In addition, the 5-methylcytosine located in coding gene’s promoter and exon regions could regulate gene expressions thus influence protein expressions. So whether there is correlation between genome DNA methylation changes and protein expression profile alterations caused by space radiation is worth for further investigation. Therefore we used the same rice samples treated by carbon ion radiation with different doses (0, 10, 20,100, 200, 1000, 2000, 5000, 20000mGy) and applied methylation sensitive amplification polymorphism (MSAP) for scanning genome DNA methylation changes. Interestingly, DNA methylation polymorphism rates also presented a dose-dependent effect and showed the same changing trend as rates of differentially expressed proteins. Whether there are correlations between epigenetic and proteomic effects of space radiation is worth for further investigation.

Effects of intracerebroventricular administered fluoxetine on cardio-ventilatory functions in rainbow trout (Oncorhynchus mykiss).

PubMed

Kermorgant, Marc; Lancien, Frédéric; Mimassi, Nagi; Tyler, Charles R; Le Mével, Jean-Claude

2014-09-01

Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor present in the aquatic environment which is known to bioconcentrate in the brains of exposed fish. FLX acts as a disruptor of various neuroendocrine functions in the brain, but nothing is known about the possible consequence of FLX exposure on the cardio-ventilatory system in fish. Here we undertook to investigate the central actions of FLX on ventilatory and cardiovascular function in unanesthetized rainbow trout (Oncorhynchus mykiss). Intracerebroventricular (ICV) injection of FLX (dosed between 5 and 25 μg) resulted in a significantly elevated total ventilation (VTOT), with a maximum hyperventilation of +176% (at a dose of 25μg) compared with vehicle injected controls. This increase was due to an increase in ventilatory amplitude (VAMP: +126%) with minor effects on ventilatory frequency. The highest dose of FLX (25 μg) produced a significant increase in mean dorsal aortic blood pressure (PDA: +20%) without effects on heart rate (ƒH). In comparison, intra-arterial injections of FLX (500-2,500 μg) had no effect on ventilation but the highest doses increased both PDA and ƒH. The ICV and IA cardio-ventilatory effects of FLX were very similar to those previously observed following injections of 5-HT, indicating that FLX probably acts via stimulating endogenous 5-HT activity through inhibition of 5-HT transporter(s). Our results demonstrate for the first time in fish that FLX administered within the brain exerts potent stimulatory effects on ventilation and blood pressure increase. The doses of FLX given to fish in our study are higher than the brain concentrations of FLX in fish that result from acute exposure to FLX through the water. Nonetheless, our results indicate possible disrupting action of long term exposure to FLX discharged into the environment on central target sites sensitive to 5-HT involved in cardio-ventilatory control. Copyright © 2013 Elsevier Inc. All rights reserved.

Awareness and Knowledge Among Internal Medicine Resident Trainees for Dose Adjustment of Analgesics and Neuropsychotropic Medications in CKD.

PubMed

Saad, Chadi Y; Fogel, Joshua; Rubinstein, Sofia

2018-03-01

Errors in drug dosing lead to poor patient outcomes and are common in patients with chronic kidney disease (CKD). Because the majority of patients with CKD are being treated by physicians specializing in internal medicine, we studied the awareness and knowledge that internal medicine resident trainees (IMRTs) have regarding the correct dosage of commonly used analgesic and neuropsychotropic medications for patients with CKD. We surveyed 353 IMRTs about their awareness of whether a medication needs dose adjustment in patients with CKD and knowledge for medication adjustment by level of glomerular filtration rate. There were high percentages for lack of awareness and knowledge. For analgesics, this lack of awareness/knowledge was highest for acetaminophen (awareness 83.0%, knowledge 90.9%). For neuropsychotropics, this was highest for paroxetine (awareness 74.5%, knowledge 91.5%). Analyses for postgraduate year (PGY) -1 trainees and PGY-2 trainees for analgesics showed higher odds for lack of awareness for tramadol (PGY-1 odds ratio [OR] 2.37, 95% confidence interval [CI] 1.2-4.62, P < 0.05; PGY-2 OR 2.34, 95% CI 1.16-4.72, P < 0.05) and for lack of knowledge for meperedine (PGY-1 OR 4.01, 95% CI 1.81-8.89, P < 0.05; PGY-2 OR 3.30, 95% CI 1.44-7.59, P < 0.05). Nephrology residency rotation for the neuropsychotropic medication of gabapentin showed lower odds for both lack of awareness (OR 0.56, 95% CI 0.32-0.97, P < 0.05) and knowledge (OR 0.52, 95% CI 0.27-0.997, P < 0.05). Awareness and knowledge are poor among IMRTs for dose adjustments of analgesics and neuropsychotropic medication classes in patients with CKD. There should be a renewed focus during IMRTs' residency on additional nephrology exposure and formal didactic educational training to help them better manage complex treatment regimens to prevent medication dosing errors.

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

USGS Publications Warehouse

Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

2014-01-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

2008-01-01

The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

Biota Modeling in EPA's Preliminary Remediation Goal and Dose Compliance Concentration Calculators for Use in EPA Superfund Risk Assessment: Explanation of Intake Rate Derivation, Transfer Factor Compilation, and Mass Loading Factor Sources

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

Manning, Karessa L.; Dolislager, Fredrick G.; Bellamy, Michael B.

The Preliminary Remediation Goal (PRG) and Dose Compliance Concentration (DCC) calculators are screening level tools that set forth Environmental Protection Agency's (EPA) recommended approaches, based upon currently available information with respect to risk assessment, for response actions at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) sites, commonly known as Superfund. The screening levels derived by the PRG and DCC calculators are used to identify isotopes contributing the highest risk and dose as well as establish preliminary remediation goals. Each calculator has a residential gardening scenario and subsistence farmer exposure scenarios that require modeling of the transfer of contaminants frommore » soil and water into various types of biota (crops and animal products). New publications of human intake rates of biota; farm animal intakes of water, soil, and fodder; and soil to plant interactions require updates be implemented into the PRG and DCC exposure scenarios. Recent improvements have been made in the biota modeling for these calculators, including newly derived biota intake rates, more comprehensive soil mass loading factors (MLFs), and more comprehensive soil to tissue transfer factors (TFs) for animals and soil to plant transfer factors (BV's). New biota have been added in both the produce and animal products categories that greatly improve the accuracy and utility of the PRG and DCC calculators and encompass greater geographic diversity on a national and international scale.« less

Anoxia-conditioning hormesis alters the relationship between irradiation doses for survival and sterility in the cactus moth, Cactoblastis cactorum (Lepidoptera: Pyralidae)

USDA-ARS?s Scientific Manuscript database

One of the most important components of a Sterile Insect Technique (SIT) program is appropriate irradiation dose. Knowing the organismal dose-response enables the selection of a dose that induces the highest level of sterility while preserving the sexual competitiveness and quality of the sterile in...

Penalization of aperture complexity in inversely planned volumetric modulated arc therapy

PubMed Central

Younge, Kelly C.; Matuszak, Martha M.; Moran, Jean M.; McShan, Daniel L.; Fraass, Benedick A.; Roberts, Donald A.

2012-01-01

Purpose: Apertures obtained during volumetric modulated arc therapy (VMAT) planning can be small and irregular, resulting in dosimetric inaccuracies during delivery. Our purpose is to develop and integrate an aperture-regularization objective function into the optimization process for VMAT, and to quantify the impact of using this objective function on dose delivery accuracy and optimized dose distributions. Methods: An aperture-based metric (“edge penalty”) was developed that penalizes complex aperture shapes based on the ratio of MLC side edge length and aperture area. To assess the utility of the metric, VMAT plans were created for example paraspinal, brain, and liver SBRT cases with and without incorporating the edge penalty in the cost function. To investigate the dose calculation accuracy, Gafchromic EBT2 film was used to measure the 15 highest weighted apertures individually and as a composite from each of two paraspinal plans: one with and one without the edge penalty applied. Films were analyzed using a triple-channel nonuniformity correction and measurements were compared directly to calculations. Results: Apertures generated with the edge penalty were larger, more regularly shaped and required up to 30% fewer monitor units than those created without the edge penalty. Dose volume histogram analysis showed that the changes in doses to targets, organs at risk, and normal tissues were negligible. Edge penalty apertures that were measured with film for the paraspinal plan showed a notable decrease in the number of pixels disagreeing with calculation by more than 10%. For a 5% dose passing criterion, the number of pixels passing in the composite dose distributions for the non-edge penalty and edge penalty plans were 52% and 96%, respectively. Employing gamma with 3% dose/1 mm distance criteria resulted in a 79.5% (without penalty)/95.4% (with penalty) pass rate for the two plans. Gradient compensation of 3%/1 mm resulted in 83.3%/96.2% pass rates. Conclusions: The use of the edge penalty during optimization has the potential to markedly improve dose delivery accuracy for VMAT plans while still maintaining high quality optimized dose distributions. The penalty regularizes aperture shape and improves delivery efficiency. PMID:23127107

Current status of Enterobius vermicularis infection in primary schoolchildren in Miaoli County and Taichung County, Taiwan.

PubMed

Wang, Cheng-Chieh; Lee, Yuan-Fang; Chang, Chih-Cheng; Lee, Nie-Sue; Chen, Po-Yen; Huang, Fang-Liang; Liou, Nuo-Wei

2009-10-01

No epidemiological survey of the prevalence of Enterobius vermicularis infection in Miaoli County and Taichung County has been conducted. This epidemiological survey was performed to describe the profile of E. vermicularis infection in schoolchildren in Miaoli County and Taichung County. The first part of this study was conducted between November 2005 and February 2006 in Miaoli County. 44,071 primary schoolchildren from 18 districts were examined by 2 consecutive-day adhesive cellophane perianal swabs to estimate the infection rate. The second part was performed between October 2006 and January 2007 in Taichung County. 24,382 primary schoolchildren from 14 districts were examined. In Miaoli County, the infection rate was 2.39% (1054/44,071). The infection rate was highest in the Taian (6.69%; 20/299), Shytarn (4.49%; 11/245), and Dahu townships (3.6%; 40/1111). In Taichung County, the infection rate was 2.95% (720/24,382). The infection rate was highest in the Da-an (5.46%; 26/476) and Heping townships (4.48%; 9/201). The infection rate for a family with > or =3 children was significantly higher than that for a family with < or =2 children (p = 0.007). The frequency of washing linen and cleaning bedclothes significantly affected the infection rate of enterobiasis (p < 0.01). The efficacy rate for mebendazole was 96%, with no difference between 1 and 2 doses. The number of children per family and the frequency of washing linen and cleaning bedclothes were the most important factors for transmission of pinworm infection among the groups surveyed.

Free radical scavenging, antidiarrheal and anthelmintic activity of Pistia stratiotes L. extracts and its phytochemical analysis.

PubMed

Bin Karim, Mohammed Faisal; Imam, Hasan; Sarker, Md Moklesur-Rahman; Uddin, Nizam; Hasan, Nahid; Paul, Nirmala; Haque, Tahmina

2015-05-01

In this phyto-pharmacological screening of Pistia stratiotes L leaf and root extracts each separately in two different solvents demonstrated its potential medicinal value. Apparent antioxidant value is demonstrated by DPPH, Nitric oxide scavenging and Ferric ion reducing method. Additionally, total flavonoid and phenolic compounds were measured. The leaf methanolic extract scavenged both nitric oxide (NO) and DPPH radical with a dose dependent manner. But the pet ether fraction of root was found to have highest efficacy in Fe(3±) reducing power assay. Flavonoid was found to contain highest in the pet ether fraction of root (411.35mg/g) in terms of quercetin equivalent, similarly highest amount (34.96mg/g) of total phenolic compounds (assayed as gallic acid equivalents) were found to contain in the same fraction. The methanolic fractions appeared less cytotoxic compared to pet ether extracts. The plant extracts caused a dose dependent decrease in faecal droppings in both castor oil and magnesium sulphate induced diarrhea, where as leaf extracts in each solvent appeared most effective. Also, the plant extracts showed anthelmintic activity in earthworm by inducing paralysis and death in a dose dependent manner. At highest doses (50 mg/ml) all fractions were almost effective as the positive control piperazine citrate (10 mg/ml). Thus, besides this cytotoxic effect it's traditional claim for therapeutic use can never be overlooked.

Variation of radiation level and radionuclide enrichment in high background area.

PubMed

Shetty, P K; Narayana, Y

2010-12-01

Significantly high radiation level and radionuclide concentration along Quilon beach area of coastal Kerala have been reported by several investigators. Detailed gamma radiation level survey was carried out using a portable scintillometer. Detailed studies on radionuclides concentration in different environmental matrices of high background areas were undertaken in the coastal areas of Karunagapalli, Kayankulam, Chavara, Neendakara and Kollam to study the distribution and enrichment of the radionuclides in the region. The absorbed gamma dose rates in air in high background area are in the range 43-17,400nGyh⁻¹. Gamma radiation level is found to be maximum at a distance of 20m from the sea waterline in all beaches. The soil samples collected from different locations were analysed for primordial radionuclides by gamma spectrometry. The activity of primordial radionuclides was determined for the different size fractions of soil to study the enrichment pattern. The highest activity of (232)Th and (226)Ra was found to be enriched in 125-63μ size fraction. The preferential accumulation of (40)K was found in <63μ fraction. The minimum (232)Th activity was 30.2Bqkg⁻¹, found in 1000-500μ particle size fraction at Kollam and maximum activity of 3250.4Bqkg⁻¹ was observed in grains of size 125-63μ at Neendakara. The lowest (226)Ra activity observed was 33.9Bqkg⁻¹ at Neendakara in grains of size 1000-500μ and the highest activity observed was 482.6Bqkg⁻¹ in grains of size 125-63μ in Neendakara. The highest (40)K activity found was 1923Bqkg⁻¹ in grains of size <63μ for a sample collected from Neendakara. A good correlation was observed between computed dose and measured dose in air. The correlation between (232)Th and (226)Ra was also moderately high. The results of these investigations are presented and discussed in this paper. Copyright © 2010 Elsevier Ltd. All rights reserved.

Vaccine exemptions and the kindergarten vaccination coverage gap.

PubMed

Smith, Philip J; Shaw, Jana; Seither, Ranee; Lopez, Adriana; Hill, Holly A; Underwood, Mike; Knighton, Cynthia; Zhao, Zhen; Ravanam, Megha Shah; Greby, Stacie; Orenstein, Walter A

2017-09-25

Vaccination requirements for kindergarten entry vary by state, but all states require 2 doses of measles containing vaccine (MCV) at kindergarten entry. To assess (i) national MCV vaccination coverage for children who had attended kindergarten; (ii) the extent to which undervaccination after kindergarten entry is attributable to parents' requests for an exemption; (iii) the extent to which undervaccinated children had missed opportunities to be administered missing vaccine doses among children whose parent did not request an exemption; and (iv) the vaccination coverage gap between the "highest achievable" MCV coverage and actual MCV coverage among children who had attended kindergarten. A national survey of 1465 parents of 5-7year-old children was conducted during October 2013 through March 2014. Vaccination coverage estimates are based provider-reported vaccination histories. Children have a "missed opportunity" for MCV if they were not up-to-date and if there were dates on which other vaccines were administered but not MCV. The "highest achievable" MCV vaccination coverage rate is 100% minus the sum of the percentages of (i) undervaccinated children with parents who requested an exemption; and (ii) undervaccinated children with parents who did not request an exemption and whose vaccination statuses were assessed during a kindergarten grace period or period when they were provisionally enrolled in kindergarten. Among all children undervaccinated for MCV, 2.7% were attributable to having a parent who requested an exemption. Among children who were undervaccinated for MCV and whose parent did not request an exemption, 41.6% had a missed opportunity for MCV. The highest achievable MCV coverage was 98.6%, actual MCV coverage was 90.9%, and the kindergarten vaccination gap was 7.7%. Vaccination coverage may be increased by schools fully implementing state kindergarten vaccination laws, and by providers assessing children's vaccination status at every clinic visit, and administering missed vaccine doses. Published by Elsevier Ltd.

Evaluation of Salmonella enterica serovar Typhi (Ty2 aroC-ssaV-) M01ZH09, with a defined mutation in the Salmonella pathogenicity island 2, as a live, oral typhoid vaccine in human volunteers.

PubMed

Kirkpatrick, B D; McKenzie, Robin; O'Neill, J Patrick; Larsson, Catherine J; Bourgeois, A Louis; Shimko, Janet; Bentley, Matthew; Makin, Jill; Chatfield, Steve; Hindle, Zoë; Fidler, Christine; Robinson, Brad E; Ventrone, Cassandra H; Bansal, Nivedita; Carpenter, Colleen M; Kutzko, Deborah; Hamlet, Sandra; LaPointe, Casey; Taylor, David N

2006-01-12

Salmonella enterica serovar Typhi strains with mutations in the Salmonella pathogenicity island-2 (SPI-2) may represent an effective strategy for human vaccine development, and a vectoring system for heterologous antigens. S. Typhi (Ty2 aroC-ssaV-) M01ZH09 is an attenuated, live, oral typhoid vaccine harboring defined deletion mutations in ssaV, which encodes an integral component in the SPI-2 type III secretion system (TTSS), as well as a mutation in an aromatic biosynthetic pathway needed for bacterial growth in vivo (aroC). SPI-2 mutant vaccines have yet to be evaluated in a large, randomized human trial. A simplified or single-oral dose oral typhoid vaccine using the SPI-2 strategy would offer significant advantages over the currently licensed typhoid vaccines. We performed a double-blinded, placebo-controlled, dose-escalating clinical trial in 60 healthy adult volunteers to determine the tolerability and immunogenicity of a single dose of M01ZH09. Three groups of 20 healthy adult volunteers were enrolled; 16 in each group received a single oral dose of the freeze-dried vaccine at 5 x 10(7), 5 x 10(8) or 5 x 10(9)CFU in a bicarbonate buffer. Four volunteers in each cohort received placebo in the same buffer. Adverse events were infrequent and not statistically different between vaccine and placebo recipients, although two subjects in the mid-range dose and three subjects in the highest dose had temperature measurements >37.5 degrees C. No blood or urine cultures were positive for M01ZH09, and fecal shedding was brief. The immune response was dose-related; the highest vaccine dose (5 x 10(9)CFU) was the most immunogenic. All tested subjects receiving the highest dose had a significant ASC response (mean 118 spots/10(6) cells). A >or=4-fold increase in antibody titer for S. Typhi LPS or flagellin was detected in 75% of volunteers in the highest-dose cohort by day 28. The SPI-2 mutant vaccine, M01ZH09, is a promising typhoid vaccine candidate and deserves further study as a vectoring system for heterologous vaccine antigens.

[Vaccination against hepatitis B. Impact of vaccination programmes after 20 years of use in Spain. Is it time for a change?].

PubMed

Arístegui Fernández, Javier; Díez-Domingo, Javier; Marés Bermúdez, Josep; Martinón Torres, Federico

2015-02-01

The highest incidence rate of hepatitis B (HB) in Spain is detected in adults between 20 and 54 years old, whereas the incidence in children under 1 year old is almost nil. The low prevalence of HB in children under 1 year is mainly due to the success of gestational screening strategies for the detection of HBsAg(+) in pregnant women, and vaccination campaigns during childhood. Currently, in Spain, the last dose of the HB included in the national childhood immunization program is administered at 6 months of age, although some studies show that delaying the age of the administration of the last dose of HB vaccine and increasing the time between doses, may improve immune memory by offering greater protection against this virus in the adulthood. In this article, the impact of HB vaccination in Spain is reviewed, and other potential vaccination strategies in our environment are discussed, such as extending the interval between doses, and administering the last dose in the second year of life, adapting the valid strategy in Spain to the current epidemiological context in order to reduce the prevalence of HB in adulthood. Copyright © 2015. Published by Elsevier España.

Enhanced enzymatic hydrolysis of kenaf core using irradiation and dilute acid

NASA Astrophysics Data System (ADS)

Lee, Byoung-Min; Jeun, Joon-Pyo; Kang, Phil-Hyun

2017-01-01

This study was performed to determine the effect of electron beam dose and enzymatic hydrolysis time for production of sugar such as glucose and xylose. After kenaf core was exposed to an irradiation dose that ranged from 0 to 500 kGy, the irradiated kenaf core was treated with a 3% (v/v) sulfuric acid solution using an autoclave for 5 h at 120 °C. The pretreated kenaf core was subsequently subjected to enzymatic hydrolysis at 50 °C in a shaking water bath at 150 rpm for 12, 24, 48, and 72 h. The determined enzyme activity rates were 70 FPU (Celluclast 1.5 L) and 40 CBU (Novozyme-188). The crystallinity index decreased from 50.6% in a non-pretreated kenaf core to 27.7% in kenaf core that was subjected to the two-stage pretreatment at dose of 500 kGy. The sugar yield of the two-stage pretreated kenaf core increased with an increase in irradiation dose. The sugar yield after 72 h of enzymatic hydrolysis was 73.6% at its highest with an irradiation dose of 500 kGy. The enhancement of enzymatic hydrolysis by two-stage pretreatment was more effective than non- and single pretreatment (36.9%, 40.6% and 44.0% in non-pretreatment, electron beam and dilute acid, respectively).

Renal hemodynamic response to galanin: importance of elevated plasma glucose.

PubMed

Premen, A J

1989-12-01

Although recent data point to a possible indirect role for galanin in modulating renal blood flow (RBF) and fluid homeostasis in experimental animals, there have been no systematic studies exploring the possible direct effects of the peptide on the mammalian kidney. We ascertained the RBF, glomerular filtration rate (GFR) and plasma glucose responses to direct intrarenal infusion of three progressively increasing doses of synthetic galanin in anesthetized dogs. A 50 ng/kg per min dose (n = 6) failed to affect RBF, GFR or arterial plasma glucose (APG). Yet, a 100 ng/kg per min dose elevated RBF and GFR by 13 and 14%, respectively, while concomitantly increasing APG by 38%. At 200 ng/kg per min, galanin elevated RBF and GFR by 32 and 33%, respectively, while elevating APG by 57%. Intrarenal infusion of glucose (12.5 mg/kg per min; n = 6), reproducing the percentage rise in glucose (62%) elicited by the highest dose of galanin, elevated RBF and GFR by 20 and 23%, respectively. These data indicate that the elevated plasma glucose level, stimulated by galanin infusion, may account for about 63 and 70% of the RBF and GFR responses, respectively, elicited by galanin infusion at the 200 ng dose. The factors mediating the remaining renal hyperemia and hyperfiltration await resolution.

Influence of experimental hyperthyroidism on skeletal muscle metabolism in the rat.

PubMed

van Hardeveld, C; Kassenaar, A A

1977-05-01

In this study hind-limb perfusion was used to investigate the influence of thyroid hormones on some metabolic parameters in the skeletal muscle of the rat. Daily injection of 20 microng L-thyroxine (T4) per 100 g b. w. for a week caused a 25% increase in oxygen consumption. Further enlargement of the T4 dose had little additive effect. In the dose range 20--80 microng T4/100g b.w., no important changes occurred in lactate production or glucose consumption. Only at the highest T4 dose did the glucose consumption increase significantly. The most profound effect of T4 was on lipolysis. A daily dose of 20 microng T4/100 g b. w. gave a doubling of glycerol production rate, the maximum occuring at a dose of 40 microng T4/100 g b. w. Inactivation of the nervous system was without influence on the T4-induced increase in oxygen consumption. However, the T4-induced elevation of lipolysis disappeared after abolition of the nervous activity. This raises the possibility that the T4 effect on lipolysis in skeletal muscle is a potentiation of catecholamine effects. The T4-induced oxygen consumption increase might be dependent not on the lipolytic process but rather on other energy-consuming cell processes.

Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS

PubMed Central

Madigan, Nicolas N.; Morris, Jonathan; Jentoft, Mark; Sorenson, Eric J.; Butler, Greg; Gastineau, Dennis; Dietz, Allan; Windebank, Anthony J.

2016-01-01

Objective: To determine the safety of intrathecal autologous adipose-derived mesenchymal stromal cell treatment for amyotrophic lateral sclerosis (ALS). Methods: Participants with ALS were enrolled and treated in this phase I dose-escalation safety trial, ranging from 1 × 107 (single dose) to 1 × 108 cells (2 monthly doses). After intrathecal treatments, participants underwent standardized follow-up, which included clinical examinations, revised ALS Functional Rating Scale (ALSFRS-R) questionnaire, blood and CSF sampling, and MRI of the neuroaxis. Results: Twenty-seven patients with ALS were enrolled and treated in this study. The safety profile was positive, with the most common side effects reported being temporary low back and radicular leg pain at the highest dose level. These clinical findings were associated with elevated CSF protein and nucleated cells with MRI of thickened lumbosacral nerve roots. Autopsies from 4 treated patients did not show evidence of tumor formation. Longitudinal ALSFRS-R questionnaires confirmed continued progression of disease in all treated patients. Conclusions: Intrathecal treatment of autologous adipose-derived mesenchymal stromal cells appears safe at the tested doses in ALS. These results warrant further exploration of efficacy in phase II trials. Classification of evidence: This phase I study provides Class IV evidence that in patient with ALS, intrathecal autologous adipose-derived mesenchymal stromal cell therapy is safe. PMID:27784774

Integrated survey on toxic effects of lindane on neotropical fish: Corydoras paleatus and Jenynsia multidentata.

PubMed

Pesce, Silvia F; Cazenave, Jimena; Monferrán, Magdalena V; Frede, Silvia; Wunderlin, Daniel A

2008-12-01

We report the effect of lindane on fish experimentally exposed to lindane. Sublethal toxicity was assessed through (a) changes in histopathology; (b) the activity of GST in different organs; and (c) bioaccumulation in exposed fish. We present a survey on toxic effects of lindane at these three levels, proposing a sequence of dose-dependent effects. Physiological damage was reversible at lowest doses, but severe at the highest, including damage consistent with fibrosis in liver and karyolitic nucleus in brain of both studied species. Exposure of Jenynsia multidentata above 6 microg L(-1) caused activation a GST in liver and gills, followed by inhibition at 75 microg L(-1). Interestingly, the bioaccumulation rate was suddenly increased when GST was inhibited. Corydoras paleatus exposed to 6.0 microg L(-1) lindane did not present significant changes in GST activity; however, enzymatic inhibition was observed above 25 microg L(-1). The bioaccumulation rate in C. paleatus remained constant throughout the experiments. All in all, these results evidence that C. paleatus is more sensitive to lindane than J. multidentata.

An investigation of flat panel equipment variables on image quality with a dedicated cardiac phantom

NASA Astrophysics Data System (ADS)

Dragusin, O.; Bosmans, H.; Pappas, C.; Desmet, W.

2008-09-01

Image quality (IQ) evaluation plays a key role in the process of optimization of new x-ray systems. Ideally, this process should be supported by real clinical images, but ethical issues and differences in anatomy and pathology of patients make it impossible. Phantom studies might overcome these issues. This paper presents the IQ evaluation of 30 cineangiographic films acquired with a cardiac flat panel system. The phantom used simulates the anatomy of the heart and allows the circulation of contrast agent boluses through coronary arteries. Variables investigated with influence on IQ and radiation dose are: tube potential, detector dose, added Copper filters, dynamic density optimization (DDO) and viewing angle. The IQ evaluation consisted of scoring 4 simulated calcified lesions located on different coronary artery segments in terms of degree of visualization. Eight cardiologists rated the lesions using a five-point scale ((1) lesion not visible to (5) very good visibility). Radiation doses associated to the angiograms are expressed in terms of incident air kerma (IAK) and effective dose that has been calculated with PCXMX software (STUK, Finland) from the exposure settings assuming a standard sized patient of 70 Kg. Mean IQ scores ranged from 1.68 to 4.88. The highest IQ scores were obtained for the angiograms acquired with tube potential 80 kVp, no added Cu filters, DDO 60%, RAO and LAO views and the highest entrance detector dose that has been used in the present study, namely 0.17 μGy/im. Radiation doses (IAK ~40 mGy and effective dose of 1 mSv) were estimated for angiograms acquired at 15 frames s-1, detector field-of-view 20 cm, and a length of 5 s. The following parameters improved the IQ factor significantly: a change in tube potential from 96 to 80 kVp, detector dose from 0.10 μGy/im to 0.17 μGy/im, the absence of Copper filtration. DDO variable which is a post-processing parameter should be carefully evaluated because it alters the quality of the images independently of radiation exposure settings. The SAM anthropomorphic phantom has the advantage of visualization of stenotic lesions during the injection of a contrast agent and using an anatomical background. In the future, this phantom could potentially bridge the gap between physics tests and the clinical reality in the catheterization laboratory.

Operator Radiation and the Efficacy of Ceiling-Suspended Lead Screen Shielding during Coronary Angiography: An Anthropomorphic Phantom Study Using Real-Time Dosimeters

NASA Astrophysics Data System (ADS)

Jia, Qianjun; Chen, Ziman; Jiang, Xianxian; Zhao, Zhenjun; Huang, Meiping; Li, Jiahua; Zhuang, Jian; Liu, Xiaoqing; Hu, Tianyu; Liang, Wensheng

2017-02-01

Operator radiation and the radiation protection efficacy of a ceiling-suspended lead screen were assessed during coronary angiography (CA) in a catheterization laboratory. An anthropomorphic phantom was placed under the X-ray beam to simulate patient attenuation in eight CA projections. Using real-time dosimeters, radiation dose rates were measured on models mimicking a primary operator (PO) and an assistant. Subsequently, a ceiling-suspended lead screen was placed in three commonly used positions to compare the radiation protection efficacy. The radiation exposure to the PO was 2.3 to 227.9 (mean: 67.2 ± 49.0) μSv/min, with the left anterior oblique (LAO) 45°/cranial 25° and cranial 25° projections causing the highest and the lowest dose rates, respectively. The assistant experienced significantly less radiation overall (mean: 20.1 ± 19.6 μSv/min, P < 0.003), with the right anterior oblique (RAO) 30° and cranial 25° projections resulting in the highest and lowest exposure levels, respectively. Combined with table-side shielding, the ceiling-suspended lead screen reduced the radiation to the PO by 76.8%, 81.9% and 93.5% when placed close to the patient phantom, at the left side and close to the PO, respectively, and reduced the radiation to the assistant by 70.3%, 76.7% and 90.0%, respectively. When placed close to the PO, a ceiling-suspended lead screen provides substantial radiation protection during CA.

Pharmacogenetic approach to losartan in Marfan patients: a starting point to improve dosing regimen?

PubMed

Falvella, Felicia Stefania; Marelli, Susan; Cheli, Stefania; Montanelli, Stefano; Viecca, Federico; Salvi, Lucia; Ferrara, Alfio; Clementi, Emilio; Trifirò, Giuliana; Pini, Alessandro

2016-09-01

Losartan is under evaluation for managing Marfan patients with aortic root dilatation. Cytochrome P450 (CYP) enzymes convert losartan to E3174 active metabolite. The aim of this study is to describe the distribution of CYP2C9*2, CYP2C9*3, CYP3A4*22 and CYP3A5*3 defective alleles, according to losartan tolerance in paediatric Marfan patients. We genotyped 53 paediatric Marfan patients treated with losartan. The rate of aortic root dilatation was evaluated using the delta z-score variation. Differences in tolerated losartan daily doses with respect to CYP metabolic classes were assessed through the Kruskal-Wallis test. The losartan daily dose spans from 0.16 to 2.50 mg/kg (median 1.10 mg/kg). As we expect from the pharmacokinetics pathway, we observe highest tolerated dose in CYP2C9 poor metabolisers (median 1.50 mg/kg, interquartile range 1.08-1.67 mg/kg); however, this difference is not statistically significant. The optimal dose of angiotensin receptor blocker is not known, and no data are available about losartan pharmacogenetic profile in Marfan syndrome; we have proposed a strategy to tackle this issue based on evaluating the major genetic polymorphisms involved in the losartan conversion into active carboxylic acid metabolite. Further studies are needed to support the use of genetic polymorphisms as predictors of the right dose of losartan.

[Personal dose monitoring of radiation workers in medical institutions at the municipal level and below in a city from 2011 to 2014].

PubMed

Wang, C; Mo, S F; Zhang, J B; Li, J R; Huang, R L; Tan, H Y

2017-08-20

Objective: To determine the personal dose level of radiation workers in medical institutions at the municipal level and below in a city, and to provide a scientific support for strengthening the radiation protection in the city's medical institutions. Methods: Information of the successful applicants for the "Radiation Worker Permit" from 174 medical institutions at the municipal level and below was collected from October 1, 2011 to December 31, 2014. The annual effective dose was calculated based on the personal dose monitoring report, and indicators including sex, permit application time, hospital level, type of occupational radiation, length of radiation work, blood test, and micronucleated lymphocyte rate were analyzed. Results: Of the 1 143 radiation worker permit applications submitted by medical institutions the municipal level and below in this city from 2011 to 2014, 1 123 provided at least one personal dose monitoring report. The annual effective dose of the radiation workers was 0-4.76 mSv (mean 0.31±0.40 mSv) , and the collective annual effective dose was 351.96 mSv. The annual effective dose was significantly different between radiation workers with different times of permit application, hospital levels, and types of occupational radiation ( P <0.05) . Interventional radiology workers had the highest annual effective dose (0.63 mSv) , and annual effective dose was significantly different between interventional radiology workers with different lengths of radiation work ( H =10.812, P <0.05) . Conclusion: The personal radiation dose of radiation workers in medical institutions at the municipal level and below in this city is maintained at a relatively low level, suggesting that the occupational environment is relatively safe for these workers. However, more focus should be placed on clinical interventional radiology workers.

Antifungal effect of some plant extracts against factors wheat root rot

NASA Astrophysics Data System (ADS)

Atmaca, Sevim; Şimşek, Şeyda; Denek, Yunus Emre

2017-04-01

Methanol leaf extracts of Humulus lupulus L. and Achillea millefolium L. were evaluated for antifungal activity against economically important phytopathogenic fungi including Fusarium culmorum (W. G. Smith) Sacc. The final concentrations of the methanol extracts obtained from the plants were added to the Potato Dextrose Agar (PDA) at 1%, 2%, 4% and 8% doses. Mycelial disks of pathogens (6 mm in diameter) removed from the margins of a 7 days old culture were transferred to PDA media containing the plant extracts at tested concentrations. Four replicates were used per treatment. For each plant extract and concentration, inhibition of radial growth compared with the untreated control was calculated after 7 days of incubation at 24±1°C, in the dark. Extracts H. lupulus and A. millefolium inhibited the mycelial growth of F. culmorum of mycelial growth of 8% dose of the pathogens by 92.77% and 69.83%, respectively. It has been observed that the antifungal effect of the extracts increases with dose increase. As a result, at least micelle growth and the highest percent inhibition rate were obtained at 8% dose of the extract H. lupulus. H. lupulus extract can be used as a biological preparation.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PubMed

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O'Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-10-01

To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

A real-time regional adaptive exposure method for saving dose-area product in x-ray fluoroscopy

PubMed Central

Burion, Steve; Speidel, Michael A.; Funk, Tobias

2013-01-01

Purpose: Reduction of radiation dose in x-ray imaging has been recognized as a high priority in the medical community. Here the authors show that a regional adaptive exposure method can reduce dose-area product (DAP) in x-ray fluoroscopy. The authors' method is particularly geared toward providing dose savings for the pediatric population. Methods: The scanning beam digital x-ray system uses a large-area x-ray source with 8000 focal spots in combination with a small photon-counting detector. An imaging frame is obtained by acquiring and reconstructing up to 8000 detector images, each viewing only a small portion of the patient. Regional adaptive exposure was implemented by varying the exposure of the detector images depending on the local opacity of the object. A family of phantoms ranging in size from infant to obese adult was imaged in anteroposterior view with and without adaptive exposure. The DAP delivered to each phantom was measured in each case, and noise performance was compared by generating noise arrays to represent regional noise in the images. These noise arrays were generated by dividing the image into regions of about 6 mm2, calculating the relative noise in each region, and placing the relative noise value of each region in a one-dimensional array (noise array) sorted from highest to lowest. Dose-area product savings were calculated as the difference between the ratio of DAP with adaptive exposure to DAP without adaptive exposure. The authors modified this value by a correction factor that matches the noise arrays where relative noise is the highest to report a final dose-area product savings. Results: The average dose-area product saving across the phantom family was (42 ± 8)% with the highest dose-area product saving in the child-sized phantom (50%) and the lowest in the phantom mimicking an obese adult (23%). Conclusions: Phantom measurements indicate that a regional adaptive exposure method can produce large DAP savings without compromising the noise performance in the image regions with highest noise. PMID:23635281

Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA.

PubMed

Dayan, Gustavo H; Thakur, Manoj; Boaz, Mark; Johnson, Carol

2013-10-17

A candidate recombinant, live-attenuated, CYD tetravalent dengue vaccine (CYD-TDV) has recently demonstrated immunogenicity, efficacy and good tolerability. This study was performed to evaluate three CYD-TDV formulations in adults. This was a randomized, double-blind, multicenter, phase II trial. The vaccine formulations were: CYD-TDV 5555 (≈5log10 tissue culture infectious dose 50% [TCID50] of serotypes 1-4); CYD-TDV 5553 (≈5log10 TCID50 of serotypes 1-3 and ≈3log10 TCID50 of serotype 4); and CYD-TDV 4444 (≈4log10 TCID50 of serotypes 1-4). Vaccinations were administered at 0, 6 and 12 months. Immunogenicity was assessed using the plaque reduction neutralization test. In total, 260 individuals were enrolled. The 5555 formulation elicited a superior serotype 4 response versus the 5553 formulation, with seropositivity rates of 89.7% and 58.3%, respectively, after the second dose (between-group difference 31.4%; 95% confidence interval 18.2-43.2). After each of the three doses, seropositivity rates for serotypes 1-3 were numerically highest with CYD-TDV 5553 and lowest with the 4444 formulation; seropositivity rates for serotype 4 were similar with the 5555 and 4444 formulations, and much lower among recipients of CYD-TDV 5553. Geometric mean titers followed the same pattern as that seen with seropositivity rates. Safety/reactogenicity results were similar for all three vaccine formulations, although the percentage of participants reporting solicited injection site reactions was lower with CYD-TDV 4444 than with the other two formulations. All serious adverse events were unrelated to vaccination. Reducing the dose of serotype 4 antigen (5553 formulation) creates an imbalance in the immune response to CYD-TDV. Immune responses to CYD-TDV 5555 were slightly higher than to the 4444 formulation. Development of CYD-TDV 5555 has subsequently been pursued. Copyright © 2013 Elsevier Ltd. All rights reserved.

75 FR 19272 - Thifensulfuron methyl; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-14

... background exposure level). A short and intermediate-term adverse effect was identified; however... of small renal papillae (only at the highest dose level). Thifensulfuron methyl is classified as... only at the mid-level dose of 177 mg/kg. The lack of response at the high-level dose, the occurrence in...

Direct-Write Fabrication of Cellulose Nano-Structures via Focused Electron Beam Induced Nanosynthesis

PubMed Central

Ganner, Thomas; Sattelkow, Jürgen; Rumpf, Bernhard; Eibinger, Manuel; Reishofer, David; Winkler, Robert; Nidetzky, Bernd; Spirk, Stefan; Plank, Harald

2016-01-01

In many areas of science and technology, patterned films and surfaces play a key role in engineering and development of advanced materials. Here, we introduce a new generic technique for the fabrication of polysaccharide nano-structures via focused electron beam induced conversion (FEBIC). For the proof of principle, organosoluble trimethylsilyl-cellulose (TMSC) thin films have been deposited by spin coating on SiO2 / Si and exposed to a nano-sized electron beam. It turns out that in the exposed areas an electron induced desilylation reaction takes place converting soluble TMSC to rather insoluble cellulose. After removal of the unexposed TMSC areas, structured cellulose patterns remain on the surface with FWHM line widths down to 70 nm. Systematic FEBIC parameter sweeps reveal a generally electron dose dependent behavior with three working regimes: incomplete conversion, ideal doses and over exposure. Direct (FT-IR) and indirect chemical analyses (enzymatic degradation) confirmed the cellulosic character of ideally converted areas. These investigations are complemented by a theoretical model which suggests a two-step reaction process by means of TMSC → cellulose and cellulose → non-cellulose material conversion in excellent agreement with experimental data. The extracted, individual reaction rates allowed the derivation of design rules for FEBIC parameters towards highest conversion efficiencies and highest lateral resolution. PMID:27585861

[Cerebral metabolism and permeability of the hemato-encephalic barrier in an experimental model for brain radiotherapy].

PubMed

Cicciarello, R; Russi, E; Albiero, F; Mesiti, M; Torre, E; D'Aquino, A; Raffaele, L; Bertolani, S; D'Avella, D

1990-11-01

Whole brain irradiation (WBR) can produce acute and chronic neurological adverse effects, which are usually divided into acute, early delayed and late delayed reactions according to the time of onset. To assess the impact of WBR on brain functional parameters during the early-delayed phase, we employed the [14C]-2-deoxyglucose (2-DG) and the [14C]-alfa-aminoisobutyric (AIB) acid quantitative autoradiographic techniques to study local cerebral glucose utilization and blood-brain barrier permeability, respectively. Sprague-Dowley albino rats were exposed to conventional fractionation (200 Gy/day 5 days a week) for a total dose of 4000 Gy. Experiments were made 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. As a rule, brain areas with the highest basal metabolic rates showed the highest percentage drop in glucose utilization. Changes in blood-brain barrier function, as assessed by an increased transcapillary transport of AIB, were also demonstrated in specific brain regions. This study illustrates how moderate doses of WBR induce well-defined changes in brain metabolism and BBB function, which are possibly involved in the pathogenesis of the early-delayed radiation-induced cerebral dysfunction in humans.

Predesigned labels to prevent medication errors in hospitalized patients: a quasi-experimental design study.

PubMed

Morales-González, María Fernanda; Galiano Gálvez, María Alejandra

2017-09-08

Our institution implemented the use of pre-designed labeling of intravenous drugs and fluids, administration routes and infusion pumps of to prevent medication errors. To evaluate the effectiveness of predesigned labeling in reducing medication errors in the preparation and administration stages of prescribed medication in patients hospitalized with invasive lines, and to characterize medication errors. This is a pre/post intervention study. Pre-intervention group: invasively administered dose from July 1st to December 31st, 2014, using traditional labeling (adhesive paper handwritten note). Post-intervention group: dose administered from January 1st to June 30th, 2015, using predesigned labeling (labeling with preset data-adhesive labels, color- grouped by drugs, labels with colors for invasive lines). Outcome: medication errors in hospitalized patients, as measured with notification form and record electronics. Tabulation/analysis Stata-10, with descriptive statistics, hypotheses testing, estimating risk with 95% confidence. In the pre-intervention group, 5,819 doses of drugs were administered invasively in 634 patients. Error rate of 1.4 x 1,000 administrations. The post-intervention group of 1088 doses comprised 8,585 patients with similar routes of administration. The error rate was 0.3 x 1,000 (p = 0.034). Patients receiving medication through an invasive route who did not use predesigned labeling had 4.6 times more risk of medication error than those who had used predesigned labels (95% CI: 1.25 to 25.4). The adult critically ill patient unit had the highest proportion of medication errors. The most frequent error was wrong dose administration. 41.2% produced harm to the patient. The use of predesigned labeling in invasive lines reduces errors in medication in the last two phases: preparation and administration.

Nanosuspension for the delivery of a poorly soluble anti-cancer kinase inhibitor.

PubMed

Danhier, Fabienne; Ucakar, Bernard; Vanderhaegen, Marie-Lyse; Brewster, Marcus E; Arien, Tina; Préat, Véronique

2014-09-01

We hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG₇₅₀-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the nano-formulations presented a size below 200 nm. Injections of the highest possible dose of the three nano-formulations did not induce any side effects in mice. In contrast, the maximum tolerated dose of the control Captisol solution was 20-fold lower than its highest possible dose. The highest regrowth delay of A-431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension, administered intravenously, at a dose of 650 mg/kg. After intravenous and oral administration, the AUC₀₋∞ of MTKi-327 nanosuspension was 2.4-fold greater than that of the Captisol solution. Nanosuspension may be considered as an effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327 maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327, (iii) its ability to enhance the administered dose and (iv) its higher efficacy. Copyright © 2014 Elsevier B.V. All rights reserved.

Randomized, placebo-controlled trial to assess the safety and immunogenicity of an adenovirus type 35-based circumsporozoite malaria vaccine in healthy adults.

PubMed

Creech, C Buddy; Dekker, Cornelia L; Ho, Dora; Phillips, Shanda; Mackey, Sally; Murray-Krezan, Cristina; Grazia Pau, Maria; Hendriks, Jenny; Brown, Valerie; Dally, Leonard G; Versteege, Isabella; Edwards, Kathryn M

2013-12-01

Malaria results in over 650,000 deaths each year; thus, there is an urgent need for an effective vaccine. Pre-clinical studies and recently reported human trials suggest that pre-erythrocytic stage vaccines can provide protection against infection. A Phase 1, randomized, placebo-controlled, dose-escalation study was conducted with a vaccine composed of a replication-deficient adenovirus-35 backbone with P. falciparum circumsporozoite (CS) surface antigen (Ad35.CS.01). Healthy adult subjects received three doses of 10 (8), 10 (9), 10 (10), or 10 (11) vp/mL Ad35.CS.01 vaccine or saline placebo intramuscularly at 0, 1, and 6-mo intervals. Adverse events were assessed and anti-CS antibody responses were determined by ELISA. Seventy-two individuals were enrolled, with age, gender, and ethnicity similar across each study arm. While the vaccine was generally well tolerated, adverse events were more frequent in the highest dose groups (10 (10) and 10 (11) vp/mL). More robust humoral responses were also noted at the highest doses, with 73% developing a positive ELISA response after the three dose series of 10 (11) vp/mL. The Ad35.CS.01 vaccine was most immunogenic at the highest dosages (10 (10) and 10 (11) vp/mL). Reactogenicity findings were more common after the 10 (11) vp/mL dose, although most were mild or moderate in nature and resolved without therapy.

Scattered radiation doses absorbed by technicians at different distances from X-ray exposure: Experiments on prosthesis.

PubMed

Chiang, Hsien-Wen; Liu, Ya-Ling; Chen, Tou-Rong; Chen, Chun-Lon; Chiang, Hsien-Jen; Chao, Shin-Yu

2015-01-01

This work aimed to investigate the spatial distribution of scattered radiation doses induced by exposure to the portable X-ray, the C-arm machine, and to simulate the radiologist without a shield of lead clothing, radiation doses absorbed by medical staff at 2 m from the central exposure point. With the adoption of the Rando Phantom, several frequently X-rayed body parts were exposed to X-ray radiation, and the scattered radiation doses were measured by ionization chamber dosimeters at various angles from the patient. Assuming that the central point of the X-ray was located at the belly button, five detection points were distributed in the operation room at 1 m above the ground and 1-2 m from the central point horizontally. The radiation dose measured at point B was the lowest, and the scattered radiation dose absorbed by the prosthesis from the X-ray's vertical projection was 0.07 ±0.03 μGy, which was less than the background radiation levels. The Fluke biomedical model 660-5DE (400 cc) and 660-3DE (4 cc) ion chambers were used to detect air dose at a distance of approximately two meters from the central point. The AP projection radiation doses at point B was the lowest (0.07±0.03 μGy) and the radiation doses at point D was the highest (0.26±0.08 μGy) .Only taking the vertical projection into account, the radiation doses at point B was the lowest (0.52 μGy), and the radiation doses at point E was the highest (4 μGy).The PA projection radiation at point B was the lowest (0.36 μGy) and the radiation doses at point E was the highest(2.77 μGy), occupying 10-32% of the maximum doses. The maximum dose in five directions was nine times to the minimum dose. When the PX and the C-arm machine were used, the radiation doses at a distance of 2 m were attenuated to the background radiation level. The radiologist without a lead shield should stand at point B of patient's feet. Accordingly, teaching materials on radiation safety for radiological interns and clinical technicians were formulated.

A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil.

PubMed

Olliaro, Piero L; Vaillant, Michel T; Belizario, Vincente J; Lwambo, Nicholas J S; Ouldabdallahi, Mohamed; Pieri, Otavio S; Amarillo, Maria L; Kaatano, Godfrey M; Diaw, Mamadou; Domingues, Analucia C; Favre, Tereza C; Lapujade, Olivier; Alves, Fabiana; Chitsulo, Lester

2011-06-01

Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n  =  428) or 60 mg/kg (n  =  428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR  =  0.78, 95% CI  = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries.

Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

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

Kubicek, Gregory J.; Werner-Wasik, Maria; Machtay, Mitchell

Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m{sup 2}/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m{sup 2} starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributablemore » to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m{sup 2}/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m{sup 2}) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.« less

Effective dose in the manufacturing process of rutile covered welding electrodes.

PubMed

Herranz, M; Rozas, S; Pérez, C; Idoeta, R; Núñez-Lagos, R; Legarda, F

2013-03-01

Shielded metal arc welding using covered electrodes is the most common welding process. Sometimes the covering contains naturally occurring radioactive materials (NORMs). In Spain the most used electrodes are those covered with rutile mixed with other materials. Rutile contains some detectable natural radionuclides, so it can be considered a NORM. This paper mainly focuses on the use of MCNP (Monte Carlo N-Particle Transport Code) as a predictive tool to obtain doses in a factory which produces this type of electrode and assess the radiological impact in a specific facility after estimating the internal dose.To do this, in the facility, areas of highest radiation and positions of workers were identified, radioactive content of rutile and rutile covered electrodes was measured, and, considering a worst possible scenario, external dose at working points has been calculated using MCNP. This procedure has been validated comparing the results obtained with those from a pressurised ionisation chamber and TLD dosimeters. The internal dose has been calculated using DCAL (dose and risk calculation). The doses range between 8.8 and 394 μSv yr(-1), always lower than the effective dose limit for the public, 1 mSv yr(-1). The highest dose corresponds to the mixing area.

The selection of light emitting diode irradiation parameters for stimulation of human mesenchymal stem cells proliferation

NASA Astrophysics Data System (ADS)

Lewandowski, Rafał; Trafny, ElŻbieta A.; Stepińska, Małgorzata; Gietka, Andrzej; Kotowski, Paweł; Dobrzyńska, Monika; Łapiński, Mariusz P.

2016-12-01

Human mesenchymal stem cells (hMSCs) with their vast differentiation potential are very useful for cell-based regenerative medicine. To achieve sufficient numbers of cells for tissue engineering, many different methods have been used to reach the effective increase of cell proliferation. Low-energy red light provided by light emitting diodes (LEDs) have been recently introduced as a method that promoted biomodulation and proliferation of hMSCs in vitro. The purpose of this study was to find the optimum stimulatory dosimetric parameters of LED (630 nm) irradiation on the hMSCs proliferation. The energy density was 2, 3, 4, 10, 20 J/cm2 and the power density used was 7, 17 or 30 mW/cm2. Human MSCs were irradiated with single or triple exposures daily at room temperature and the cell proliferation rate was evaluated during nine days after irradiation. The results showed that after irradiation 4 J/cm2 and 17 mW/cm2 at a single dose the proliferation rate of hMSCs increased on day 5 and 9 (13% and 7%, respectively) when compared to nonirradiated cells. However, triple LED irradiation under the same parameters resulted in the decline in the cell proliferation rate on day 5, but the proliferation rate was at the same level on day 9, when compared with the cell proliferation after irradiation with a single dose. The effect of a single dose irradiation with 4 J/cm2 and 17 mW/cm2 on the proliferation of cells was the highest when the cells were irradiated in phosphate-buffered saline (PBS) instead of MSCGM culture medium.

[Intra-amniotic administration of prostaglandin F 2 alpha, 12-methyl-prostaglandin F 2 alpha and hypertonic sodium chloride solution for induction of abortion in second-trimester pregnancy].

PubMed

Persianinov, L S; Chernukha, E A

1975-01-01

The authors had performed comperative studies of the effect of the induction of abortion in late pregnancy according to the medical indications by intra-amniotic injection of 20% hypertonic NaCl saline in 26 pregnant patients, of 25 mg prostaglandin F2alpha with 6 hours' intervals in 25 patients, a single dose injection of 40 mg PGF2alpha in 27 cases and single dose injection of 2,5 mg 15-me-PGF2alpha given to 25 patients. The highest success rate was obtained with the single dose injection of 2,5 mg 15-me-PGF2alpha and the lowest success rate was obtained with 25 mg prostaglandin F2alpha with 6 hours' intervals. Despite of rather high procentage of success rate in using the hypertonic NaCl saline, this method is more dangerous in the moment of the injection of saline and complications during the abortion (water intoxication, necrosis of tissue, coagulation defects and other). The most frequently incountered side-effects in using PGs were vomiting and diarhea. Histologic examinations of the placenta revealed massive bleedings, at frequency rate being the same for prostaglandins and the hypertonic saline. The degree of isoimmunisation was lower with prostaglandins than with hypertonic NaCl saline, despite of the late dates of pregnancy termination. The intro-amniotic injection of the small volume solution of 15-me-PGF2alpha or PGF2alpha is more simpler and easier from the technical point of view than any methodic recommended for using saline and at the same time it is more effective.

Understanding flucloxacillin prescribing trends and treatment non-response in UK primary care: a Clinical Practice Research Datalink (CPRD) study

PubMed Central

Francis, Nick A.; Hood, Kerenza; Lyons, Ronan; Butler, Christopher C.

2016-01-01

Objectives The volume of prescribed antibiotics is associated with antimicrobial resistance and, unlike most other antibiotic classes, flucloxacillin prescribing has increased. We aimed to describe UK primary care flucloxacillin prescribing and factors associated with subsequent antibiotic prescribing as a proxy for non-response. Patients and methods Clinical Practice Research Datalink patients with acute prescriptions for oral flucloxacillin between January 2004 and December 2013, prescription details, associated Read codes and patient demographics were identified. Monthly prescribing rates were plotted and logistic regression identified factors associated with having a subsequent antibiotic prescription within 28 days. Results 3 031 179 acute prescriptions for 1 667 431 patients were included. Average monthly prescription rates increased from 4.74 prescriptions per 1000 patient-months in 2004 to 5.74 (increase of 21.1%) in 2013. The highest prescribing rates and the largest increases in rates were seen in older adults (70+ years), but the overall increase in prescribing was not accounted for by an ageing population. Prescribing 500 mg tablets/capsules rather than 250 mg became more common. Children were frequently prescribed low doses and small volumes (5 day course) and prescribing declined for children, including for impetigo. Only 4.2% of new prescriptions involved co-prescription of another antibiotic. Age (<5 and ≥60 years), diagnosis of ‘cellulitis or abscess’ or no associated code, and 500 mg dose were associated with a subsequent antibiotic prescription, which occurred after 17.6% of first prescriptions. Conclusions There is a need to understand better the reasons for increased prescribing of flucloxacillin in primary care, optimal dosing (and the need to co-prescribe other antibiotics) and the reasons why one in five patients are prescribed a further antibiotic within 4 weeks. PMID:27090629

Irrigation dose and plant density affect the volatile composition and sensory quality of dill (Anethum graveolens L.).

PubMed

El-Zaeddi, Hussein; Martínez-Tomé, Juan; Calín-Sánchez, Ángel; Burló, Francisco; Carbonell-Barrachina, Ángel A

2017-01-01

Two independent field experiments were carried out to investigate the influence of (i) three irrigation treatments (ID0 = 1585 m 3 ha -1 , considered as a control; ID1 = 1015 m 3 ha -1 ; and ID2 = 2180 m 3 ha -1 ) and (ii) three plant density treatments (PD0 = 5.56 plants m -2 , considered as a control; PD1 = 4.44 plants m -2 ; and PD2 = 7.41 plants m -2 ) on the production, volatile composition of essential oil, and sensory quality of dill. The highest plant yield was obtained with intermediate conditions of both irrigation dose (ID0) and plant density (PD0). The main compounds of the essential oil were α-phellandrene, dill ether and β-phellandrene. The highest irrigation dose (ID2) produced the highest concentrations of most of the main compounds: α-phellandrene (49.5 mg per 100 g), β-phellandrene (6.89 mg per 100 g) and limonene (2.49 mg per 100 g). A similar pattern was found for the highest plant density (PD2): α-phellandrene (71.0 mg per 100 g), dill ether (16.7 mg per 100 g) and β-phellandrene (9.70 mg per 100 g). The use of descriptive sensory analysis helped in reaching a final decision, and the dill plants with the highest sensory quality were those of the ID2 and PD0 treatments. The final recommendation is to use the irrigation dose ID2 and the plant density PD2 if the objective is to produce dill samples with the highest aromatic and sensory quality; however, if the only objective is to produce high amounts of dill, the best options are ID0 and PD0. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Drug elution from high-dose antibiotic-loaded acrylic cement: a comparative, in vitro study.

PubMed

Gasparini, Giorgio; De Gori, Marco; Calonego, Giovanni; Della Bora, Tommaso; Caroleo, Benedetto; Galasso, Olimpio

2014-11-01

High-dose antibiotic-loaded acrylic cement (ALAC) is used for managing peri-prosthetic joint infections (PJIs). The marked increase in resistant high-virulence bacteria is drawing the attention of physicians toward alternative antimicrobial formulations loaded into acrylic bone cement. The aim of this in vitro study was to determine the elution kinetics of 14 different high-dose ALACs. All ALAC samples showed a burst release of antibiotics in the first hour, progressively decreasing over time, and elution curves strictly adhered to a nonlinear regression analysis formula. Among aminoglycosides, commonly seen as the most appropriate antibiotics to be loaded into the bone cement, the highest elution rate was that of tobramycin. Among the glycopeptides, a class of antibiotics that should be considered to treat PJIs because of the prevalence of aminoglycoside resistance, vancomycin showed better elution than teicoplanin. Clindamycin, which can be associated with aminoglycosides to prepare ALACs and represents a useful option against the most common pathogens responsible for PJIs, showed the highest absolute and relative elutions among all the tested formulations. A noticeable elution was also detected for colistin, an antibiotic of last resort for treating multidrug-resistant bacteria. The current study demonstrates theoretical advantages in the preparation of ALAC for some antibiotics not routinely used in the clinical setting for PJIs. The use of these antibiotics based on the infecting bacteria sensitivity may represent a useful option for physicians to eradicate PJIs. In vivo testing should be considered in the future to confirm the results of this study. Copyright 2014, SLACK Incorporated.

Fabrication and characterization of bolus material using polydimethyl-siloxane

NASA Astrophysics Data System (ADS)

Wiratma Jaya, Gede; Sutanto, Heri

2018-01-01

Bolus has been used in radiotherapy to reduce tissue harm and to increase the superficial dose for skin cancer treatment. Commonly, a bolus is made of melamine in several hospitals. In this research, polydimethyl-siloxane (PDMS) material was used for bolus fabrication. The aims of the study are to investigate bolus density, percentage surface dose and its structural strength for each various composition. In bolus preparation, bolus material used composition variation between PDMS volume and catalyst volume. Composition variation were 20:1, 22:1, 24:1, 26:1, 28:1, 30:1 and 32:1. PDMS and catalyst were mixed by chemical solution deposition method. Bolus was molded by using glass cast with the size of 10 × 10 × 0.5 cm3. Bolus density was analyzed by mass per volume equation, for bolus radiation was examined by the linear accelerator using two electron energy (5 and 7 MeV) and bolus strain and tensile strength were examined by Brookfield CT 3 machine. The results of bolus density were similar with soft tissue density, while the lowest and highest density each variation are 22:1 and 28:1. In general, the use of bolus has increased the surface dose. Percentage of surface dose at 5 MeV energy is higher than 7 MeV energy. The highest percentage of surface dose at 5 MeV energy with 0.5 and 1.0 cm bolus thickness was achieved at composition of 32:1. For strain and tensile strength result, the lowest and highest strain each variation are 22:1 and 28:1, then the lowest and highest tensile strength each variation are 32:1 and 28:1. These results is important to select composition material for bolus fabrication in radiotherapy treatment.

Pyrene fate affected by humic acid amendment in soil slurry systems.

PubMed

Liang, Yanna; Sorensen, Darwin L; McLean, Joan E; Sims, Ronald C

2008-09-10

Humic acid (HA) has been found to affect the solubility, mineralization, and bound residue formation of polycyclic aromatic hydrocarbons (PAHs). However, most of the studies on the interaction between HA and PAH concentrated on one or two of the three phases. Few studies have provided a simple protocol to demonstrate the overall effects of HA on PAH distribution in soil systems for all three phases. In this study, three doses of standard Elliott soil HA (ESHA), 15, 187.5, and 1,875 mug ESHA/g soil slurry, were amended to soil slurry systems. 14C-pyrene was added to the systems along with non-radiolabeled pyrene; 14C and 14CO2 were monitored for each system for a period of 120 days. The highest amendment dose significantly increased the 14C fraction in the aqueous phase within 24 h, but not after that time. Pyrene mineralization was significantly inhibited by the highest dose over the 120-day study. While organic solvent extractable 14C decreased with time in all systems, non-extractable or bound 14C was significantly enhanced with the highest dose of ESHA addition. Amendment of the highest dose of ESHA to pyrene contaminated soil was observed to have two major functions. The first was to mitigate CO2 production significantly by reducing 14CO2 from 14C pyrene mineralization. The second was to significantly increase stable bound 14C formation, which may serve as a remediation end point. Overall, this study demonstrated a practical approach for decontamination of PAH contaminated soil. This approach may be applicable to other organic contaminated environments where active bioremediation is taking place.

Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by 0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P < 0.005) but did not change mean arterial blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.

Fundamental research on the action mechanism of the 800 nm semiconductor laser on skin blackheads and coarse pores.

PubMed

Lin, Jie; Jing, Li; Zhu, Hao; Dong, Fu-Sheng

2017-01-01

The aim of the study was to determine the mechanism of action of the 800 nm semiconductor laser on skin blackheads and coarse pores. A total of 24 healthy purebred short-haired male guinea pigs, weighing 350-400 g, were selected and smeared with 0.5 ml coal tar suspension evenly by injector once daily. Treatment was continued for 14 days to form an experimental area of 8×3 cm on the back of the guinea pigs. The animals were divided into the following groups: Normal control group (NC), low-dose laser treatment group (L-LS), high-dose laser treatment group (H-LS), and Q-switched Nd:YAG treatment group (QC). Samples were extracted 1, 7 and 14 days after surgery and hematoxylin and eosin staining was used to identify the following: Epidermis, dermis, sebaceous gland change and hair follicle damage; the expression of proliferating cell nuclear antigen (PCNA) of sebaceous gland cells using immunohistochemistry; sebaceous gland cell apoptosis using TUNEL; and the protein expression of caspase-3, Bax and Bcl-2 using western blot analysis. With the extension of time, we observed inflammatory cell infiltration, an increase in hair follicle distortion and necrosis of the surrounding hair follicles. The expression levels of PCNA of the L-LS, H-LS and QC groups decreased with time. Regarding the respective time points, the NC group was highest, the L-LS and H-LS groups were next highest and the H-LS group was lowest. The difference was statistically significant (P<0.05). The apoptotic rate of the L-LS, H-LS and QC groups increased with time. With regard to the respective time points, the NC group was lowest, the L-LS and QC groups were next lowest and the H-LS group was highest. The difference was statistically significant (P<0.05). The protein expression of caspase-3, Bax and Bcl-2 of the L-LS, H-LS and QC groups increased with time. Regarding the respective time points, caspase-3 and Bax protein expression of the NC group was lowest, the L-LS and QC groups were next lowest and the H-LS group was highest. Bcl-2 protein expression of the NC group was highest, protein expression of the NC group was next highest and the H-LS group was lowest. The difference was statistically significant (P<0.05). In conclusion, the low-dose 800 nm semiconductor laser is an effective treatment on skin blackheads and coarse pores, and promotes hair follicle cell apoptosis without reducing the expression of PCNA.

Effects of prolonged daily low level mercuric chloride dosing in a horse

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

Roberts, M.C.; Seawright, A.A.

1978-12-01

Relatively few of the signs hitherto accepted as being consistent with chronic inorganic mercury intoxication were exhibited by a horse exposed to 31.3 g inorganic mercury (dose rate 0.4 mg/kg) given as mercuric chloride over 23.5 weeks. Clinical features included poor appetite, weight loss, debility, dullness, transient diarrhea and polydipsia, with little impairment of functional renal capacity. Limited degenerative changes were seen in the renal tubules. Edema and a mild inflammatory infiltrate of predominantly the mucosa and submucosa caused marked thickening of the lower alimentary tract. An approximate mean plasma inorganic mercury concentration of 400 ng/ml was quickly reached andmore » maintained. The kidneys had the highest tissue mercury content, almost 10 times greater than the liver and over 70 times that found in the intestinal mucosa and the dorsal root ganglia. 18 references, 6 figures.« less

Ovulation induction in polycystic ovary syndrome.

PubMed

Tanbo, Tom; Mellembakken, Jan; Bjercke, Sverre; Ring, Eva; Åbyholm, Thomas; Fedorcsak, Peter

2018-06-11

The objective of this narrative review is to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight PCOS patients the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without side effects in the doses recommended, may be suggested. Additional first line medical alternatives include insulin sensitizers, selective estrogen receptor modulators and aromatase inhibitors. Of these, the aromatase inhibitor letrozole and the combination of clomiphene citrate and metformin have the highest rates of ovulation and live birth. Second line treatments are ovarian electrocautery and low-dose follicle stimulating hormone stimulation. Controlled ovarian stimulation with in vitro fertilization, should be considered the last option since it carries a significant risk of ovarian hyperstimulation syndrome in patients with PCOS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

In vitro gas production of foliage from three browse tree species treated with different dose levels of exogenous fibrolytic enzymes.

PubMed

López, D; Vázquez-Armijo, J F; López-Villalobos, N; Lee-Rangel, H A; Salem, A Z M; Borquez-Gastelum, J L; Domínguez-Vara, I A; Rojo-Rubio, R

2016-10-01

The aim of this study was to evaluate the effect of different dose levels of exogenous fibrolytic enzymes (EFE) on in vitro ruminal fermentation kinetics and energy utilization of foliages from three browse trees (Pithecellobium dulce, Heliocarpus velutinus and Guazuma ulmifolia). Mixture of EFE product was added to the leaves of the three browse tree species at three dose levels: 0 (control), 3.5 and 7.0 mg/g of DM. Chemical composition of the foliages, including plant secondary metabolites such as total phenolics (TP), saponins (SAP) and aqueous fraction (AF), was determined. In addition, in vitro assaying of ruminal gas production kinetics was determined for the three browse three foliages treated with EFE. P. dulce had the highest crude protein content (p < 0.05), whereas G. ulmifolia had the highest content of neutral detergent fibre and SAP (p < 0.05) and H. velutinus had the lowest content of TP (p < 0.05). The interaction between tree species and dose level of EFE was significant (p < 0.05) for gas production (GP) at 24 h of incubation, parameters b and c of the accumulated GP curve, short-chain fatty acids (SCFA) and metabolizable energy (ME). The lowest (p < 0.01) extent of accumulated GP as well as the b and c values occurred in G. ulmifolia at 0 mg EFE/g DM. P. dulce had the highest (p < 0.05) values for ME and SCFA at the highest dose of EFE. Tree species and dose level had significant (p < 0.05) effects on all parameters describing in vitro ruminal fermentation kinetics and energy utilization. Addition of EFE improved the fermentation kinetics of the browse species considered in this study. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Dose-rate effects on the radiation-induced oxidation of electric cable used in nuclear power plants

NASA Astrophysics Data System (ADS)

Reynolds, A. B.; Bell, R. M.; Bryson, N. M. N.; Doyle, T. E.; Hall, M. B.; Mason, L. R.; Quintric, L.; Terwilliger, P. L.

1995-01-01

Dose-rate effects were measured for typical ethylene propylene rubber (EPR) and crosslinked polyethylene (XLPE) electric cable used in nuclear power plants. The radiation source was the 60Co Irradiation Facility at the University of Virginia. Dose rates were varied from 5 Gy/h to 2500 Gy/h. It was found that there is little or no dose-rate effect at low doses for four of the five EPR cable products tested from 2500 Gy/h down to dose rates of 5 Gy/h but perhaps a small dose-rate effect at high doses for dose rates above 340 Gy/h. A small dose-rate exists for the fifth EPR above 340 Gy/h at all doses. A dose-rate effect exists above 40 Gy/h for two of the three XLPE cable products tested, but there is no dose-rate for these XLPE's between 40 Gy/h and 5 Gy/h. These results indicate that the dose-rate effects observed are due to oxygen diffusion effects during heterogeneous aging and suggest that there is no dose-rate effect for either EPR or XLPE during homogeneous aging.

Maternal and developmental toxicity of ayahuasca in Wistar rats.

PubMed

Oliveira, Carolina Dizioli Rodrigues; Moreira, Camila Queiroz; de Sá, Lilian Rose Marques; Spinosa, Helenice de Souza; Yonamine, Mauricio

2010-06-01

Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent.

Results from the first five years of radiation exposure monitoring aboard the ISS

NASA Astrophysics Data System (ADS)

Golightly, M.; Semones, E.; Shelfer, T.; Johnson, S.; Zapp, N.; Weyland, M.

NASA uses a variety of radiation monitoring devices aboard the International Space Station as part of its space flight radiation health program. This operational monitoring system consists of passive dosimeters, internal and external charged particle telescopes, and a tissue equivalent proportional counter (TEPC). Sixteen passive dosimeters, each consisting of TLD-100, TLD-300, TLD-600, and TLD-700 chips in a small acrylic holder, are placed throughout the habitable volume of the ISS. The TEPC and internal charged particle telescopes are portable and can be relocated to multiple locations in the Lab Module or Service Module. The external charged particle telescopes are mounted to a fixed boom attached to the starboard truss. Passive dosimeters were used in eleven monitoring periods over the period 20 May 1999 to 04 May 2003. Over this period exposure rates from TLD-100 measurements ranged from 0.120-0.300 mGy/d. Exposure rates inside the habitable volume are non-uniform: exposures vary by a factor of ˜ 1.7 from minimum to maximum, with the greatest non-uniformity occurring in the Lab Module. Highest daily exposure rates are near the window in the Lab Module, inside the Joint Airlock, and the sleep stations inside the Service Module, while the lowest rates occur inside the polyethylene-lined Temporary Sleep Station in the Lab Module, adjacent to the port ``arm'' of Node 1, and the aft end of the Service Module. The minimum exposure rates as measured by the passive dosimeters occurred in the spring of 2002, very close to the solar F10.7 emission maximum (Feb 2002), and two years after the sunspot maximum (Apr 2000). Exposure rates have since gradually increased as the sun's activity transitions towards solar minimum conditions. Since 01 Jun 2002, dose rates measured by the IV-CPDS, estimated from the count rate in first detector of the telescope's stack, ranged from ˜ 0.170-0.390 mGy/d. The maximum measured dose rate occurred 28 Oct 2003 during the ``Halloween'' space weather event. Interestingly, the minimum dose rate occurred 31 Oct 2003, near the end of the same remarkable space weather event, when the Earth was experiencing a significant Forbush decrease. The average IV-CPDS-measured dose rate increased from 0.194 to 0.234 mGy/d since 01 Jun 2002--an increase of ˜ 21% and a further indication that the low-Earth radiation environment is transitioning from solar maximum conditions towards solar minimum.

Bioavailability of cyanidin glycosides from natural chokeberry (Aronia melanocarpa) juice with dietary-relevant dose of anthocyanins in humans.

PubMed

Wiczkowski, Wieslaw; Romaszko, Ewa; Piskula, Mariusz K

2010-12-08

The aim of this study was to investigate the bioavailability of anthocyanins from chokeberry juice with a dietary-relevant dose of anthocyanins. Thirteen healthy volunteers consumed chokeberry juice providing 0.8 mg of anthocyanins/kg of body weight. Before and after juice consumption, blood and urine were collected. Concentration of anthocyanins was measured with HPLC-PDA-MS-ESI. Cyanidin-3-galactoside comprised 66% of total chokeberry anthocyanins. Eight cyanidin derivatives were found in blood and urine after juice consumption. The maximum plasma anthocyanin concentration of 32.7 ± 2.9 nmol/L was reached at 1.3 ± 0.1 h after juice consumption. The anthocyanins' urine excretion rate (62.9 ± 5.0 nmol/h) was the highest within the first 2 h. In total, 0.25 ± 0.02% of the ingested anthocyanins was excreted by the renal route during 24 h, mainly as metabolites of cyanidin. According to these observations, after consumption of a dietary-relevant dose of anthocyanins as natural chokeberry juice, anthocyanins and their metabolites were present in plasma and urine of volunteers.

Evaluating the consistency of location of the most severe acute skin reaction and highest skin dose measured by thermoluminescent dosimeter during radiotherapy for breast cancer

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

Sun, Li-Min, E-mail: limin.sun@yahoo.com; Huang, Chih-Jen; Department of Faculty of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skinmore » dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the contrary, TLD measurement of skin dose is less likely consistent with clinical observation when the most severe skin reaction occurred at the inframammary fold, breast, and areola/nipple areas (all the p > 0.05). Considering the common site of severe skin reaction over the axillary area, TLD measurement may be an appropriate way to predict skin reaction during RT.« less

A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans.

PubMed

Jensen, Kevin P; DeVito, Elise E; Herman, Aryeh I; Valentine, Gerald W; Gelernter, Joel; Sofuoglu, Mehmet

2015-11-01

Genome-wide association studies have implicated the CHRNA5-CHRNA3-CHRNB4 gene cluster in risk for heavy smoking and several smoking-related disorders. The heavy smoking risk allele might reduce the aversive effects of nicotine, but this hypothesis has not been tested in humans. We evaluated the effects of a candidate causal variant in CHRNA5, rs16969968, on the acute response to nicotine in European American (EA) and African American (AA) smokers (n=192; 50% AA; 73% male). Following overnight abstinence from nicotine, participants completed a protocol that included an intravenous (IV) dose of saline and two escalating IV doses of nicotine. The outcomes evaluated were the aversive, pleasurable, and stimulatory ratings of nicotine's effects, cardiovascular reactivity to nicotine, withdrawal severity, and cognitive performance before and after the nicotine administration session. The heavy smoking risk allele (rs16969968*A; frequency=28% (EA) and 6% (AA)) was associated with lower ratings of aversive effects (P<5 × 10(-8)) with marked specificity. This effect was evident in EA and AA subjects analyzed as separate groups and was most robust at the highest nicotine dose. Rs16969968*A was also associated with greater improvement on a measure of cognitive control (Stroop Task) following nicotine administration. These findings support differential aversive response to nicotine as one likely mechanism for the association of CHRNA5-CHRNA3-CHRNB4 with heavy smoking.

Tolerance to X-rays and Heavy Ions (Fe, He) in the Tardigrade Richtersius coronifer and the Bdelloid Rotifer Mniobia russeola.

PubMed

Jönsson, K Ingemar; Wojcik, Andrzej

2017-02-01

The aim of this study was to analyze tolerance to heavy ions in desiccated animals of the eutardigrade Richtersius coronifer and the bdelloid rotifer Mniobia russeola within the STARLIFE project. Both species were exposed to iron (Fe) and helium (He) ions at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in Chiba, Japan, and to X-rays at the German Aerospace Center (DLR) in Cologne, Germany. Results show no effect of Fe and He on viability up to 7 days post-rehydration in both R. coronifer and M. russeola, while X-rays tended to reduce viability in R. coronifer at the highest doses. Mean egg production rate tended to decline with higher doses in R. coronifer for all radiation types, but the pattern was not statistically confirmed. In M. russeola, there was no such tendency for a dose response in egg production rate. These results confirm the previously reported high tolerance to high linear energy transfer (LET) radiation in tardigrades and show for the first time that bdelloid rotifers are also very tolerant to high-LET radiation. These animal phyla represent the most desiccation- and radiation-tolerant animals on Earth and provide excellent eukaryotic models for astrobiological research. Key Words: Tardigrada-Rotifera-Radiation tolerance-Heavy ions-X-rays. Astrobiology 17, 163-167.

Costs and outcomes associated with IVF using recombinant FSH.

PubMed

Ledger, W; Wiebinga, C; Anderson, P; Irwin, D; Holman, A; Lloyd, A

2009-09-01

Cost and outcome estimates based on clinical trial data may not reflect usual clinical practice, yet they are often used to inform service provision and budget decisions. To expand understanding of assisted reproduction treatment in clinical practice, an economic evaluation of IVF/intracytoplasmic sperm injection (ICSI) data from a single assisted conception unit (ACU) in England was performed. A total of 1418 IVF/ICSI cycles undertaken there between October 2001 and January 2006 in 1001 women were analysed. The overall live birth rate was 22% (95% CI: 19.7-24.2), with the 30- to 34-year age group achieving the highest rate (28%). The average recombinant FSH (rFSH) dose/cycle prescribed was 1855 IU. Average cost of rFSH/cycle was 646 pound(SD: 219 pound), and average total cost/cycle was 2932 pound (SD: 422 pound). Economic data based on clinical trials informing current UK guidance assumes higher doses of rFSH dose/cycle (1750-2625 IU), higher average cost of drugs/cycle (1179 pound), and higher average total cost/cycle (3266 pound). While the outcomes in this study matched UK averages, total cost/cycle was lower than those cited in UK guidelines. Utilizing the protocols and (lower) rFSH dosages reported in this study may enable other ACU to provide a greater number of IVF/ICSI cycles to patients within given budgets.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

PubMed Central

Rühm, Werner; Azizova, Tamara; Bouffler, Simon; Cullings, Harry M; Grosche, Bernd; Little, Mark P; Shore, Roy S; Walsh, Linda; Woloschak, Gayle E

2018-01-01

Abstract In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan. PMID:29432579

Diverse spectrum of tumors in male Sprague-Dawley rats following single high doses of N-ethyl-N-nitrosourea (ENU).

PubMed Central

Stoica, G.; Koestner, A.

1984-01-01

In this study, 30-day-old male Sprague-Dawley rats, were inoculated intraperitoneally with a single dose of 45, 90, and 180 mg/kg of N-ethyl-N-Nitrosourea (ENU). A wide spectrum of neoplasms occurred. The most common tumors were those of the mammary gland and of the nervous system. Although the incidence of mammary tumors was highest in the two high-dose groups (90 and 180 mg/kg ENU), the incidence of neurogenic tumors was highest in the 45 mg/kg dose group. Mammary tumor development led to early death and precluded development of tumors of the nervous system, which require a longer latency period. A variety of neoplasms of other organs have been associated particularly with high doses of ENU, including ameloblastic tumors, carcinomas of the thyroid, prostate, kidney, pancreas, intestine, and lung, hemilymphatic tumors, and sarcomas. It is concluded that large doses of ENU are capable of expanding the tumor spectrum in young male rats beyond the target organs generally affected with lower doses, as described in earlier reports. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:6465287

The maximum single dose of resistant maltodextrin that does not cause diarrhea in humans.

PubMed

Kishimoto, Yuka; Kanahori, Sumiko; Sakano, Katsuhisa; Ebihara, Shukuko

2013-01-01

The objective of the present study was to determine the maximum dose of resistant maltodextrin (Fibersol)-2, a non-viscous water-soluble dietary fiber), that does not induce transitory diarrhea. Ten healthy adult subjects (5 men and 5 women) ingested Fibersol-2 at increasing dose levels of 0.7, 0.8, 0.9, 1.0, and 1.1 g/kg body weight (bw). Each administration was separated from the previous dose by an interval of 1 wk. The highest dose level that did not cause diarrhea in any subject was regarded as the maximum non-effective level for a single dose. The results showed that no subject of either sex experienced diarrhea at dose levels of 0.7, 0.8, 0.9, or 1.0 g/kg bw. At the highest dose level of 1.1 g/kg bw, no female subject experienced diarrhea, whereas 1 male subject developed diarrhea with muddy stools 2 h after ingestion of the test substance. Consequently, the maximum non-effective level for a single dose of the resistant maltodextrin Fibersol-2 is 1.0 g/kg bw for men and >1.1 g/kg bw for women. Gastrointestinal symptoms were gurgling sounds in 4 subjects (7 events) and flatus in 5 subjects (9 events), although no association with dose level was observed. These symptoms were mild and transient and resolved without treatment.

Simulation of computed tomography dose based on voxel phantom

NASA Astrophysics Data System (ADS)

Liu, Chunyu; Lv, Xiangbo; Li, Zhaojun

2017-01-01

Computed Tomography (CT) is one of the preferred and the most valuable imaging tool used in diagnostic radiology, which provides a high-quality cross-sectional image of the body. It still causes higher doses of radiation to patients comparing to the other radiological procedures. The Monte-Carlo method is appropriate for estimation of the radiation dose during the CT examinations. The simulation of the Computed Tomography Dose Index (CTDI) phantom was developed in this paper. Under a similar conditions used in physical measurements, dose profiles were calculated and compared against the measured values that were reported. The results demonstrate a good agreement between the calculated and the measured doses. From different CT exam simulations using the voxel phantom, the highest absorbed dose was recorded for the lung, the brain, the bone surface. A comparison between the different scan type shows that the effective dose for a chest scan is the highest one, whereas the effective dose values during abdomen and pelvis scan are very close, respectively. The lowest effective dose resulted from the head scan. Although, the dose in CT is related to various parameters, such as the tube current, exposure time, beam energy, slice thickness and patient size, this study demonstrates that the MC simulation is a useful tool to accurately estimate the dose delivered to any specific organs for patients undergoing the CT exams and can be also a valuable technique for the design and the optimization of the CT x-ray source.

Monte Carlo and Phantom Study of the Radiation Dose to the Body from Dedicated Computed Tomography of the Breast

PubMed Central

Sechopoulos, Ioannis; Vedantham, Srinivasan; Suryanarayanan, Sankararaman; D’Orsi, Carl J.; Karellas, Andrew

2008-01-01

Purpose To prospectively determine the radiation dose absorbed by the organs and tissues of the body during a dedicated computed tomography of the breast (DBCT) study using Monte Carlo methods and a phantom. Materials and Methods Using the Geant4 Monte Carlo toolkit, the Cristy anthropomorphic phantom and the geometry of a prototype DBCT was simulated. The simulation was used to track x-rays emitted from the source until their complete absorption or exit from the simulation limits. The interactions of the x-rays with the 65 different volumes representing organs, bones and other tissues of the anthropomorphic phantom that resulted in energy deposition were recorded. These data were used to compute the radiation dose to the organs and tissues during a complete DBCT acquisition relative to the average glandular dose to the imaged breast (ROD, relative organ dose), using the x-ray spectra proposed for DBCT imaging. The effectiveness of a lead shield for reducing the dose to the organs was investigated. Results The maximum ROD among the organs was for the ipsilateral lung with a maximum of 3.25%, followed by the heart and the thymus. Of the skeletal tissues, the sternum received the highest dose with a maximum ROD to the bone marrow of 2.24%, and to the bone surface of 7.74%. The maximum ROD to the uterus, representative of that of an early-stage fetus, was 0.026%. These maxima occurred for the highest energy x-ray spectrum (80 kVp) analyzed. A lead shield does not protect substantially the organs that receive the highest dose from DBCT. Discussion Although the dose to the organs from DBCT is substantially higher than that from planar mammography, they are comparable or considerably lower than those reached by other radiographic procedures and much lower than other CT examinations. PMID:18292479

Bioavailability of modified-release methylphenidate: influence of high-fat breakfast when administered intact and when capsule content sprinkled on applesauce.

PubMed

Lee, Lucy; Kepple, Joanne; Wang, Yibin; Freestone, Stephen; Bakhtiar, Ray; Wang, Yanfeng; Hossain, Mohammad

2003-09-01

Ritalin, an immediate release form of racemic methylphenidate hydrochloride, has been available in the USA since 1955 and is used for the treatment of ADHD. The objective of this study was to evaluate the pharmacokinetics of modified-release methylphenidate (highest single dose), Ritalin LA, when administered under fasting condition, with a high-fat breakfast, and when sprinkled on applesauce in healthy adult subjects. Blood samples were drawn for 24 h following a 40 mg oral administration. Most subjects appeared to produce a bimodal methylphenidate plasma concentration profile. In all three treatment groups, methylphenidate was rapidly absorbed with an initial average t(max(0-4)) of 1.3-2.4 h and an average peak plasma concentration [C(max(abs))] of 14.4-15.2 ng/ml. On average, both the rate [C(max(abs)) and t(max(abs))] and the extent of absorption (AUC(0- infinity)) of methylphenidate were similar when the capsule was given with a high fat breakfast and when the capsule contents were sprinkled onto applesauce, compared with the fasting state. No dose dumping was observed when the capsule was given with a high fat breakfast or when sprinkled onto applesauce. The dose was safe and generally well tolerated. Coadministration of a single oral dose of 40 mg methylphenidate capsule whether administered intact with a high-fat breakfast or sprinkled on applesauce did not affect the overall rate or extent of absorption of methylphenidate compared with the fasted condition. Copyright 2003 John Wiley & Sons, Ltd.

Naloxone and rimonabant reduce the reinforcing properties of exercise in rats.

PubMed

Rasmussen, Erin B; Hillman, Conrad

2011-12-01

Naloxone and rimonabant block neurotransmitter action of some drugs of abuse (such as ethanol, opiates, and nicotine), and thereby reduce drug seeking and self-administration by suppressing the drugs' reinforcing properties. The present study represents an attempt to elucidate whether these drugs may also reduce rewarding properties of other events, in this case, activity-based reinforcement. In Experiment 1, 10 obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min intervals. After baseline breakpoints were established, doses of naloxone (0.3-10 mg/kg) were administered prior to experimental sessions. Obese rats exhibited lower baseline breakpoints for wheel activity, lower response rates, and fewer revolutions compared to lean rats. Naloxone decreased revolutions and response rates for lean and obese rats, but did not reduce breakpoints. In Experiment 2, five Long-Evans rats pressed a door to unlock a wheel for 20 s of wheel activity. Doses of rimonabant (1-10 mg/kg) were administered before some experimental sessions. The highest dose of rimonabant suppressed breakpoints and response rates, but did not affect revolutions. These data suggest that both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse. The data also support the role of endocannabinoids in the reinforcing properties of exercise, an implication that is important in terms of CB1 antagonists as a type of pharmacotherapy.

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

PubMed

Duffy, T A; Iwanowicz, L R; McCormick, S D

2014-07-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights reserved.

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

PubMed

Kocher, David C; Apostoaei, A Iulian; Hoffman, F Owen; Trabalka, John R

2018-06-01

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.

PubMed

Sands, B E; Bank, S; Sninsky, C A; Robinson, M; Katz, S; Singleton, J W; Miner, P B; Safdi, M A; Galandiuk, S; Hanauer, S B; Varilek, G W; Buchman, A L; Rodgers, V D; Salzberg, B; Cai, B; Loewy, J; DeBruin, M F; Rogge, H; Shapiro, M; Schwertschlag, U S

1999-07-01

Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL-11 at doses of 5, 16, or 40 microgram. kg-1. wk-1 given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit. Subcutaneous injection of rhIL-11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhIL-11 40 microgram. kg-1. wk-1 as 2 or 5 weekly doses and 16 microgram. kg-1. week-1 as 5 weekly doses compared with patients receiving placebo (P < 0.05). Patients receiving 16 microgram. kg-1. wk-1 had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 microgram. kg-1. wk-1 given in 2 equal doses.

Potential third-party radiation exposure from outpatients treated with {sup 131}I for hyperthyroidism

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

Matheoud, Roberta; Reschini, Eugenio; Canzi, Cristina

2004-12-01

Thirty-three hyperthyroid patients treated with radioiodine (mean administered activity 414 MBq, range 163-555) were studied to determine if pretreatment dosimetry could be used to give radiation protection advice that could assure compliance with the effective dose constraints suggested by the European Commission. Effective doses to travelers, co-workers, and sleeping partners were estimated by integrating the effective dose rate-versus-time curve obtained by fitting the dose rates measured several times after radioiodine administration to a biexponential function. The mean estimated effective doses to travelers, co-workers, and sleeping partners were 0.11 mSv (0.05-0.24), 0.24 mSv (0.07-0.52), and 1.8 mSv (0.6-4.1), respectively. The bestmore » correlation was found between effective dose (D) in mSv and maximum activity (AU{sub max}) in MBq taken up in the thyroid: D{sub traveler}=0.0005*(AU{sub max})+0.04 (r=0.88,p<0.01); D{sub co-worker}=0.0013*(AU{sub max})+0.03(r=0.89,p<0.01); D{sub sleepingpartners}=0.0105*(AU{sub max})+0.16 (r=0.93,p<0.01). Private/public transports are always allowed. For the co-workers the effective dose constraint of 0.3 mSv is met without restrictions and with 3 days off work if AU{sub max} is lower or higher than 185 MBq, respectively. For the sleeping partners the effective dose constraint of 3 mSv is met without restriction and with 4 nights separate sleeping arrangements if AU{sub max} is lower or higher than 185 MBq, respectively. The potential for contamination by the patients was determined from perspiration samples taken from the patient's hands, forehead, and neck and in saliva at 4, 24, and 48 h after radioiodine treatment. The mean highest {sup 131}I activity levels for hands, forehead, neck, and saliva were 4.1 Bq/cm{sup 2}, 1.9 Bq/cm{sup 2}, 0.9 Bq/cm{sup 2}, and 796 kBq/g, respectively. The results indicate that there is minimal risk of contamination from these patients.« less

Influence of Herbicide Triasulfuron on Soil Microbial Community in an Unamended Soil and a Soil Amended with Organic Residues

PubMed Central

Pose-Juan, Eva; Igual, José M.; Sánchez-Martín, María J.; Rodríguez-Cruz, M. S.

2017-01-01

The effect of organic amendments and pesticides on a soil microbial community has garnered considerable interest due to the involvement of microorganisms in numerous soil conservation and maintenance reactions. The aim of this work was to assess the influence on a soil microbial community of the simultaneous application of the herbicide triasulfuron at three doses (2, 10, and 50 mg kg-1), with an organic amendment [sewage sludge (SS) or green compost (GC)]. Dissipation kinetics, soil microbial biomass, dehydrogenase activity (DHA) and respiration, and the profile of phospholipid fatty acids (PLFAs) extracted from the soil, were determined in unamended (S) soil and amended (S+SS and S+GC) ones. Triasulfuron dissipation followed the single first-order kinetics model. Half-life (DT50) values were higher in the amended soils than in the unamended one for the 10 and 50 mg kg-1 doses. The dissipation rates were lower in the S+GC soil for the three herbicide doses applied. In general, soil biomass, DHA and respiration values increased in SS- and GC-amended soils compared to the unamended one. DHA values decreased (S and S+SS) or increased (S+GC) with the incubation time of soil with herbicide at the different doses applied. Respiration values increased with the herbicide doses applied and decreased with the incubation time, although maximum values were obtained for soils treated with the highest dose after 70 days of incubation. PLFA analysis indicated different effects of triasulfuron on the soil microbial community structure depending on the organic amendments. While the increasing triasulfuron doses resulted in deeper alterations in the S soil, the time after triasulfuron application was the most important variation in the S+SS and S+GC soils. The overall results indicate that the soil amendment has an effect on herbicide dissipation rate and the soil microbial community. Initially, a high dose of triasulfuron had detrimental effects on the soil microbial community, which is important in the case of the long-term use of this compound. PMID:28337188

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

miR-26b enhances radiosensitivity of hepatocellular carcinoma cells by targeting EphA2.

PubMed

Jin, Qiao; Li, Xiang Jun; Cao, Pei Guo

2016-08-01

Although low-dose radiotherapy (RT) that involves low collateral damage is more suitable for hepatocellular carcinoma (HCC) than traditional high-dose RT, but to achieve satisfactory therapeutic effect with low-dose RT, it is necessary to sensitize HCC cells to irradiation. This study was aimed to determine whether radiosensitivity of HCC cells can be enhanced using miR-26b by targeting erythropoietin producing human hepatocelluar A2 (EphA2). The levels of miR-26b and EphA2 expression in multiple HCC cell lines were assessed by qPCR and western blotting, respectively, and compared with those in a hepatic cell line. HCC 97H cells were transfected with miR-26b mimics, EphA2-ShRNA or EphA2 over-expression vector before exposure to low-dose irradiation. Different degrees of miR-26b down-regulation and EphA2 up-regulation were observed in all HCC cell lines, among which the HCC 97H cell line expressed the lowest level of miR-26b and highest level of EphA2. EphA2 was verified as the target of miR-26b by dual luciferase reporter assay. HCC 97H cells transfected with miR-26b mimics or EphA2-ShRNA reduced the expression of EphA2 protein, with significantly lower cell proliferation rate and cell invasion ability and higher apoptosis rate in response to low-dose irradiation than those in the non-transfected cells. These results were reversed after EphA2 was overexpressed by transfection with the EphA2 overexpression vector. Co-transfection with miR-26b mimics and EphA2 overexpression vector barely altered EphA2 expression level and cell response to low-dose irradiation. These data suggest that miR-26b enhances radiosensitivity of HCC 97H cells by targeting EphA2 protein.

Results on Dose Distributions in a Human Body from the Matroshka-R Experiment onboard the ISS Obtained with the Tissue-Equivalent Spherical Phantom

NASA Astrophysics Data System (ADS)

Shurshakov, Vyacheslav; Nikolaev, Igor; Kartsev, Ivan; Tolochek, Raisa; Lyagushin, Vladimir

The tissue-equivalent spherical phantom (32 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been used on board the ISS in Matroshka-R experiment for more than 10 years. Both passive and active space radiation detectors can be located inside the phantom and on its surface. Due to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a human body. Originally the spherical phantom was installed in the star board crew cabin of the ISS Service Module, then in the Piers-1, MIM-2, and MIM-1 modules of the ISS Russian segment, and finally in JAXA Kibo module. Total duration of the detector exposure is more than 2000 days in 9 sessions of the space experiment. In the first phase of the experiment with the spherical phantom the dose measurements were realized with only passive detectors (thermoluminescent and solid state track detectors). The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. After each session the passive detectors are returned to the ground. The results obtained show the dose difference on the phantom surface as much as a factor of 2, the highest dose being usually observed close to the outer wall of the compartment, and the lowest dose being in the opposite location along the phantom diameter. However, because of the ISS module shielding properties an inverse dose distribution in a human body can be observed when the dose rate maximum is closer to the geometrical center of the module. Maximum dose rate measured in the phantom is obviously due to the action of two radiation sources, namely, galactic cosmic rays (GCR) and Earth’ radiation belts. Minimum dose rate is produced mainly by the strongly penetrating GCR particles and is mostly observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the ISS compartments are also estimated with the spherical phantom data. The estimated effective dose rate is found to be from 10 % to 15 % lower than the averaged dose on the phantom surface as dependent on the attitude of the critical organs. If compared with the anthropomorphic phantom Rando used inside and outside the ISS earlier, the Matroshka-R space experiment spherical phantom has lower mass, smaller size, and requires less crew time for the detector installation/retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. New sessions with the two tissue-equivalent phantoms are of great interest. Development of modified passive and active detector sets is in progress for the future ISS expeditions. Both the spherical and Rando-type phantoms proved their effectiveness to measure the critical organ doses and effective doses in-flight and if supplied with modernized dosimeters can be recommended for future exploratory manned missions to monitor continuously the crew exposure to space radiation.

Commuters' exposure to particulate matter air pollution is affected by mode of transport, fuel type, and route.

PubMed

Zuurbier, Moniek; Hoek, Gerard; Oldenwening, Marieke; Lenters, Virissa; Meliefste, Kees; van den Hazel, Peter; Brunekreef, Bert

2010-06-01

Commuters are exposed to high concentrations of air pollutants, but little quantitative information is currently available on differences in exposure between different modes of transport, routes, and fuel types. The aim of our study was to assess differences in commuters' exposure to traffic-related air pollution related to transport mode, route, and fuel type. We measured particle number counts (PNCs) and concentrations of PM2.5 (particulate matter

Environmental hazards and distribution of radioactive black sand along the Rosetta coastal zone in Egypt using airborne spectrometric and remote sensing data.

PubMed

Kaiser, M F; Aziz, A M; Ghieth, B M

2014-11-01

High-resolution airborne gamma ray spectrometry, conducted in 2003, was used to estimate radioactive elements spatial abundance along the Rosetta coastal zone area. It was noticed that both Uranium and Thorium are concentrated in the black sand deposits along the beach. In contrary, Potassium was observed in high level abundance at the cultivated Nile Delta lands due to the accumulated usage of fertilizers. Exposure Rate (ER), Absorbed Dose Rate (ADR) and Annual Effective Dose Rate (AEDR) were calculated to evaluate the radiation background influence in human. Results indicated that the human body in the study sites is subjected to radiation hazards exceeds the accepted limit for long duration exposure. In addition, the areas covered by the highest concentration of Uranium and Thorium show the highest level of radiogenic heat production. Detection the environmental hazards of the radioactive black sands in the study site encouraged this research to monitor the spatial and temporal distribution of these sediments. The Landsat Thematic Mapper images acquired in 1990, 2003 and 2013 were analyzed using remote sensing image processing techniques. Image enhancements, classification and changes detection indicated a positive significant relationship between the patterns of coastline changes and distribution of the radioactive black sand in the study sites. The radioactive black sands are usually concentrated in the eroded areas. Therefore, in 1990 high concentration of the radioactive black sands were observed along the eastern and western flanks of the Rosetta promontory. Distribution of these sediments decreased due to the construction of the protective sea walls. Most of the radioactive black sands are transported toward the east in Abu Khashaba bay under the effect of the longshore currents and toward the west in Alexandria and Abu Quir bay under the action of the seasonal reverse currents. Copyright © 2014 Elsevier Ltd. All rights reserved.

WE-H-BRC-09: Simulated Errors in Mock Radiotherapy Plans to Quantify the Effectiveness of the Physics Plan Review

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

Gopan, O; Kalet, A; Smith, W

2016-06-15

Purpose: A standard tool for ensuring the quality of radiation therapy treatments is the initial physics plan review. However, little is known about its performance in practice. The goal of this study is to measure the effectiveness of physics plan review by introducing simulated errors into “mock” treatment plans and measuring the performance of plan review by physicists. Methods: We generated six mock treatment plans containing multiple errors. These errors were based on incident learning system data both within the department and internationally (SAFRON). These errors were scored for severity and frequency. Those with the highest scores were included inmore » the simulations (13 errors total). Observer bias was minimized using a multiple co-correlated distractor approach. Eight physicists reviewed these plans for errors, with each physicist reviewing, on average, 3/6 plans. The confidence interval for the proportion of errors detected was computed using the Wilson score interval. Results: Simulated errors were detected in 65% of reviews [51–75%] (95% confidence interval [CI] in brackets). The following error scenarios had the highest detection rates: incorrect isocenter in DRRs/CBCT (91% [73–98%]) and a planned dose different from the prescribed dose (100% [61–100%]). Errors with low detection rates involved incorrect field parameters in record and verify system (38%, [18–61%]) and incorrect isocenter localization in planning system (29% [8–64%]). Though pre-treatment QA failure was reliably identified (100%), less than 20% of participants reported the error that caused the failure. Conclusion: This is one of the first quantitative studies of error detection. Although physics plan review is a key safety measure and can identify some errors with high fidelity, others errors are more challenging to detect. This data will guide future work on standardization and automation. Creating new checks or improving existing ones (i.e., via automation) will help in detecting those errors with low detection rates.« less

Influence of monte carlo variance with fluence smoothing in VMAT treatment planning with Monaco TPS.

PubMed

Sarkar, B; Manikandan, A; Nandy, M; Munshi, A; Sayan, P; Sujatha, N

2016-01-01

The study aimed to investigate the interplay between Monte Carlo Variance (MCV) and fluence smoothing factor (FSF) in volumetric modulated arc therapy treatment planning by using a sample set of complex treatment planning cases and a X-ray Voxel Monte Carlo-based treatment planning system equipped with tools to tune fluence smoothness as well as MCV. The dosimetric (dose to tumor volume, and organ at risk) and physical characteristic (treatment time, number of segments, and so on) of a set 45 treatment plans for all combinations of 1%, 3%, 5% MCV and 1, 3, 5 FSF were evaluated for five carcinoma esophagus cases under the study. Increase in FSF reduce the treatment time. Variation of MCV and FSF gives a highest planning target volume (PTV), heart and lung dose variation of 3.6%, 12.8% and 4.3%, respectively. The heart dose variation was highest among all organs at risk. Highest variation of spinal cord dose was 0.6 Gy. Variation of MCV and FSF influences the organ at risk (OAR) doses significantly but not PTV coverage and dose homogeneity. Variation in FSF causes difference in dosimetric and physical parameters for the treatment plans but variation of MCV does not. MCV 3% or less do not improve the plan quality significantly (physical and clinical) compared with MCV greater than 3%. The use of MCV between 3% and 5% gives similar results as 1% with lesser calculation time. Minimally detected differences in plan quality suggest that the optimum FSF can be set between 3 and 5.

[Comparison of antibody persistence between live attenuated and inactivated hepatitis A vaccines].

PubMed

Liu, Huai-Feng; Zhang, Xin-Jiang; Zhang, Jian-Li

2009-08-01

To study the antibody persistence of live attenuated hepatitits A vaccine, and to compare the antibody between with inactivated vaccine. 211 HAV susceptible children were divided randomly into three groups, Group A was injected three doses HepA-L at 0, 6 and 12 monthes; Group B was administrated two dose HepA-L at 0 and 6 months, and group C was immunized with inactivated vaccine at month 0 and 6. Serum samples were detected for Anti-HAV at 1, 6, 7, 12, 13, 24, 84 months after vaccination in each group. The seroconversion rates reached 100% after 2nd dose in all groups. The highest GMC was 2938.1 mlU/ml, founded in group C, and it was 1315.6 mlU/ml and 1586 mlU/ml in group A and B respectively. After the 3rd dose at month 12 in group A, the antibody increased dramatic, which reached 1945.3 mlU/ml. 84 months after first dose in each group, the antibody can be detected from all subjects. Though the GMC in group A declined to 336.8 mlU/ml, it was significant higher than that in group B and C. The good booster effect with HepA-L was well observed in a short-term. The immune response induced by 2 to 3 doses HepA-L could compete with inactivated hepatitis A vaccine. However, long-term effects of both vaccines need further study.

Vorapaxar and optimal aspirin dose: The FDA outlook.

PubMed

Serebruany, Victor L; Fortmann, Seth D; Kim, Moo Hyun

2016-01-15

Vorapaxar, a novel thrombin PAR-1 inhibitor, approved for post-myocardial infarction, and peripheral artery disease indications has been tested in 2 major clinical trials. In the successful TRA2P, antecedent aspirin (ASA) has been used in 94% of patients, and in failed TRACER in over 96% of patients. However, both trial publications were silent on the impact of ASA dose on clinical outcomes after voraparax. We determined which ASA dose range should be used in combination with voraparax based on the TRA2P and TRACER secondary FDA review. The data suggest that for both voraparax trials, younger patients, males, and diabetics received higher ASA doses. The interactions between voraparax efficacy and ASA dose ≥ 300 mg was marginally significant by Cox regressions for TRA2P (CI=1.00-1.61; p=0.048) and strongly trended in TRACER (CI=0.98-1.47; p=0.073). Bleeding rates were overall slightly higher with voraparax than with placebo, and were the highest in patients receiving ASA dosages ≥ 300 mg. However, there were no interactions between ASA dose and GUSTO moderate/severe bleeding. In conclusion, the efficacy of voraparax in TRA2P and TRACER, was slightly worse while bleeding was substantially worse with the higher over 300 mg/day of ASA dosages. Voraparax label should recommend ASA daily use in 75 to 100mg range for concomitant use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in Japanese patients with castration-resistant prostate cancer.

PubMed

Mukai, Hirofumi; Takahashi, Shunji; Nozawa, Masahiro; Onozawa, Yusuke; Miyazaki, Jun; Ohno, Keiji; Suzuki, Kazuhiro

2014-04-01

The purpose of the study is to analyze the pharmacokinetic (PK) profile of cabazitaxel and evaluate its safety and tolerability as a 1-h IV infusion every 3 weeks in Japanese patients with castration-resistant prostate cancer (CRPC). Seventeen patients were treated with cabazitaxel at doses of 20 and 25 mg/m(2) for PK analyses. Dose escalation was performed only in the absence of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was the highest dose at which less than 33 % of the patients developed DLT. Cabazitaxel exhibited a triphasic elimination profile with a long terminal half-life of 116 ± 29.0 or 113 ± 28.0 h after IV infusion of 20 or 25 mg/m(2) cabazitaxel, respectively. The major differences in the PK parameters of cabazitaxel and docetaxel were cabazitaxel's fairly high clearance rate, representing approximately half the hepatic flow, and its large volume of distribution at steady-state conditions. No DLT was observed during Cycle 1. Mild-to-moderate hematological adverse events (AEs), including neutropenia, and other AEs typically associated with taxanes were observed; all AEs were manageable. Cabazitaxel at 25 mg/m(2) every 3 weeks was selected as the MTD in Japanese patients. The PK parameters of cabazitaxel in Japanese CRPC patients were comparable with those previously determined in Caucasian subjects. The safety and tolerability of cabazitaxel were also comparable in both ethnic populations.

Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy

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

Tward, Jonathan D., E-mail: Jonathan.Tward@hci.utah.edu; Jarosek, Stephanie; Chu, Haitao

Purpose: Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Methods and Materials: Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results–Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, andmore » the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Results: Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Conclusions: Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus EBRT) increases the risk of severe UAEs compared with HDR alone or LDR alone. The highest increased risk of urinary toxicity occurs within the 2 years after therapy and then declines to an approximately 1% increase in incidence per year.« less

Time Course and Accumulated Risk of Severe Urinary Adverse Events After High- Versus Low-Dose-Rate Prostate Brachytherapy With or Without External Beam Radiation Therapy.

PubMed

Tward, Jonathan D; Jarosek, Stephanie; Chu, Haitao; Thorpe, Cameron; Shrieve, Dennis C; Elliott, Sean

2016-08-01

Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence, and radiation cystitis. We compared the incidence of grade 3 UAEs, according to the Common Terminology Criteria for Adverse Events, after low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy, as well as after LDR plus external beam radiation therapy (EBRT) and HDR plus EBRT. Men aged >65 years with nonmetastatic prostate cancer were identified from the Surveillance, Epidemiology, and End Results-Medicare database who were treated with LDR (n=12,801), HDR (n=685), LDR plus EBRT (n=8518), or HDR plus EBRT (n=2392). The populations were balanced by propensity weighting, and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared with those in a cohort of men not treated for prostate cancer. Median follow-up was 4.3 years. At 8 years, the propensity-weighted cumulative UAE incidence was highest after HDR plus EBRT (26.6% [95% confidence interval, 23.8%-29.7%]) and lowest after LDR (15.7% [95% confidence interval, 14.8%-16.6%]). The absolute excess risk over nontreated controls at 8 years was 1.9%, 3.8%, 8.4%, and 12.9% for LDR, HDR, LDR plus EBRT, and HDR plus EBRT, respectively. These represent numbers needed to harm of 53, 26, 12, and 8 persons, respectively. The additional risk of development of a UAE related to treatment for LDR, LDR plus EBRT, and HDR plus EBRT was greatest within the 2 years after treatment and then continued to decline over time. Beyond 4 years, the risk of development of a new severe UAE matched the baseline risk of the control population for all treatments. Toxicity differences were observed between LDR and HDR, but the differences did not meet statistical significance. However, combination radiation therapy (either HDR plus EBRT or LDR plus EBRT) increases the risk of severe UAEs compared with HDR alone or LDR alone. The highest increased risk of urinary toxicity occurs within the 2 years after therapy and then declines to an approximately 1% increase in incidence per year. Copyright © 2016. Published by Elsevier Inc.

Testosterone inhibits the growth of prostate cancer xenografts in nude mice.

PubMed

Song, Weitao; Soni, Vikram; Soni, Samit; Khera, Mohit

2017-09-07

Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice. Different serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested. The data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001). These results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.

Quantitative assessment of the cataractogenic potential of very low doses of neutrons

NASA Technical Reports Server (NTRS)

Worgul, B. V.; Medvedovsky, C.; Huang, Y.; Marino, S. A.; Randers-Pehrson, G.; Brenner, D. J.

1996-01-01

We report on the prevalence and relative biological effectiveness (RBE) for various stages of lens opacification in rats induced by very low doses (2 to 250 mGy) of medium-energy (440 keV) neutrons, compared to those for X rays. Neutron doses were delivered either in a single fraction or in four separate fractions and the irradiated animals were followed for over 100 weeks. At the highest observed dose (250 mGy) and at early observation times, there was evidence of an inverse dose-rate effect; i.e., a fractionated exposure was more potent than a single exposure. Neutron RBEs relative to X rays were estimated using a non-parametric technique. The results were only weakly dependent on time postirradiation. At 30 weeks, for example, 80% confidence intervals for the RBE of acutely delivered neutrons relative to X rays were 8-16 at 250 mGy, 10-20 at 50 mGy, 50-100 at 10 mGy and 250-500 at 2 mGy. The results are consistent with the estimated neutron RBEs in Japanese A-bomb survivors, though broad confidence bounds are present in the Japanese results. Our findings are also consistent with data reported earlier for cataractogenesis induced by heavy ions in rats, mice, and rabbits. We conclude from these results that, at very low doses (<10 mGy), the RBE for neutron-induced cataractogenesis is considerably larger than the RBE of 20 commonly used, and use of a significantly larger value for calculating equivalent dose would be prudent.

Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men.

PubMed Central

Ohnishi, A; Orita, Y; Okahara, R; Fujihara, H; Inoue, T; Yamamura, Y; Yabuuchi, Y; Tanaka, T

1993-01-01

Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men. Images PMID:8254021

Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress.

PubMed

Kennedy, David O; Little, Wendy; Haskell, Crystal F; Scholey, Andrew B

2006-02-01

Melissa officinalis (lemon balm) and Valeriana officinalis (valerian) have been used both traditionally and contemporaneously as mild sedatives, anxiolytics and hypnotics. Recent research has suggested that both may attenuate laboratory induced stress. As the two herbs are most often sold in combination with each other the current study assessed the anxiolytic properties of such a combination during laboratory-induced stress. In this double-blind, placebo-controlled, randomized, balanced cross-over experiment, 24 healthy volunteers received three separate single doses (600 mg, 1200 mg, 1800 mg) of a standardized product containing M. officinalis and V. officinalis extracts, plus a placebo, on separate days separated by a 7 day wash out period. Modulation of mood and anxiety were assessed during pre-dose and 1 h, 3 h and 6 h post-dose completions of a 20 min version of the Defined Intensity Stressor Simulation (DISS) battery. Cognitive performance on the four concurrent tasks of the battery was also assessed. The results showed that the 600 mg dose of the combination ameliorated the negative effects of the DISS on ratings of anxiety. However, the highest dose (1800 mg) showed an increase in anxiety that was less marked but which reached significance during one testing session. In addition, all three doses led to decrements in performance on the Stroop task module within the battery, and the two lower doses led to decrements on the overall score generated on the DISS battery. These results suggest that a combination of Melissa officinalis and Valeriana officinalis possesses anxiolytic properties that deserve further investigation. Copyright 2006 John Wiley & Sons, Ltd.

Image-Based 3D Treatment Planning for Vaginal Cylinder Brachytherapy: Dosimetric Effects of Bladder Filling on Organs at Risk

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

Hung, Jennifer; Shen Sui; De Los Santos, Jennifer F.

2012-07-01

Purpose: To investigate the dosimetric effects of bladder filling on organs at risk (OARs) using three-dimensional image-based treatment planning for vaginal cylinder brachytherapy. Methods and Materials: Twelve patients with endometrial or cervical cancer underwent postoperative high-dose rate vaginal cylinder brachytherapy. For three-dimensional planning, patients were simulated by computed tomography with an indwelling catheter in place (empty bladder) and with 180 mL of sterile water instilled into the bladder (full bladder). The bladder, rectum, sigmoid, and small bowel (OARs) were contoured, and a prescription dose was generated for 10 to 35 Gy in 2 to 5 fractions at the surface ormore » at 5 mm depth. For each OAR, the volume dose was defined by use of two different criteria: the minimum dose value in a 2.0-cc volume receiving the highest dose (D{sub 2cc}) and the dose received by 50% of the OAR volume (D{sub 50%}). International Commission on Radiation Units and Measurements (ICRU) bladder and rectum point doses were calculated for comparison. The cylinder-to-bowel distance was measured using the shortest distance from the cylinder apex to the contoured sigmoid or small bowel. Statistical analyses were performed with paired t tests. Results: Mean bladder and rectum D{sub 2cc} values were lower than their respective ICRU doses. However, differences between D{sub 2cc} and ICRU doses were small. Empty vs. full bladder did not significantly affect the mean cylinder-to-bowel distance (0.72 vs. 0.92 cm, p = 0.08). In contrast, bladder distention had appreciable effects on bladder and small bowel volume dosimetry. With a full bladder, the mean small bowel D{sub 2cc} significantly decreased from 677 to 408 cGy (p = 0.004); the mean bladder D{sub 2cc} did not increase significantly (1,179 cGy vs. 1,246 cGy, p = 0.11). Bladder distention decreased the mean D{sub 50%} for both the bladder (441 vs. 279 cGy, p = 0.001) and the small bowel (168 vs. 132 cGy, p = 0.001). Rectum and sigmoid volume doses were not affected by bladder filling. Conclusions: In high-dose rate vaginal cylinder brachytherapy, treatment with a distended bladder preferentially reduces high dose to the small bowel around the vaginal cuff without a significant change in dose to the bladder, rectum, or sigmoid.« less

Dose-response relationship of autonomic nervous system responses to individualized training impulse in marathon runners.

PubMed

Manzi, Vincenzo; Castagna, Carlo; Padua, Elvira; Lombardo, Mauro; D'Ottavio, Stefano; Massaro, Michele; Volterrani, Maurizio; Iellamo, Ferdinando

2009-06-01

In athletes, exercise training induces autonomic nervous system (ANS) adaptations that could be used to monitor training status. However, the relationship between training and ANS in athletes has been investigated without regard for individual training loads. We tested the hypothesis that in long-distance athletes, changes in ANS parameters are dose-response related to individual volume/intensity training load and could predict athletic performance. A spectral analysis of heart rate (HR), systolic arterial pressure variability, and baroreflex sensitivity by the sequences technique was investigated in eight recreational athletes during a 6-mo training period culminating with a marathon. Individualized training load responses were monitored by a modified training impulse (TRIMP(i)) method, which was determined in each athlete using the individual HR and lactate profiling determined during a treadmill test. Monthly TRIMP(i) steadily increased during the training period. All the ANS parameters were significantly and very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.90 to 0.99; P < 0.001). Variance, high-frequency oscillations of HR variability (HRV), and baroreflex sensitivity resembled a bell-shaped curve with a minimum at the highest TRIMP(i), whereas low-frequency oscillations of HR and systolic arterial pressure variability and the low frequency (LF)-to-high frequency ratio resembled an U-shaped curve with a maximum at the highest TRIMP(i). The LF component of HRV assessed at the last recording session was significantly and inversely correlated to the time needed to complete the nearing marathon. These results suggest that in recreational athletes, ANS adaptations to exercise training are dose related on an individual basis, showing a progressive shift toward a sympathetic predominance, and that LF oscillations in HRV at peak training load could predict athletic achievement in this athlete population.

Lithospheric flexure revealed by Pleistocene emerged marine terraces on the southern Hawaiian Islands

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

Jones, A.T.

1992-01-01

New field and geochronological data from emerged marine deposits in the southern Hawaiian Islands suggest uplift of the islands of Molokai, Lanai and Oahu. Corals from these islands were dated by ESR. The accumulated dose for aragonitic coral at ESR signal, g = 2.0007, was determined by the additive dose method. The environmental dose rate was estimated from the Uranium concentration in corals and by using an estimate of 2.5 rad/a for the cosmic ray dose. The ESR ages of the highest terraces on Molokai are 290 [+-] 31 ka (30 m), on Lanai 217 [+-] 19 ka (50 m)more » and on Oahu 468 [+-] 36 ka (28 m). The age and elevation of the marine terraces are interpreted to imply uplift during the Late Quaternary. Lithospheric flexure combined with horizontal plate motion is proposed as a mechanism to describe the pattern of uplifted terraces on these islands. Using two-dimensional elastic plate models, the height of maximum bulge is approximately 4% to 7% of the maximum deflection for a continuous or broken plate model. Drowned reefs off Hawaii indicate subsidence of 1 km since 340 ka. Thus, the magnitude of observed uplift (30--50 m) is consistent with theoretical maximum bulge heights derived from numerical results.« less

A process evaluation of implementing a vocational enablement protocol for employees with hearing difficulties in clinical practice.

PubMed

Gussenhoven, Arjenne H M; Singh, Amika S; Goverts, S Theo; van Til, Marten; Anema, Johannes R; Kramer, Sophia E

2015-08-01

A multidisciplinary vocational rehabilitation programme, the Vocational Enablement Protocol (VEP) was developed to address the specific needs of employees with hearing difficulties. In the current study we evaluated the process of implementing the VEP in audiologic care among employees with hearing impairment. In conjunction with a randomized controlled trial, we collected and analysed data on seven process parameters: recruitment, reach, fidelity, dose delivered, dose received and implemented, satisfaction, and perceived benefit. Sixty-six employees with hearing impairment participated in the VEP. The multidisciplinary team providing the VEP comprised six professionals. The professionals performed the VEP according to the protocol. Of the recommendations delivered by the professionals, 31% were perceived as implemented by the employees. Compliance rate was highest for hearing-aid uptake (51%). Both employees and professionals were highly satisfied with the VEP. Participants rated good perceived benefit from it. Our results indicate that the VEP could be a useful treatment for employees with hearing difficulties from a process evaluation perspective. Implementation research in the audiological setting should be encouraged in order to further provide insight into parameters facilitating or hindering successful implementation of an intervention and to improve its quality and efficacy.

Calcium-alginate/carbon nanotubes/TiO2 composite beads for removal of bisphenol A.

PubMed

Hartono, Maria R; Kushmaro, Ariel; Marks, Robert S; Chen, Xiaodong

2016-10-01

In this study, composite calcium-alginate/carbon nanotubes/TiO 2 beads were prepared and tested for their potential in the removal of bisphenol A (BPA) from aqueous solutions. The removal traits were inspected using a fixed-bed sorption column. By varying parameters such as bed height (15-20 cm), flow rate (2.0-6.0 mL.min -1 ) and inlet BPA concentration (10-30 mg.L -1 ) we assessed the removal capacity of these composites. The highest sorption capacity of 5.46 mg.g -1 was achieved at 10 mg.L -1 BPA concentration, 2.0 mL.min -1 flow rate and 20 cm bed height at saturation. Adams-Bohart, Yoon-Nelson and Dose-Response isotherm models were applied to evaluate the performance of the column at different inlet concentrations. The experimental data satisfactorily fit the Dose-Response model with high correlation (r 2 > 0.97) across the breakthrough curve. Regeneration of the used adsorbent beads were performed by immersion in the desorption solvent followed by light irradiation. It was postulated that inclusion of TiO 2 facilitates the desorbed pollutant degradation from the used adsorbent beads.

Time profile of cosmic radiation exposure during the EXPOSE-E mission: the R3DE instrument.

PubMed

Dachev, Tsvetan; Horneck, Gerda; Häder, Donat-Peter; Schuster, Martin; Richter, Peter; Lebert, Michael; Demets, Rene

2012-05-01

The aim of this paper is to present the time profile of cosmic radiation exposure obtained by the Radiation Risk Radiometer-Dosimeter during the EXPOSE-E mission in the European Technology Exposure Facility on the International Space Station's Columbus module. Another aim is to make the obtained results available to other EXPOSE-E teams for use in their data analysis. Radiation Risk Radiometer-Dosimeter is a low-mass and small-dimension automatic device that measures solar radiation in four channels and cosmic ionizing radiation as well. The main results of the present study include the following: (1) three different radiation sources were detected and quantified-galactic cosmic rays (GCR), energetic protons from the South Atlantic Anomaly (SAA) region of the inner radiation belt, and energetic electrons from the outer radiation belt (ORB); (2) the highest daily averaged absorbed dose rate of 426 μGy d(-1) came from SAA protons; (3) GCR delivered a much smaller daily absorbed dose rate of 91.1 μGy d(-1), and the ORB source delivered only 8.6 μGy d(-1). The analysis of the UV and temperature data is a subject of another article (Schuster et al., 2012 ).

Out-of-field doses and neutron dose equivalents for electron beams from modern Varian and Elekta linear accelerators.

PubMed

Cardenas, Carlos E; Nitsch, Paige L; Kudchadker, Rajat J; Howell, Rebecca M; Kry, Stephen F

2016-07-08

Out-of-field doses from radiotherapy can cause harmful side effects or eventually lead to secondary cancers. Scattered doses outside the applicator field, neutron source strength values, and neutron dose equivalents have not been broadly investigated for high-energy electron beams. To better understand the extent of these exposures, we measured out-of-field dose characteristics of electron applicators for high-energy electron beams on two Varian 21iXs, a Varian TrueBeam, and an Elekta Versa HD operating at various energy levels. Out-of-field dose profiles and percent depth-dose curves were measured in a Wellhofer water phantom using a Farmer ion chamber. Neutron dose was assessed using a combination of moderator buckets and gold activation foils placed on the treatment couch at various locations in the patient plane on both the Varian 21iX and Elekta Versa HD linear accelerators. Our findings showed that out-of-field electron doses were highest for the highest electron energies. These doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. The Elekta linear accelerator had higher electron out-of-field doses than the Varian units examined, and the Elekta dose profiles exhibited a second dose peak about 20 to 30 cm from central-axis, which was found to be higher than typical out-of-field doses from photon beams. Electron doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. With respect to neutron dosimetry, Q values and neutron dose equivalents increased with electron beam energy. Neutron contamination from electron beams was found to be much lower than that from photon beams. Even though the neutron dose equivalent for electron beams represented a small portion of neutron doses observed under photon beams, neutron doses from electron beams may need to be considered for special cases.

Evaluating the consistency of location of the most severe acute skin reaction and highest skin dose measured by thermoluminescent dosimeter during radiotherapy for breast cancer.

PubMed

Sun, Li-Min; Huang, Chih-Jen; Chen, Hsiao-Yun; Chang, Gia-Hsin; Tsao, Min-Jen

2016-01-01

We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the contrary, TLD measurement of skin dose is less likely consistent with clinical observation when the most severe skin reaction occurred at the inframammary fold, breast, and areola/nipple areas (all the p > 0.05). Considering the common site of severe skin reaction over the axillary area, TLD measurement may be an appropriate way to predict skin reaction during RT. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Inhibitive effect on apoptosis in splenic lymphocytes of mice pretreated with lingzhi (Ganoderma lucidum) spores.

PubMed

Wang, Quanxi; Huang, Yifan; Wu, Baocheng; Mei, Jingliang; Zhang, Honglei; Qi, Baomin

2014-04-01

To investigate how the pretreatment of mice with Ganoderma spores affected the apoptosis of their splenic lymphocytes induced by dexamethasone after 19 days treatment. Sixty Kunming mice were randomly divided into six groups: blank control groupdrenched with normal saline; a drug control group drenched with 150 mg/mL Ganoderma spores; a model group treated with saline; a low dose group with 50 mg/mL Ganoderma spores; a moderate dose group with 100 mg/mL Ganoderma spores; and a high dose group with 150 mg/mL Ganoderma spores. The effect of Ganoderma spores on apoptosis in spleen lymphocytes was analyzed. All groups were treated for 19 days. On day 20, the model group and the 3 treatment groups were intraperitoneally injected dexamethasone to induce apoptosis. Splenic index and apoptosis indes were employed to measure cell apoptosis. The results showed that Ganoderma spores reduced the splenic index to different degrees in each group and the best effect was seen in the high dose group (P < 0.05).Terminal dexynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine 5'-Triphosphate nick end labeling staining revealed that the apoptotic index in all groups administered Ganoderma spores differed significantly from the model group, and a dose-response was observed. Flow cytometric analysis indicated that spleen lymphocyte apoptosis in the model group was extensive. Each dose of Ganoderma spores inhibited dexamethasone-induced apoptosis in spleen lymphocytes, and a dose-response was observed as well. The highest dose of Ganoderma spores decreased Malondialdehyde content in serum induced by dexamethasone (P < 0.05). The findings imply that the pretreatment of the mice with Ganoderma spores could reduce the apoptosis rate induced by dexamethasone in their splenic lymphocytes.

TU-D-209-03: Alignment of the Patient Graphic Model Using Fluoroscopic Images for Skin Dose Mapping

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

Oines, A; Oines, A; Kilian-Meneghin, J

2016-06-15

Purpose: The Dose Tracking System (DTS) was developed to provide realtime feedback of skin dose and dose rate during interventional fluoroscopic procedures. A color map on a 3D graphic of the patient represents the cumulative dose distribution on the skin. Automated image correlation algorithms are described which use the fluoroscopic procedure images to align and scale the patient graphic for more accurate dose mapping. Methods: Currently, the DTS employs manual patient graphic selection and alignment. To improve the accuracy of dose mapping and automate the software, various methods are explored to extract information about the beam location and patient morphologymore » from the procedure images. To match patient anatomy with a reference projection image, preprocessing is first used, including edge enhancement, edge detection, and contour detection. Template matching algorithms from OpenCV are then employed to find the location of the beam. Once a match is found, the reference graphic is scaled and rotated to fit the patient, using image registration correlation functions in Matlab. The algorithm runs correlation functions for all points and maps all correlation confidences to a surface map. The highest point of correlation is used for alignment and scaling. The transformation data is saved for later model scaling. Results: Anatomic recognition is used to find matching features between model and image and image registration correlation provides for alignment and scaling at any rotation angle with less than onesecond runtime, and at noise levels in excess of 150% of those found in normal procedures. Conclusion: The algorithm provides the necessary scaling and alignment tools to improve the accuracy of dose distribution mapping on the patient graphic with the DTS. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.« less

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

Persson, Mats, E-mail: mats.persson@mi.physics.kth

Purpose: The highest photon fluence rate that a computed tomography (CT) detector must be able to measure is an important parameter. The authors calculate the maximum transmitted fluence rate in a commercial CT scanner as a function of patient size for standard head, chest, and abdomen protocols. Methods: The authors scanned an anthropomorphic phantom (Kyoto Kagaku PBU-60) with the reference CT protocols provided by AAPM on a GE LightSpeed VCT scanner and noted the tube current applied with the tube current modulation (TCM) system. By rescaling this tube current using published measurements on the tube current modulation of a GEmore » scanner [N. Keat, “CT scanner automatic exposure control systems,” MHRA Evaluation Report 05016, ImPACT, London, UK, 2005], the authors could estimate the tube current that these protocols would have resulted in for other patient sizes. An ECG gated chest protocol was also simulated. Using measured dose rate profiles along the bowtie filters, the authors simulated imaging of anonymized patient images with a range of sizes on a GE VCT scanner and calculated the maximum transmitted fluence rate. In addition, the 99th and the 95th percentiles of the transmitted fluence rate distribution behind the patient are calculated and the effect of omitting projection lines passing just below the skin line is investigated. Results: The highest transmitted fluence rates on the detector for the AAPM reference protocols with centered patients are found for head images and for intermediate-sized chest images, both with a maximum of 3.4 ⋅ 10{sup 8} mm{sup −2} s{sup −1}, at 949 mm distance from the source. Miscentering the head by 50 mm downward increases the maximum transmitted fluence rate to 5.7 ⋅ 10{sup 8} mm{sup −2} s{sup −1}. The ECG gated chest protocol gives fluence rates up to 2.3 ⋅ 10{sup 8} − 3.6 ⋅ 10{sup 8} mm{sup −2} s{sup −1} depending on miscentering. Conclusions: The fluence rate on a CT detector reaches 3 ⋅ 10{sup 8} − 6 ⋅ 10{sup 8} mm{sup −2} s{sup −1} in standard imaging protocols, with the highest rates occurring for ECG gated chest and miscentered head scans. These results will be useful to developers of CT detectors, in particular photon counting detectors.« less

Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses.

PubMed

Aspenström-Fagerlund, Bitte; Nordkvist, Erik; Törnkvist, Anna; Wallgren, Per; Hoogenboom, Ron; Berendsen, Bjorn; Granelli, Kristina

2016-09-01

Toxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 μg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 μg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce;

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi;

Levels of daily light doses under changed day-night cycles regulate temporal segregation of photosynthesis and N2 Fixation in the cyanobacterium Trichodesmium erythraeum IMS101.

PubMed

Cai, Xiaoni; Gao, Kunshan

2015-01-01

While the diazotrophic cyanobacterium Trichodesmium is known to display inverse diurnal performances of photosynthesis and N2 fixation, such a phenomenon has not been well documented under different day-night (L-D) cycles and different levels of light dose exposed to the cells. Here, we show differences in growth, N2 fixation and photosynthetic carbon fixation as well as photochemical performances of Trichodesmium IMS101 grown under 12L:12D, 8L:16D and 16L:8D L-D cycles at 70 μmol photons m-2 s-1 PAR (LL) and 350 μmol photons m-2 s-1 PAR (HL). The specific growth rate was the highest under LL and the lowest under HL under 16L:8D, and it increased under LL and decreased under HL with increased levels of daytime light doses exposed under the different light regimes, respectively. N2 fixation and photosynthetic carbon fixation were affected differentially by changes in the day-night regimes, with the former increasing directly under LL with increased daytime light doses and decreased under HL over growth-saturating light levels. Temporal segregation of N2 fixation from photosynthetic carbon fixation was evidenced under all day-night regimes, showing a time lag between the peak in N2 fixation and dip in carbon fixation. Elongation of light period led to higher N2 fixation rate under LL than under HL, while shortening the light exposure to 8 h delayed the N2 fixation peaking time (at the end of light period) and extended it to night period. Photosynthetic carbon fixation rates and transfer of light photons were always higher under HL than LL, regardless of the day-night cycles. Conclusively, diel performance of N2 fixation possesses functional plasticity, which was regulated by levels of light energy supplies either via changing light levels or length of light exposure.

Arsenic hazard in Cambodian rice from a market-based survey with a case study of Preak Russey village, Kandal Province.

PubMed

Gilbert, Peter J; Polya, David A; Cooke, David A

2015-08-01

This study comprises a market-based survey to assess the arsenic (As) hazard of Cambodian rice, encompassing rice from seven Cambodian provinces, comparisons with rice imported from China, Vietnam and Thailand, and assessments of 15 rice varieties. Rice samples (n = 157) were collected from four large markets in Kandal Province and analysed for As using inductively coupled mass spectrometry. The mean As concentration for Cambodian rice (0.185 µg g(-1), range 0.047-0.771 µg g(-1)) was higher than that for imported rice from Vietnam and Thailand (0.162 and 0.157 µg g(-1), respectively) with mean As concentrations highest in rice from Prey Veng Province resulting in a daily dose of 1.77 µg kg(-1) b.w. (body weight) d(-1). Between unmilled rice varieties, Cambodian-grown White Sticky Rice had the highest mean As concentration (0.234 µg g(-1)), whilst White Sticky Rice produced in Thailand had the lowest (0.125 µg g(-1)), suggesting that localised conditions have greater bearing over rice As concentrations than differences in As uptake between individual varieties themselves. A rice and water consumption survey for 15 respondents in the village of Preak Russey revealed mean consumption rates of 522 g d(-1) of rice and 1.9 L d(-1) of water. At water As concentrations >1000 µg L(-1), the relative contribution to the daily dose from rice is low. When water As concentrations are lowered to 50 µg L(-1), daily doses from rice and water are both generally below the 3.0 µg kg(-1) b.w. d(-1) benchmark daily limit for a 0.5% increase in lung cancer, yet when combined they exceeded this value in all but three respondents.

Individual dose monitoring of the nuclear medicine departments staff controlled by Central Laboratory for Radiological Protection.

PubMed

Szewczak, Kamil; Jednoróg, Sławomir; Krajewski, Paweł

2013-01-01

Presented paper describes the results of the individual doses measurements for ionizing radiation, carried out by the Laboratory of Individual and Environmental Doses Monitoring (PDIS) of the Central Laboratory for Radiological Protection in Warsaw (CLOR) for the medical staff employees in several nuclear medicine (NM) departments across Poland. In total there are48 NM departments in operation in Poland [1] (consultation in Nuclear Atomic Agency). Presented results were collected over the period from January 2011 to December 2011 at eight NM departments located in Krakow, Warszawa (two departments), Rzeszow (two departments), Opole, Przemysl and Gorzow Wielkopolski. For radiation monitoring three kinds of thermo luminescence dosimeters (TLD) were used. The first TLD h collected information about whole body (C) effective dose, the second dosimeter was mounted in the ring (P) meanwhile the third on the wrist (N) of the tested person. Reading of TLDs was performed in quarterly periods. As a good approximation of effective and equivalent dose assessment of operational quantities both the individual dose equivalent Hp(10) and the Hp(0.07) were used. The analysis of the data was performed using two methods The first method was based on quarterly estimations of Hp(10)q and Hp(0.07)q while the second measured cumulative annual doses Hp(10)a and Hp(0.07)a. The highest recorded value of the radiation dose for quarterly assessments reached 24.4 mSv and was recorded by the wrist type dosimeter worn by a worker involved in source preparation procedure. The mean values of Hp(10)q(C type dosimeter) and Hp(0.07)q (P and N type dosimeter) for all monitored departments were respectively 0.46 mSv and 3.29 mSv. There was a strong correlation between the performed job and the value of the received dose. The highest doses always were absorbed by those staff members who were involved in sources preparation. The highest annual cumulative dose for a particular worker in the considered time period was 4.22 mSv for Hp(10)a and 67.7 mSv for Hp(0.07)a. In 2011 no case of exceeding the allowed dose limits was noted.

In vivo antimalarial activity of crude extracts and solvent fractions of leaves of Strychnos mitis in Plasmodium berghei infected mice.

PubMed

Fentahun, Selamawit; Makonnen, Eyasu; Awas, Tesfaye; Giday, Mirutse

2017-01-05

Malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-Saharan Africa. Today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. Medicinal plants are the unquestionable source of effective antimalarials. The present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant Strychnos mitis in Plasmodium berghei infected mice. Standard procedures were employed to investigate acute toxicity and 4-day suppressive effect of crude aqueous and hydro-methanolic extracts of the leaves of Strychnos mitis against P. berghei in Swiss albino mice. Water, n-hexane and chloroform fractions, obtained from crude hydro-methanolic extract, were also tested for their suppressive effect against P. berghei. All crude extracts revealed no obvious acute toxicity in mice up to the highest dose administered (2000 mg/kg). All crude and solvent fractions of the leaves of Strychnos mitis inhibited parasitaemia significantly (p < 0.01). At the highest dose of 600 mg/kg, both aqueous and hydro-methanolic extracts demonstrated higher performance with 95.5 and 93.97% parasitaemia suppression, respectively. All doses of crude extracts and fractions of leaves of Strychnos mitis prolonged survival time of infected mice dose dependently. The highest two doses of the crude aqueous and hydro-methanolic extracts, and chloroform and aqueous fractions prevented weight loss in a dose dependent manner. Whereas, all doses of n-hexane fraction prevented loss of body weight but not in a dose dependent manner. The crude aqueous extract at the doses of 400 mg/kg and 600 mg/kg and hydro-methanolic extract at all dose levels significantly (p < 0.01) prevented packed cell volume reduction. Crude aqueous extract at a dose of 600 mg/kg and hydro-methanolic extract at all dose levels significantly prevented temperature reduction. Phytochemical screening of the crude aqueous and hydro-methanolic extracts revealed the presence of alkaloids, anthraquinones, glycosides, terpenoids, saponins, tannins and phenols. The results of this study provide support the traditional therapeutic use of Strychnos mitis for treatment of malaria. However, further in-depth study is needed to evaluate the potential of the plant towards the development of new antimalarial agent.

Committed effective dose determination in southern Brazilian cereal flours.

PubMed

Scheibel, V; Appoloni, C R

2013-01-01

The health impact of radionuclide ingestion from foodstuffs was evaluated by the committed effective doses determined in eight commercial samples of South-Brazilian cereal flours (soy, wheat, cornmeal, cassava, rye, oat, barley and rice flours). The radioactivity traces of (228)Th, (228)Ra, (226)Ra, (40)K, (7)Be and (137)Cs were measured by gamma-ray spectrometry employing an HPGe detector of 66 % relative efficiency. The efficiency curve has taken into account the differences in densities and chemical composition between the matrix and the certified sample. The highest concentration levels of (228)Th and (40)K were 3.5±0.4 and 1469±17 Bq kg(-1) for soy flour, respectively, within the 95 % confidence level. The lower limit of detection for (137)Cs ranged from 0.04 to 0.4 Bq kg(-1). The highest committed effective dose was 0.36 μSv.y(-1) for (228)Ra in cassava flour (adults). All committed effective doses determined at the present work were lower than the International Atomic Energy Agency dose limit of 1 mSv.y(-1), to the public exposure.

Serum high density lipoprotein cholesterol, alcohol, and coronary mortality in male smokers.

PubMed Central

Paunio, M.; Virtamo, J.; Gref, C. G.; Heinonen, O. P.

1996-01-01

OBJECTIVE--To determine whether the increase in mortality from coronary heart disease with high concentration (> 1.75 mmol/l) of high density lipoprotein cholesterol could be due to alcohol intake. DESIGN--Cohort study. SETTING--Placebo group of the alpha tocopherol, beta carotene cancer prevention (ATBC) study of south western population in Finland. PARTICIPANTS--7052 male smokers aged 50-69 years enrolled to the ATBC study in the 1980s. MAIN OUTCOME MEASURES--The relative and absolute rates adjusted for risk factors for clinically or pathologically verified deaths from coronary heart disease for different concentrations of high density lipoprotein cholesterol with and without stratification for alcohol intake. Similar rates were also calculated for different alcohol consumption groups. RESULTS--During the average follow up period of 6.7 years 258 men died from verified coronary heart disease. Coronary death rate steadily decreased with increasing concentration of high density lipoprotein cholesterol until a high concentration. An increase in the rate was observed above 1.75 mmol/l. This increase occurred among those who reported alcohol intake. Mortality was associated with alcohol intake in a J shaped dose response, and those who reported consuming more than five drinks a day (heavy drinkers) had the highest death rate. Mortality was higher in heavy drinkers than in non-drinkers or light or moderate drinkers in all high density lipoprotein categories from 0.91 mmol/l upward. CONCLUSIONS--Mortality from coronary heart disease increases at concentrations of high density lipoprotein cholesterol over 1.75 mmol/l. The mortality was highest among heavy drinkers, but an increase was found among light drinkers also. PMID:8634563

RadNuc: A graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator

PubMed Central

Pasternack, Jordan B.; Howell, Roger W.

2012-01-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy are generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Methods Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. Results The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/hr and a minimum dose rate of 0.01 cGy/hr. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/hr. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. Conclusion The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. PMID:23265668

RadNuc: a graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator.

PubMed

Pasternack, Jordan B; Howell, Roger W

2013-02-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy is generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/h and a minimum dose rate of 0.01 cGy/h. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/h. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

Frame average optimization of cine-mode EPID images used for routine clinical in vivo patient dose verification of VMAT deliveries

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

McCowan, P. M., E-mail: pmccowan@cancercare.mb.ca; McCurdy, B. M. C.; Medical Physics Department, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba R3E 0V9

Purpose: The in vivo 3D dose delivered to a patient during volumetric modulated arc therapy (VMAT) delivery can be calculated using electronic portal imaging device (EPID) images. These images must be acquired in cine-mode (i.e., “movie” mode) in order to capture the time-dependent delivery information. The angle subtended by each cine-mode EPID image during an arc can be changed via the frame averaging number selected within the image acquisition software. A large frame average number will decrease the EPID’s angular resolution and will result in a decrease in the accuracy of the dose information contained within each image. Alternatively, lessmore » EPID images acquired per delivery will decrease the overall 3D patient dose calculation time, which is appealing for large-scale clinical implementation. Therefore, the purpose of this study was to determine the optimal frame average value per EPID image, defined as the highest frame averaging that can be used without an appreciable loss in 3D dose reconstruction accuracy for VMAT treatments. Methods: Six different VMAT plans and six different SBRT-VMAT plans were delivered to an anthropomorphic phantom. Delivery was carried out on a Varian 2300ix model linear accelerator (Linac) equipped with an aS1000 EPID running at a frame acquisition rate of 7.5 Hz. An additional PC was set up at the Linac console area, equipped with specialized frame-grabber hardware and software packages allowing continuous acquisition of all EPID frames during delivery. Frames were averaged into “frame-averaged” EPID images using MATLAB. Each frame-averaged data set was used to calculate the in vivo dose to the patient and then compared to the single EPID frame in vivo dose calculation (the single frame calculation represents the highest possible angular resolution per EPID image). A mean percentage dose difference of low dose (<20% prescription dose) and high dose regions (>80% prescription dose) was calculated for each frame averaged scenario for each plan. The authors defined their unacceptable loss of accuracy as no more than a ±1% mean dose difference in the high dose region. Optimal frame average numbers were then determined as a function of the Linac’s average gantry speed and the dose per fraction. Results: The authors found that 9 and 11 frame averages were suitable for all VMAT and SBRT-VMAT treatments, respectively. This resulted in no more than a 1% loss to any of the dose region’s mean percentage difference when compared to the single frame reconstruction. The optimized number was dependent on the treatment’s dose per fraction and was determined to be as high as 14 for 12 Gy/fraction (fx), 15 for 8 Gy/fx, 11 for 6 Gy/fx, and 9 for 2 Gy/fx. Conclusions: The authors have determined an optimal EPID frame averaging number for multiple VMAT-type treatments. These are given as a function of the dose per fraction and average gantry speed. These optimized values are now used in the authors’ clinical, 3D, in vivo patient dosimetry program. This provides a reduction in calculation time while maintaining the authors’ required level of accuracy in the dose reconstruction.« less

Effect of Bt-176 maize pollen on first instar larvae of the Peacock butterfly (Inachis io) (Lepidoptera; Nymphalidae).

PubMed

Felke, Martin; Langenbruch, Gustav-Adolf; Feiertag, Simon; Kassa, Adane

2010-01-01

More than 10 years after registration of the first Bt maize cultivar in Europe, there still exists a remarkable lack of data on effects on Lepidoptera which would be necessary for a complete and comprehensive environmental risk assessment. So far only very few European butterfly species have been tested in this aspect. In our study the effect of transgenic Bacillus thuringiensis (Bt) maize pollen (event Bt-176) on the development and survival of neonate larvae of the Peacock butterfly, Inachis io (L.) was for the first time shown. The results of our study suggest that the Peacock butterfly may serve as a model organism for assessing potential side effects of new developed transgenic Bt crops on non-target butterflies in a GMO environmental risk assessment. The study was done under laboratory conditions by exposing larvae of the Peacock butterfly to various pollen doses of transgenic maize event Bt-176 (cv. PACTOL CB) or the conventional isogenic maize (cv. PACTOL) using a no-choice test. Larvae feeding for 48 h on nettle plants (Urtica dioica) that were contaminated with higher pollen concentrations from Bt-176 maize (205 and 388 applied pollen.cm⁻²) suffered a significantly higher mortality rate (68 and 85% respectively) compared to larvae feeding on leaves with no pollen (11%), or feeding on leaves with pollen from conventional maize (6 to 25%). At lower Bt maize pollen doses (23-104 applied pollen.cm⁻²),mortality ranged from 11-25% and there were no apparent differences among treatments. The corresponding LC₅₀-and LC₉₀-values for neonate larvae of the Peacock butterfly were 187 and 448 applied pollen grains.cm⁻² of Bt-176, respectively.Weight of larvae surviving consumption of Bt-176 maize pollen declined between 10 and 81% with increased pollen doses (r = -0.95). The highest weight reduction (81%) corresponded to the highest pollen concentration (388 pollen grains applied.cm⁻²). Ingestion of pollen from the conventional maize hybrid did not have negative effects on larval weight gain or survival rate.

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

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

Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.

2012-08-01

Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADTmore » and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.« less

The LILIA experiment: Energy selection and post-acceleration of laser generated protons

NASA Astrophysics Data System (ADS)

Turchetti, Giorgio; Sinigardi, Stefano; Londrillo, Pasquale; Rossi, Francesco; Sumini, Marco; Giove, Dario; De Martinis, Carlo

2012-12-01

The LILIA experiment is planned at the SPARCLAB facility of the Frascati INFN laboratories. We have simulated the laser acceleration of protons, the transport and energy selection with collimators and a pulsed solenoid and the post-acceleration with a compact high field linac. For the highest achievable intensity corresponding to a = 30 over 108 protons at 30 MeV with a 3% spread are selected, and at least107 protons are post-accelerated up to 60 MeV. If a 10 Hz repetition rated can be achieved the delivered dose would be suitable for the treatment of small superficial tumors.

Response ofMeteorus leviventris, (Hymenoptera: Braconidae) to mustard oils in field trapping experiments.

PubMed

Pivnick, K A

1993-09-01

Trapping experiments were carried out near Saskatoon, Canada, from May through August 1990 to assess the response of the braconid wasp,Meteorus leviventris, to four selected mustard oils or isothiocyanates (IC) at a release rate of 4 mg/day, and for allyl IC only, at 40 mg/day. Only allyl IC at 4 mg/day was significantly attractive when trap captures were compared to the captures in the control traps. The others (n-propyl IC, 2-phenylethyl IC., and ethyl IC) were not attractive, nor was allyl IC at the higher dose, although trap captures with the latter bait were the second highest.

Evaluation of an X-Ray Dose Profile Derived from an Optically Stimulated Luminescent Dosimeter during Computed Tomographic Fluoroscopy.

PubMed

Hasegawa, Hiroaki; Sato, Masanori; Tanaka, Hiroshi

2015-01-01

The purpose of this study was to evaluate scatter radiation dose to the subject surface during X-ray computed tomography (CT) fluoroscopy using the integrated dose ratio (IDR) of an X-ray dose profile derived from an optically stimulated luminescent (OSL) dosimeter. We aimed to obtain quantitative evidence supporting the radiation protection methods used during previous CT fluoroscopy. A multislice CT scanner was used to perform this study. OSL dosimeters were placed on the top and the lateral side of the chest phantom so that the longitudinal direction of dosimeters was parallel to the orthogonal axis-to-slice plane for measurement of dose profiles in CT fluoroscopy. Measurement of fluoroscopic conditions was performed at 120 kVp and 80 kVp. Scatter radiation dose was evaluated by calculating the integrated dose determined by OSL dosimetry. The overall percent difference of the integrated doses between OSL dosimeters and ionization chamber was 5.92%. The ratio of the integrated dose of a 100-mm length area to its tails (-50 to -6 mm, 50 to 6 mm) was the lowest on the lateral side at 80 kVp and the highest on the top at 120 kVp. The IDRs for different measurement positions were larger at 120 kVp than at 80 kVp. Similarly, the IDRs for the tube voltage between the primary X-ray beam and scatter radiation was larger on the lateral side than on the top of the phantom. IDR evaluation suggested that the scatter radiation dose has a high dependence on the position and a low dependence on tube voltage relative to the primary X-ray beam for constant dose rate fluoroscopic conditions. These results provided quantitative evidence supporting the radiation protection methods used during CT fluoroscopy in previous studies.

Evaluation of an X-Ray Dose Profile Derived from an Optically Stimulated Luminescent Dosimeter during Computed Tomographic Fluoroscopy

PubMed Central

Hasegawa, Hiroaki; Sato, Masanori; Tanaka, Hiroshi

2015-01-01

The purpose of this study was to evaluate scatter radiation dose to the subject surface during X-ray computed tomography (CT) fluoroscopy using the integrated dose ratio (IDR) of an X-ray dose profile derived from an optically stimulated luminescent (OSL) dosimeter. We aimed to obtain quantitative evidence supporting the radiation protection methods used during previous CT fluoroscopy. A multislice CT scanner was used to perform this study. OSL dosimeters were placed on the top and the lateral side of the chest phantom so that the longitudinal direction of dosimeters was parallel to the orthogonal axis-to-slice plane for measurement of dose profiles in CT fluoroscopy. Measurement of fluoroscopic conditions was performed at 120 kVp and 80 kVp. Scatter radiation dose was evaluated by calculating the integrated dose determined by OSL dosimetry. The overall percent difference of the integrated doses between OSL dosimeters and ionization chamber was 5.92%. The ratio of the integrated dose of a 100-mm length area to its tails (−50 to −6 mm, 50 to 6 mm) was the lowest on the lateral side at 80 kVp and the highest on the top at 120 kVp. The IDRs for different measurement positions were larger at 120 kVp than at 80 kVp. Similarly, the IDRs for the tube voltage between the primary X-ray beam and scatter radiation was larger on the lateral side than on the top of the phantom. IDR evaluation suggested that the scatter radiation dose has a high dependence on the position and a low dependence on tube voltage relative to the primary X-ray beam for constant dose rate fluoroscopic conditions. These results provided quantitative evidence supporting the radiation protection methods used during CT fluoroscopy in previous studies. PMID:26151914

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer.

PubMed

Wen, Ning; Guan, Huaiqun; Hammoud, Rabih; Pradhan, Deepak; Nurushev, T; Li, Shidong; Movsas, Benjamin

2007-04-21

With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patient's skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patient's tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was approximately 4.0 cGy, which was approximately 40% higher than the Rt Lat dose of approximately 2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm x 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patient's Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370 degrees scan rotation (10 degrees scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of approximately 10-11 cGy while the right hip received approximately 6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than approximately 12% to the table-drop setup.

Dose delivered from Varian's CBCT to patients receiving IMRT for prostate cancer

NASA Astrophysics Data System (ADS)

Wen, Ning; Guan, Huaiqun; Hammoud, Rabih; Pradhan, Deepak; Nurushev, T.; Li, Shidong; Movsas, Benjamin

2007-04-01

With the increased use of cone beam CT (CBCT) for daily patient setup, the accumulated dose from CBCT may be significantly higher than that from simulation CT or portal imaging. The objective of this work is to measure the dose from daily pelvic scans with fixed technical settings and collimations. CBCT scans were acquired in half-fan mode using a half bowtie and x-rays were delivered in pulsed-fluoro mode. The skin doses for seven prostate patients were measured on an IRB-approved protocol. TLD capsules were placed on the patient's skin at the central axis of three beams: AP, left lateral (Lt Lat) and right lateral (Rt Lat). To avoid the ring artefacts centred in the prostate, the treatment couch was dropped 3 cm from the patient's tattoo (central axis). The measured AP skin doses ranged 3-6 cGy for 20-33 cm separation. The larger the patient size the less the AP skin dose. Lateral doses did not change much with patient size. The Lt Lat dose was ~4.0 cGy, which was ~40% higher than the Rt Lat dose of ~2.6 cGy. To verify this dose asymmetry, surface doses on an IMRT QA phantom (oval shaped, 30 cm × 20 cm) were measured at the same three sites using TLD capsules with 3 cm table-drop. The dose asymmetry was due to: (1) kV source rotation which always starts from the patient's Lt Lat and ends at Lt Lat. Gantry rotation gets much slower near the end of rotation but dose rate stays constant and (2) 370° scan rotation (10° scan overlap on the Lt Lat side). In vivo doses were measured inside a Rando pelvic heterogeneous phantom using TLDs. The left hip (femoral head and neck) received the highest doses of ~10-11 cGy while the right hip received ~6-7 cGy. The surface and in vivo doses were also measured for phantoms at the central-axis setup. The difference was less than ~12% to the table-drop setup.

Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

PubMed

Hannoun-Lévi, J-M; Peiffert, D

2014-10-01

Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline

PubMed Central

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O’Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C.; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M.; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-01-01

Purpose To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. Methods The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Results Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. Recommendations In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus–related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines. PMID:29094100

Effects of maternal and lactational exposure to 2-hydroxy-4-methoxybenzone on development and reproductive organs in male and female rat offspring

PubMed Central

Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Chang, Ching-Wei; Trbojevich, Raul A.; Sepehr, Estatira; Voris, Kristie L.; Patton, Ralph E.; Bryant, Matthew S.; Harrouk, Wafa; McIntyre, Barry; Foster, Paul M.; Hansen, Deborah K.

2015-01-01

BACKGROUND 2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV)-absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential. METHODS To determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1,000, 3,000, 10,000, 25,000, or 50,000 ppm HMB (7-8 per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23. RESULTS AND CONCLUSION Exposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats. PMID:25707689

Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration

PubMed Central

2014-01-01

Background Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Methods Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls. During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. Results There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Conclusions Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg. PMID:24606886

Assessing dose rate distributions in VMAT plans

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2016-04-01

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min-1 for conventional fractionation.

Changes in dialysis treatment modalities during institution of flat rate reimbursement and quality assurance programs.

PubMed

Kleophas, Werner; Karaboyas, Angelo; Li, Yun; Bommer, Juergen; Reichel, Helmut; Walter, Andreas; Icks, Andrea; Rump, Lars C; Pisoni, Ronald L; Robinson, Bruce M; Port, Friedrich K

2013-09-01

Dialysis procedure rates in Germany were changed in 2002 from per-session to weekly flat rate payments, and quality assurance was introduced in 2009 with defined treatment targets for spKt/V, dialysis frequency, treatment time, and hemoglobin. In order to understand trends in treatment parameters before and after the introduction of these changes, we analyzed data from 407 to 618 prevalent patients each year (hemodialysis over 90 days) in 14-21 centers in cross-sections of the Dialysis Outcomes and Practice Patterns Study (phases 1-4, 1998-2011). Descriptive statistics were used to report differences over time in the four quality assurance parameters along with erythropoietin-stimulating agent (ESA) and intravenous iron doses. Time trends were analyzed using linear mixed models adjusted for patient demographics and comorbidities. The proportion of patients with short treatment times (less than 4 h) and low spKt/V (below 1.2) improved throughout the study and was lowest after implementation of quality assurance. Hemoglobin levels have increased since 1998 and remained consistent since 2005, with only 8-10% of patients below 10 g/dl. About 90% of patients were prescribed ESAs, with the dose declining since peaking in 2006. Intravenous iron use was highest in 2011. Hence, trends to improve quality metrics for hemodialysis have been established in Germany even after introduction of flat rate reimbursement. Thus, analysis of facility practice patterns is needed to maintain quality of care in a cost-containment environment.

Oxidative elimination of cyanotoxins: comparison of ozone, chlorine, chlorine dioxide and permanganate.

PubMed

Rodríguez, Eva; Onstad, Gretchen D; Kull, Tomas P J; Metcalf, James S; Acero, Juan L; von Gunten, Urs

2007-08-01

As the World Health Organization (WHO) progresses with provisional Drinking Water Guidelines of 1 microg/L for microcystin-LR and a proposed Guideline of 1 microg/L for cylindrospermopsin, efficient treatment strategies are needed to prevent cyanotoxins such as these from reaching consumers. A kinetic database has been compiled for the oxidative treatment of three cyanotoxins: microcystin-LR (MC-LR), cylindrospermopsin (CYN), and anatoxin-a (ANTX) with ozone, chlorine, chlorine dioxide and permanganate. This kinetic database contains rate constants not previously reported and determined in the present work (e.g. for permanganate oxidation of ANTX and chlorine dioxide oxidation of CYN and ANTX), together with previously published rate constants for the remaining oxidation processes. Second-order rate constants measured in pure aqueous solutions of these toxins could be used in a kinetic model to predict the toxin oxidation efficiency of ozone, chlorine, chlorine dioxide and permanganate when applied to natural waters. Oxidants were applied to water from a eutrophic Swiss lake (Lake Greifensee) in static-dose testing and dynamic time-resolved experiments to confirm predictions from the kinetic database, and to investigate the effects of a natural matrix on toxin oxidation and by-product formation. Overall, permanganate can effectively oxidize ANTX and MC-LR, while chlorine will oxidize CYN and MC-LR and ozone is capable of oxidizing all three toxins with the highest rate. The formation of trihalomethanes (THMs) in the treated water may be a restriction to the application of sufficiently high-chlorine doses.

Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer.

PubMed

Eisbruch, Avraham; Ship, Jonathan A; Dawson, Laura A; Kim, Hyungjin M; Bradford, Carol R; Terrell, Jeffrey E; Chepeha, Douglas B; Teknos, Theodore N; Hogikyan, Norman D; Anzai, Yoshimi; Marsh, Lon H; Ten Haken, Randall K; Wolf, Gregory T

2003-07-01

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

State variation in rates of cesarean and VBAC delivery: 1989 and 1993.

PubMed

Clarke, S C; Taffel, S M

1996-01-01

There is wide variation among states in rates of cesarean and vaginal births after cesarean (VBAC) deliveries. In general, states in the South have the highest cesarean rates, states in the West have the lowest, and states in the Northeast and Midwest are intermediate. Louisiana had the highest overall rate in 1993 (27.7 per 100 births) while Alaska had the lowest rate (15.2). The majority of states had declines in their cesarean rate between 1989 and 1993. Patterns in primary cesarean rates are similar to those of the overall rate-states in the South generally have the highest rates while states in the West have the lowest rates. Primary cesarean rates ranged between a high of 19.6 in Louisiana to a low of 10.6 in Wisconsin. In general, states with low cesarean rates have among the highest rates of VBAC delivery. Alaska had the highest VBAC rate (40.0), which was almost quadruple the rate of Louisiana (11.2), the state with the lowest rate. Most states had substantial increases in VBAC rates between 1989 and 1993. When examining cesarean rates by maternal age and birth order, states with the highest overall rates also have among the highest age/birth order-specific rates. Cesarean rates were lowest for mothers under 25 years of age having a second or higher order birth in Alaska, 10.4, and highest for mothers 35 years of age or over having a first birth in Mississippi, 51.3. Standardized cesarean rates which were adjusted for differences between states in maternal age and birth order distributions did not diminish the variation among areas.

Intensity-modulated radiation therapy and volumetric-modulated arc therapy for adult craniospinal irradiation—A comparison with traditional techniques

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

Studenski, Matthew T., E-mail: matthew.studenski@jeffersonhospital.org; Shen, Xinglei; Yu, Yan

2013-04-01

Craniospinal irradiation (CSI) poses a challenging planning process because of the complex target volume. Traditional 3D conformal CSI does not spare any critical organs, resulting in toxicity in patients. Here the dosimetric advantages of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) are compared with classic conformal planning in adults for both cranial and spine fields to develop a clinically feasible technique that is both effective and efficient. Ten adult patients treated with CSI were retrospectively identified. For the cranial fields, 5-field IMRT and dual 356° VMAT arcs were compared with opposed lateral 3D conformal radiotherapy (3D-CRT) fields. Formore » the spine fields, traditional posterior-anterior (PA) PA fields were compared with isocentric 5-field IMRT plans and single 200° VMAT arcs. Two adult patients have been treated using this IMRT technique to date and extensive quality assurance, especially for the junction regions, was performed. For the cranial fields, the IMRT technique had the highest planned target volume (PTV) maximum and was the least efficient, whereas the VMAT technique provided the greatest parotid sparing with better efficiency. 3D-CRT provided the most efficient delivery but with the highest parotid dose. For the spine fields, VMAT provided the best PTV coverage but had the highest mean dose to all organs at risk (OAR). 3D-CRT had the highest PTV and OAR maximum doses but was the most efficient. IMRT provides the greatest OAR sparing but the longest delivery time. For those patients with unresectable disease that can benefit from a higher, definitive dose, 3D-CRT–opposed laterals are the most clinically feasible technique for cranial fields and for spine fields. Although inefficient, the IMRT technique is the most clinically feasible because of the increased mean OAR dose with the VMAT technique. Quality assurance of the beams, especially the junction regions, is essential.« less

Detailed source term estimation of atmospheric release during the Fukushima Dai-ichi nuclear power plant accident by coupling atmospheric and oceanic dispersion models

NASA Astrophysics Data System (ADS)

Katata, Genki; Chino, Masamichi; Terada, Hiroaki; Kobayashi, Takuya; Ota, Masakazu; Nagai, Haruyasu; Kajino, Mizuo

2014-05-01

Temporal variations of release amounts of radionuclides during the Fukushima Dai-ichi Nuclear Power Plant (FNPP1) accident and their dispersion process are essential to evaluate the environmental impacts and resultant radiological doses to the public. Here, we estimated a detailed time trend of atmospheric releases during the accident by combining environmental monitoring data and coupling atmospheric and oceanic dispersion simulations by WSPEEDI-II (Worldwide version of System for Prediction of Environmental Emergency Dose Information) and SEA-GEARN developed by the authors. New schemes for wet, dry, and fog depositions of radioactive iodine gas (I2 and CH3I) and other particles (I-131, Te-132, Cs-137, and Cs-134) were incorporated into WSPEEDI-II. The deposition calculated by WSPEEDI-II was used as input data of ocean dispersion calculations by SEA-GEARN. The reverse estimation method based on the simulation by both models assuming unit release rate (1 Bq h-1) was adopted to estimate the source term at the FNPP1 using air dose rate, and air sea surface concentrations. The results suggested that the major release of radionuclides from the FNPP1 occurred in the following periods during March 2011: afternoon on the 12th when the venting and hydrogen explosion occurred at Unit 1, morning on the 13th after the venting event at Unit 3, midnight on the 14th when several openings of SRV (steam relief valve) were conducted at Unit 2, morning and night on the 15th, and morning on the 16th. The modified WSPEEDI-II using the newly estimated source term well reproduced local and regional patterns of air dose rate and surface deposition of I-131 and Cs-137 obtained by airborne observations. Our dispersion simulations also revealed that the highest radioactive contamination areas around FNPP1 were created from 15th to 16th March by complicated interactions among rainfall (wet deposition), plume movements, and phase properties (gas or particle) of I-131 and release rates associated with reactor pressure variations in Units 2 and 3.

A Phase 1 trial of the PARP inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer

PubMed Central

Liu, Joyce F.; Tolaney, Sara M.; Birrer, Michael; Fleming, Gini F.; Buss, Mary K.; Dahlberg, Suzanne E.; Lee, Hang; Whalen, Christin; Tyburski, Karin; Winer, Eric; Ivy, Percy; Matulonis, Ursula A.

2014-01-01

Background PARP-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of VEGFR-1/2/3, and olaparib, a PARP-inhibitor (NCT01116648). Methods Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by RECIST 1.1 or met GCIG CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. Results 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 DLTs (1 grade 4 neutropenia ≥4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30mg daily; olaparib 400mg BID). The RP2D was cediranib 30mg daily and olaparib 200mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus SD >24 weeks) of 61%. None of the 7 evaluable breast cancer patients achieved clinical response; 2 patients had stable disease for >24 weeks. Interpretation The combination of cediranib and olaparib has hematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. PMID:23810467

Role of dopamine transporters in the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in nonhuman primates

PubMed Central

Fantegrossi, William E.; Bauzo, Rayna M.; Manvich, Daniel M.; Morales, Jose C.; Votaw, John R.; Goodman, Mark M.

2011-01-01

Rationale The interoceptive and reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA) are similar to those of psychostimulants, but the role of dopamine in the behavioral effects of MDMA is not well documented, especially in primates. Objective The aim of this study was to assess the role of dopamine in the behavioral effects of MDMA in two nonhuman primate species. Methods The behavioral effects of MDMA, with and without serotonergic or dopaminergic pretreatments, were studied in squirrel monkeys trained to respond under a fixed-interval schedule of stimulus termination; effects on caudate dopamine levels were studied in a separate group of squirrel monkeys using in vivo microdialysis. Positron emission tomography neuroimaging with the dopamine transporter (DAT) ligand [18F]FECNT was used to determine DAT occupancy by MDMA in rhesus monkeys. Results MDMA (0.5–1.5 mg/kg) did not induce behavioral stimulant effects, but the highest dose of MDMA suppressed responding. Pretreatment with fluoxetine (3.0 mg/kg) or the selective 5HT2A antagonist M100907 (0.03–0.3 mg/kg) attenuated the rate suppressing effects of MDMA. In contrast, pretreatment with the selective dopamine transporter inhibitor RTI-177 (0.1 mg/kg) did not alter the rate suppressing effects of MDMA. Administration of MDMA at a dose that suppressed operant behavior had negligible effects on extracellular dopamine. The percent DAT occupancy of MDMA at a dose that suppressed operant behavior also was marginal and reflected low in vivo potency for DAT binding. Conclusions Collectively, these results indicate that behaviorally relevant doses of MDMA do not induce behavioral stimulant or dopamine transporter-mediated effects in nonhuman primates. PMID:19421742

Role of dopamine transporters in the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in nonhuman primates.

PubMed

Fantegrossi, William E; Bauzo, Rayna M; Manvich, Daniel M; Morales, Jose C; Votaw, John R; Goodman, Mark M; Howell, Leonard L

2009-08-01

The interoceptive and reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA) are similar to those of psychostimulants, but the role of dopamine in the behavioral effects of MDMA is not well documented, especially in primates. The aim of this study was to assess the role of dopamine in the behavioral effects of MDMA in two nonhuman primate species. The behavioral effects of MDMA, with and without serotonergic or dopaminergic pretreatments, were studied in squirrel monkeys trained to respond under a fixed-interval schedule of stimulus termination; effects on caudate dopamine levels were studied in a separate group of squirrel monkeys using in vivo microdialysis. Positron emission tomography neuroimaging with the dopamine transporter (DAT) ligand [18F]FECNT was used to determine DAT occupancy by MDMA in rhesus monkeys. MDMA (0.5-1.5 mg/kg) did not induce behavioral stimulant effects, but the highest dose of MDMA suppressed responding. Pretreatment with fluoxetine (3.0 mg/kg) or the selective 5HT(2A) antagonist M100907 (0.03-0.3 mg/kg) attenuated the rate suppressing effects of MDMA. In contrast, pretreatment with the selective dopamine transporter inhibitor RTI-177 (0.1 mg/kg) did not alter the rate suppressing effects of MDMA. Administration of MDMA at a dose that suppressed operant behavior had negligible effects on extracellular dopamine. The percent DAT occupancy of MDMA at a dose that suppressed operant behavior also was marginal and reflected low in vivo potency for DAT binding. Collectively, these results indicate that behaviorally relevant doses of MDMA do not induce behavioral stimulant or dopamine transporter-mediated effects in nonhuman primates.

St. Louis Airport Site. Annual site environmental report, calendar year 1985. Formerly Utilized Sites Remedial Action Program (FUSRAP). Revision 1

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

Not Available

1986-09-01

During 1985, the environmental monitoring program was continued at the St. Louis Airport Site (SLAPS) in St. Louis County, Missouri. The ditches north and south of the site have been designated for cleanup as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP). The monitoring program at the SLAPS measures radon gas concentrations in air; external gamma radiation dose rates; and uranium, thorium, and radium concentrations in surface water, groundwater, and sediment. Potential radiation doses to the public are also calculated. Because the site is not controlled or regulated by the DOE, the DOE Derived Concentration Guides (DCGs) aremore » not applicable to SLAPS, but are included only as a basis for comparison. The DOE DCGs and the DOE radiation protection standard have been revised. (Appendix B). During 1985, annual average radon levels in air at the SLAPS were below the DCG for uncontrolled areas. External gamma monitoring in 1985 showed measured annual gamma dose rates ranging from 3 to 2087 mrem/y, with the highest value occurring in an area known to be contaminated. The calculated maximum dose at the site boundary, assuming limited occupancy, would be 6 mrem/y. Average annual concentrations of /sup 230/Th, /sup 226/Ra, and total uranium in surface waters remained below the DOE DCG. The on-site groundwater measurements showed that average annual concentrations of /sup 230/Th, /sup 226/Ra and total uranium were within the DOE DCGs. Although there are no DCGs for sediments, all concentrations of total uraniu, /sup 230/Th, and /sup 226/Ra were below the FUSRAP Guidelines.« less

Side Effects of Standard Adjuvant and Neoadjuvant Chemotherapy Regimens According to Age Groups in Primary Breast Cancer

PubMed Central

Reinisch, Mattea; von Minckwitz, Gunter; Harbeck, Nadia; Janni, Wolfgang; Kümmel, Sherko; Kaufmann, Manfred; Elling, Dirk; Nekljudova, Valentina; Loibl, Sibylle

2013-01-01

Summary Background Elderly breast cancer patients are underrepresented in clinical trials and this leads to a lack of knowledge regarding the tolerance and side effects of modern chemotherapy regimens, especially in dose-dense (dd) or dose-intensified combination. Patients and Methods In this analysis, data from 4 German, randomized (neo-)adjuvant trials, including anthracycline-based chemotherapy, were evaluated for toxicity, compliance and feasibility. Patients were grouped according to age. Results Of the 4,775 patients, 73.6% were < 60 years, 15.8% were 60–64 years and 10.6% were > 64 years. The patients’ compliance decreased with increasing age, the rate of therapy discontinuations was 10.3%; 16.0% were > 64 years old (p < 0.001). The rate of dose reductions also increased with increasing age in the docetaxel/doxorubicin/cyclophosphamide (TAC) (p overall = 0.02) and 5-fluorouracil/epirubicin-cyclophosphamide (FE120C) (p overall < 0.001) treatment groups. Neutropenia grade 3 + 4 in patients of > 64 years was 77% in FE120C- compared to 55% in TAC-treated patients (with primary granulocyte colony-stimulating factors (G-CSFs)). The incidence of febrile neutropenia (FN) was lowest in the regimens without additional taxanes. FN in patients aged > 64 years was lower in the FE120C- than in TAC-and dd-doxorubicin/docetaxel-treated groups. Conclusion The range and intensity of toxicity increased with age. Neutropenia did not increase significantly in the dd groups; the highest rate was seen in FE120C-treated patients. FE120C without G-CSFs is not an option in patients older than 64 years. PMID:24715845

Influences of DMP on the Fertilization Process and Subsequent Embryogenesis of Abalone (Haliotis diversicolor supertexta) by Gametes Exposure

PubMed Central

Cai, Zhong-Hua

2011-01-01

Di-methyl phthalate (DMP), a typical endocrine disrupting chemical (EDC), is ubiquitously distributed in aquatic environments; yet studies regarding its impact on gametes and the resulting effects on embryogenesis in marine gastropods are relatively scarce. In this study, the influences of DMP on the gametes and subsequent developmental process of abalone (Haliotis diversicolor supertexta, a representative marine benthic gastropod) were assessed. Newborn abalone eggs and sperm were exposed separately to different DMP concentrations (1, 10 or 100 ppb) for 60 min. At the end-point of exposure, the DMP-treated eggs and sperm were collected for analysis of their ultra-structures, ATPase activities and total lipid levels, and the fertilized gametes (embryos) were collected to monitor related reproductive parameters (fertilization rate, abnormal development rate and hatching success rate). Treatment with DMP did not significantly alter the structure or total lipid content of eggs at any of the doses tested. Hatching failures and morphological abnormalities were only observed with the highest dose of DMP (100 ppb). However, DMP exposure did suppress sperm ATPase activities and affect the morphological character of their mitochondria. DMP-treated sperm exhibited dose-dependent decreases in fertilization efficiency, morphogenesis and hatchability. Relatively obvious toxicological effects were observed when both sperm and eggs were exposed to DMP. Furthermore, RT-PCR results indicate that treatment of gametes with DMP changed the expression patterns of physiologically-regulated genes (cyp3a, 17β-HSD-11 and 17β-HSD-12) in subsequent embryogenesis. Taken together, this study proofed that pre-fertilization exposure of abalone eggs, sperm or both to DMP adversely affects the fertilization process and subsequent embryogenesis. PMID:22028799

[Study of a population-wide epidemic outbreak of mumps virus G1 in Jerez de la Frontera (Spain)].

PubMed

González, Pascasio Peña; Barrios, José Almenara; Morales Serna, Juan Carlos

2012-06-01

To characterize the mumps outbreak, assess the effectiveness of vaccines and discuss prevention and control measures. Observational cross-sectional study of cases by person, place, and time. City Jerez de la Frontera and 8 Primary Care centres. A total of 116 cases of mumps were reported throughout seven months, with the last case in June 2008. age, sex, place of study or work, symptoms start date, clinical description, complications, and genotype of virus isolation, history and vaccination compositions. Calculation of total vaccine effectiveness. Active case finding and contact studies were performed on the families, work places and leisure areas. The mean age of the cases was 16.24 years(SD 10.6). The majority (68.96%) of the cases were children at school and 31.03% arose from family and work areas. Mumps vaccine coverage rates were above 90%. The complete vaccine effectiveness (2 doses); for those under 20 years-old it was: 99.84% (95% CI=99.77 - 99.89), being lower in schools with the highest attack rate, immunised with current vaccine from Jeryl Lynn strain: 71.01% (95% CI=55.85 80.97). Two doses of this strain were used in 13.79% of the cases. Susceptible populations were vaccinated at the start of the outbreak: 11,381 doses used in schools and 93 outside schools. An outbreak of mumps virus G 1 population with high rates of mumps vaccine coverage, with areas with low vaccine effectiveness with current vaccine. Mass vaccination of population has contributed to the resolution of the outbreak. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Use of tracheal auscultation for the assessment of bronchial responsiveness in asthmatic children.

PubMed Central

Sprikkelman, A. B.; Grol, M. H.; Lourens, M. S.; Gerritsen, J.; Heymans, H. S.; van Aalderen, W. M.

1996-01-01

BACKGROUND: It can be difficult to assess bronchial responsiveness in children because of their inability to perform spirometric tests reliably. In bronchial challenges lung sounds could be used to detect the required 20% fall in the forced expiratory volume in one second (FEV1). A study was undertaken to determine whether a change in lung sounds corresponded with a 20% fall in FEV1 after methacholine challenge, and whether the occurrence of wheeze was the most important change. METHODS: Fifteen children with asthma (eight boys) of mean age 10.8 years (range 8-15) were studied. All had normal chest auscultation before the methacholine challenge test. Lung sounds were recorded over the trachea for one minute and stored on tape. They were analysed directly and also scored blindly from the tape recording by a second investigator. Wheeze, cough, increase in respiratory rate, and prolonged expiration were assessed. RESULTS: The total cumulative methacholine dose causing a fall in FEV1 of 20% or more (PD20) was detected in 12 children by a change in lung sounds - in four by wheeze and in eight by cough, increased respiratory rate, and/or prolonged expiration. In two subjects altered lung sounds were detectable one dose step before PD20 was reached. In three cases in whom no fall in FEV1 occurred, no change in lung sounds could be detected at the highest methacholine dose. CONCLUSION: Changes in lung sounds correspond well with a 20% fall in FEV1 after methacholine challenge. Wheeze is an insensitive indicator for assessing bronchial responsiveness. Cough, increase in respiratory rate, and prolonged expiration occurs more frequently. PMID:8779140

Equilibrium and kinetic studies of copper biosorption by dead Ceriporia lacerata biomass isolated from the litter of an invasive plant in China.

PubMed

Li, Xiaona; Li, Airong; Long, Mingzhong; Tian, Xingjun

2015-01-01

Ceriporia lacerata, a strain of white-rot fungus isolated from the litter of an invasive plant (Solidago canadensis) in China, was little known about its properties and utilization. In this work, the copper(II) biosorption characteristics of formaldehyde inactivated C. lacerata biomass were examined as a function of initial pH, initial copper(II) concentration and contact time, and the adsorptive equilibrium and kinetics were simulated, too. The optimum pH was found to be 6.0 at experimental conditions of initial copper(II) concentration 100 mg/L, biomass dose 2 g/L, contact time 12 h, shaking rate 150 r/min and temperature 25°C. Biosorption equilibrium cost about 1 hour at experimental conditions of pH 6.0, initial copper(II) concentration 100 mg/L, C. lacerata dose 2 g/L, shaking rate 150 r/min and temperature 25°C. At optimum pH 6.0, highest copper(II) biosorption amounts were 6.79 and 7.76 mg/g for initial copper(II) concentration of 100 and 200 mg/L, respectively (with other experimental parameters of C. lacerata dose 2 g/L, shaking rate 150 r/min and temperature 25°C). The pseudo second-order adsorptive model gave the best adjustment for copper(II) biosorption kinetics. The equilibrium data fitted very well to both Langmuir and Freundlich adsorptive isotherm models. Without further acid or alkali treatment for improving adsorption properties, formaldehyde inactivated C. lacerata biomass possesses good biosorption characteristics on copper(II) removal from aqueous solutions.

Radiation exposure to nuclear medicine staffs during 18F-FDG PET/CT procedures at Ramathibodi Hospital

NASA Astrophysics Data System (ADS)

Donmoon, T.; Chamroonrat, W.; Tuntawiroon, M.

2016-03-01

The aim of this study is to estimate the whole body and finger radiation doses per study received by nuclear medicine staff involved in dispensing, administration of 18F-FDG and interacting with radioactive patients during PET/CT imaging procedures in a PET/CT facility. The whole-body doses received by radiopharmacists, technologists and nurses were measured by electronic dosimeter and the finger doses by ring dosimeter during a period of 4 months. In 70 PET/CT studies, the mean whole-body dose per study to radiopharmacist, technologist, and nurse were 1.07±0.09, 1.77±0.46, μSv, and not detectable respectively. The mean finger doses per study received by radiopharmacist, technologist, and nurse were 265.65±107.55, 4.84±1.08 and 19.22±2.59 μSv, respectively. The average time in contact with 18F-FDG was 5.88±0.03, 39.06±1.89 and 1.21±0.02 minutes per study for radiopharmacist, technologist and nurse respectively. Technologists received highest mean effective whole- body dose per study and radiopharmacist received the highest finger dose per study. When compared with the ICRP dose limit, each individual worker can work with many more 18F- FDG PET/CT studies for a whole year without exceeding the occupational dose limits. This study confirmed that low levels of radiation does are received by our medical personnel involved in 18F-FDG PET/CT procedures.

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients.

PubMed

Lin, Zhixiong; Wang, Xiaoyan; Xie, Wenjia; Yang, Zhining; Che, Kaijun; Wu, Vincent W C

2013-12-01

Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning. © 2013 The Royal Australian and New Zealand College of Radiologists.

Modelling the Ozone-Based Treatments for Inactivation of Microorganisms.

PubMed

Brodowska, Agnieszka Joanna; Nowak, Agnieszka; Kondratiuk-Janyska, Alina; Piątkowski, Marcin; Śmigielski, Krzysztof

2017-10-09

The paper presents the development of a model for ozone treatment in a dynamic bed of different microorganisms ( Bacillus subtilis , B. cereus , B. pumilus , Escherichia coli , Pseudomonas fluorescens , Aspergillus niger , Eupenicillium cinnamopurpureum ) on a heterogeneous matrix (juniper berries, cardamom seeds) initially treated with numerous ozone doses during various contact times was studied. Taking into account various microorganism susceptibility to ozone, it was of great importance to develop a sufficiently effective ozone dose to preserve food products using different strains based on the microbial model. For this purpose, we have chosen the Weibull model to describe the survival curves of different microorganisms. Based on the results of microorganism survival modelling after ozone treatment and considering the least susceptible strains to ozone, we selected the critical ones. Among tested strains, those from genus Bacillus were recognized as the most critical strains. In particular, B. subtilis and B. pumilus possessed the highest resistance to ozone treatment because the time needed to achieve the lowest level of its survival was the longest (up to 17.04 min and 16.89 min for B. pumilus reduction on juniper berry and cardamom seed matrix, respectively). Ozone treatment allow inactivate microorganisms to achieving lower survival rates by ozone dose (20.0 g O₃/m³ O₂, with a flow rate of 0.4 L/min) and contact time (up to 20 min). The results demonstrated that a linear correlation between parameters p and k in Weibull distribution, providing an opportunity to calculate a fitted equation of the process.

Antimalarial activity of the terpene nerolidol.

PubMed

Saito, Alexandre Y; Marin Rodriguez, Adriana A; Menchaca Vega, Danielle S; Sussmann, Rodrigo A C; Kimura, Emília A; Katzin, Alejandro M

2016-12-01

Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Mumps antibody in the Thai population 17 years after the universal measles mumps rubella vaccination program.

PubMed

Ngaovithunvong, Varisara; Wanlapakorn, Nasamon; Tesapirat, Lita; Suratannon, Narrissara; Poovorawan, Yong

2016-08-02

mumps vaccination implementation in the form of MMR - measles, mumps, and rubella) in Thailand for first-grade school students since 1997 and for infants 9-12 months of age since 2010 resulted in a dramatic decline in the incidence of and deaths from mumps. However, there has been a resurgence of mumps outbreaks in Thailand, even in vaccinated populations. We aimed to determine the current seroprevalence of IgG antibodies to mumps in those 0-60 years of age from four different geographic areas of Thailand, and compare the results with our previous serosurvey in 2004. Seropositivity rates in children 0-7 years of age increased significantly from 45.8% in 2004 to 72.3% in 2014 after the launch of the MMR vaccine for infants. In the 8-14-year age group who had received one dose of mumps vaccination, the seropositivity rate was 66.7%. In the 15-19-year age group the seropositivity rate was the lowest, at 52.5%. Our findings correspond well with the vaccination schedules, as the highest seropositivity rate was found in children between 0 and 7 years of age. For those older than 7, there was a decline in seropositivity rate despite good vaccine coverage and reached its lowest in the 15-19-year age group. This suggested that certain population groups might be incompletely vaccinated, or the humoral immunity provided by vaccination gradually declined over time. We recommend a booster dose of MMR vaccine for Thai adolescents in order to prevent future mumps outbreaks.

Efficiency of combined process of ozone and bio-filtration in the treatment of secondary effluent.

PubMed

Tripathi, Smriti; Tripathi, B D

2011-07-01

The present work was aimed at studying the efficiency of the combined process of biofiltration with ozonation to improve the quality of secondary effluent. The secondary effluent from the Dinapur Sewage Treatment Plant Varanasi, India was used in this work. The process of biofiltration with the plant species of Eichornia crassipes and Lemna minor, at a flow rate of 262 ml min(-1) and plant density of 30 mg L(-1) for 48 h, in combination with the process of ozonation with ozone dose of 10 mg L(-1) and contact time of 5 min was applied. Results revealed that combined process was statistically most suitable for the highest degradation of physico-chemical and microbial parameters with improving BDOC value. The biofiltration process is able to remove highest percentage of toxic heavy metals from the secondary effluent without production of toxicity. This technique is highly recommendable for tropical wastewater where sewage is mixed with industrial effluents. Copyright © 2011 Elsevier Ltd. All rights reserved.

Isolation of prolyl endopeptidase inhibitory peptides from a sodium caseinate hydrolysate.

PubMed

Hsieh, Cheng-Hong; Wang, Tzu-Yuan; Hung, Chuan-Chuan; Hsieh, You-Liang; Hsu, Kuo-Chiang

2016-01-01

Prolyl endopeptidase (PEP) has been associated with neurodegenerative disorders, and the PEP inhibitors can restore the memory loss caused by amnesic compounds. In this study, we investigated the PEP inhibitory activity of the enzymatic hydrolysates from various food protein sources, and isolated and identified the PEP inhibitory peptides. The hydrolysate obtained from sodium caseinate using bromelain (SC/BML) displayed the highest inhibitory activity of 86.8% at 5 mg mL(-1) in the present study, and its IC50 value against PEP was 0.77 mg mL(-1). The F-5 fraction by RP-HPLC (reversed-phase high performance liquid chromatography) from SC/BML showed the highest PEP inhibition rate of 88.4%, and 9 peptide sequences were identified. The synthetic peptides (1245.63-1787.94 Da) showed dose-dependent inhibition effects on PEP as competitive inhibitors with IC50 values between 29.8 and 650.5 μM. The results suggest that the peptides derived from sodium caseinate have the potential to be PEP inhibitors.

β1 -Adrenoceptor, but not β2 -adrenoceptor, subtype regulates heart rate in type 2 diabetic rats in vivo.

PubMed

Cook, Rosalind F; Bussey, Carol T; Mellor, Kimberley M; Cragg, Patricia A; Lamberts, Regis R

2017-08-01

What is the central question of the study? The sympathetic system regulates heart rate via β-adrenoceptors; this is impaired during diabetes. However, the specific β-adrenoceptor subtype contributions in heart rate regulation in diabetes in vivo are unknown. What is the main finding and its importance? Telemetric recordings in conscious non-diabetic and type 2 diabetic rats demonstrated that the β 1 -adrenoceptor subtype, and not the β 2 -adrenoceptor, regulated the lower resting heart rate and increased β-adrenoceptor responsiveness in diabetes in vivo. This provides new physiological insight into the dysregulation of heart rate in type 2 diabetes, which is important for improving therapeutic strategies targeting the diabetic chronotropic incompetence. β-Adrenoceptor blockers are widely used to reduce heart rate, the strongest predictor of mortality in cardiac patients, but are less effective in diabetic patients. This study aimed to determine the specific contributions of β 1 - and β 2 -adrenoceptor subtypes to chronotropic responses in type 2 diabetes in vivo, which are currently unknown. Type 2 diabetic and non-diabetic rats were implanted with radiotelemeters to measure arterial blood pressure and derive heart rate in conscious conditions. Vascular access ports were implanted to inject isoprenaline (β 1 - and β 2 -adrenoceptor agonist, 0.1-300 μg kg -1 ) in the presence of atenolol (β 1 -adrenoceptor antagonist, 2000 μg kg -1 ) or nadolol (β 1 - and β 2 -adrenoceptor agonist, 4000 μg kg -1 ) to determine the chronotropic contributions of the β-adrenoceptor subtypes. Resting heart rate was reduced in diabetic rats (388 ± 62 versus 290 ± 37 beats min -1 non-diabetic versus diabetic, P < 0.05, mean ± SD), which remained after atenolol or nadolol administration. Overall β-adrenoceptor chronotropic responsiveness was increased in diabetic rats (change in heart rate at highest dose of isoprenaline: 135 ± 66 versus 205 ± 28 beats min -1 , non-diabetic versus diabetic, P < 0.05), a difference that diminished after β 1 -adrenoceptor blockade with atenolol (change in heart rate at highest dose of isoprenaline: 205 ± 37 versus 195 ± 22 beats min -1 , non-diabetic versus diabetic, P < 0.05). In conclusion, the β 1 -adrenoceptor is the main subtype to modulate chronotropic β-adrenoceptor responses in healthy and diabetic rats. This study provides new insights into the pathological basis of dysregulation of heart rate in type 2 diabetes, which could be important for improving the current therapeutic strategies targeting diabetic chronotropic incompetence. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

ELDRS Characterization for a Very High Dose Mission

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

PubMed

Palmsten, Kristin; Rolland, Matthieu; Hebert, Mary F; Clowse, Megan E B; Schatz, Michael; Xu, Ronghui; Chambers, Christina D

2018-04-01

To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose. Copyright © 2018 John Wiley & Sons, Ltd.

Dose rate effects in the radiation damage of the plastic scintillators of the CMS hadron endcap calorimeter

DOE PAGES

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

2016-10-07

We present measurements of the reduction of light output by plastic scintillators irradiated in the CMS detector during the 8 TeV run of the Large Hadron Collider and show that they indicate a strong dose rate effect. The damage for a given dose is larger for lower dose rate exposures. The results agree with previous measurements of dose rate effects, but are stronger due to the very low dose rates probed. Here, we show that the scaling with dose rate is consistent with that expected from diffusion effects.

Skipjack tuna (Katsuwonus pelamis) eyeball oil exerts an anti-inflammatory effect by inhibiting NF-κB and MAPK activation in LPS-induced RAW 264.7 cells and croton oil-treated mice.

PubMed

Jeong, Da-Hyun; Kim, Koth-Bong-Woo-Ri; Kim, Min-Ji; Kang, Bo-Kyeong; Ahn, Dong-Hyun

2016-11-01

The effect of tuna eyeball oil (TEO) on lipopolysaccharide (LPS)-induced inflammation in macrophage cells was investigated. TEO had no cytotoxicity in cell viability as compared to the control in LPS induced RAW 264.7 cells. TEO reduced the levels of NO and pro-inflammatory cytokines by up to 50% in a dose-dependent manner. The expression of NF-κB and MAPKs as well as iNOS and COX-2 proteins was reduced by TEO, which suggests that its anti-inflammatory activity is related to the suppression of the NF-κB and MAPK signaling pathways. The rate of formation of ear edema was reduced compared to that in the control at the highest dose tested. In an acute toxicity test, no mice were killed by TEO doses of up to 5000mg/kg body weight during the two week observation period. These results suggested that TEO may have a significant effect on inflammatory factors and be a potential anti-inflammatory therapeutic. Copyright © 2016 Elsevier B.V. All rights reserved.

Space Weather at Mars: MAVEN and MSL/RAD Observations of CME and SEP Events

NASA Astrophysics Data System (ADS)

Lee, C. O.; Ehresmann, B.; Lillis, R. J.; Dunn, P.; Rahmati, A.; Larson, D. E.; Guo, J.; Zeitlin, C.; Luhmann, J. G.; Halekas, J. S.; Espley, J. R.; Thiemann, E.; Hassler, D.

2017-12-01

While MAVEN have been observing the space weather conditions driven by ICMEs and SEPs in orbit around Mars, MSL/RAD have been measuring the surface radiation environment due to E > 150 MeV/nuc SEPs and the higher-energy galactic cosmic rays. The suite of MAVEN instruments measuring the particles (SEP), plasma (SWIA) and fields (MAG) information provides detailed local space weather information regarding the solar activity-related fluctuations in the measured surface dose rates. At the same time, the related enhancements in the RAD surface dose rates indicate the degree to which the SEPs affect the lower atmosphere and surface. We will present an overview of the MAVEN observations together with the MSL/RAD measurements and focus our discussion on a number of space weather events driven by CMEs and SEPs. During the March 2015 solar storm period, a succession of CMEs produced intense SEP proton fluxes that were detected by MAVEN/SEP in the 20 keV to 6 MeV detected energy channels. At higher energies, MAVEN/SEP record `FTO' SEP events that were triggered by > 13 MeV energetic protons passing through all three silicon detector layers (Front, Thick, and Open). Using the detector response matrix for an FTO event (incident energy vs detected energy), the minimum incident energy of the SEP protons observed in March 2015 was inferred to be > 40 MeV. The lack of any notable enhancements in the surface dose rate by MSL/RAD suggests that the highest incident energies of the SEP protons were < 150 MeV. Note that Forbush-like decreases were observed due to the local passages of the ICMEs. In contrast, MSL/RAD detected dose rate enhancements above the background level in October 2015 even though the MAVEN SWIA and MAG instruments did not detect any local passage of an ICME nor did the SEP instrument observe any SEP proton fluxes in the 20 keV to 6 MeV energy channels. However, MAVEN/SEP did record an FTO event that coincided with the RAD dose rate enhancement, all of which suggest that > 150 MeV SEP protons impacted the Martian atmosphere and surface. The source of the October 2015 SEP event was probably the CME that erupted near the solar west limb with respect to the Sun-Mars line. As part of the discussion, we will also show solar-heliospheric observations from near-Earth assets together with WSA-Enlil-cone results for some global heliospheric context.

Dose-finding trial of a combined regimen with bevacizumab, immunotherapy, and chemotherapy in patients with metastatic renal cell cancer: An Italian Oncology Group for Clinical Research (GOIRC) study.

PubMed

Buti, Sebastiano; Lazzarelli, Silvia; Chiesa, Matteo Dalla; Simonelli, Cecilia; Re, Giovanni Lo; Lheshi, Arvin; Simon, Spazzapan; Mattioli, Rodolfo; Caminiti, Caterina; Mazza, Giancarlo; Donini, Maddalena; Passalacqua, Rodolfo

2010-09-01

The aim of this study was to look for the maximum tolerated dose (MTD) of gemcitabine and 5-fluorouracil in a new regimen also containing the antiangiogenic bevacizumab and immunotherapy (IT) for the treatment of metastatic renal cell cancer. The primary objective of this multicenter dose-finding study was to establish the MTD of chemotherapy (CT) in combination with fixed doses of IT and bevacizumab. The secondary objective was to assess the combination's activity. Five escalated dose levels of CT with intravenous gemcitabine and 5-fluorouracil (days 1 and 8 every 28 d), were associated together with intravenous bevacizumab (10 mg/kg on days 1 and 15 every 28 d), subcutaneous interleukin-2 (1 MIU/m² bid on days 8, 9, 15, 16, and 1 MIU/m²/d on days 10-12 and 17-19), and interferon-α-2a (3 MIU on days 10, 12, 17, 19). Of the 27 enrolled patients, 59% had been pretreated. The MTD was not reached. The highest CT dose studied was gemcitabine 1000 mg/m² and 5-fluorouracil 600 mg/m². More frequent grade 3 to 4 toxicities included neutropenia (63%), thrombocytopenia (33%), and fever (26%). The response rate was 33% according to the Response Evaluation Criteria in Solid Tumors. This is the first study that explored the feasibility and safety of combined bevacizumab, IT, and CT in metastatic renal cell cancer. The activity of this regimen is interesting and its efficacy warrants further trials.

Phase I-II Study of Intraoperative Radiation Therapy (IORT) After Radical Prostatectomy for Prostate Cancer

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

Saracino, Biancamaria; Gallucci, Michele; De Carli, Piero

2008-07-15

Purpose: Recent studies have suggested an {alpha}/{beta} ratio in prostate cancer of 1.5-3 Gy, which is lower than that assumed for late-responsive normal tissues. Therefore the administration of a single, intraoperative dose of irradiation should represent a convenient irradiation modality in prostate cancer. Materials and Methods: Between February 2002 and June 2004, 34 patients with localized prostate cancer with only one risk factor (Gleason score {>=}7, Clinical Stage [cT] {>=}2c, or prostate-specific antigen [PSA] of 11-20 ng/mL) and without clinical evidence of lymph node metastases were treated with radical prostatectomy (RP) and intraoperative radiotherapy on the tumor bed. A dose-findingmore » procedure based on the Fibonacci method was employed. Dose levels of 16, 18, and 20 Gy were selected, which are biologically equivalent to total doses of about 60-80 Gy administered with conventional fractionation, using an {alpha}/{beta} ratio value of 3. Results: At a median follow-up of 41 months, 24 (71%) patients were alive with an undetectable PSA value. No patients died from disease, whereas 2 patients died from other malignancies. Locoregional failures were detected in 3 (9%) patients, 2 in the prostate bed and 1 in the common iliac node chain outside the radiation field. A PSA rise without local or distant disease was observed in 7 (21%) cases. The overall 3-year biochemical progression-free survival rate was 77.3%. Conclusions: Our dose-finding study demonstrated the feasibility of intraoperative radiotherapy in prostate cancer also at the highest administered dose.« less

Embryotoxicity of orally administered chromium in mice: exposure during the period of organogenesis.

PubMed

Junaid, M; Murthy, R C; Saxena, D K

1996-03-01

Administration of chromium (VI)(250, 500 and 750 ppm as potassium dichromate) via drinking water during organogenesis (days 6-14 of gestation) in mice revealed embryo- and fetotoxic effects. Reduced fetal weight, retarded fetal development, number of fetuses (live and dead) per mother and high incidences of dead fetuses and resorptions in treated mothers in the highest dosed group were evident. No significant gross structural abnormalities were observed in any of the fetuses of chromium (VI)-treated mothers. Significant incidences of reduced ossification were found in the highest dosed group. Chromium levels were increased in a dose-dependent manner in maternal blood, placenta and fetuses. The present study suggests a risk to the developing embryo if the mother is exposed to a sufficiently high concentration of chromium (VI) through drinking water during the period of organogenesis.

Radiolead (210)Pb and (210)Po/(210)Pb activity ratios in calcium supplements and the assessment of their possible dose to consumers.

PubMed

Strumińska-Parulska, Dagmara I

2016-08-23

This paper presents the results of pioneer study of the most popular calcium supplements as a potential additional source of radiolead (210)Pb in human diet. The analyzed calcium pharmaceutics contained organic or inorganic calcium compounds; some came from natural sources as mussels' shells, fish extracts, or sedimentary rocks. The idea was to investigate the naturally occurring (210)Pb activity in different calcium supplements and calculate the annual effective radiation dose from radiolead (210)Pb decay in consumed calcium supplement. The results showed (210)Pb concentrations in natural origin calcium supplements (especially sedimentary rocks) were significantly higher. The highest (210)Pb activity concentrations were determined in mineral tablets made from dolomite - 2.97 ± 0.18 mBq g(-1), while the lowest was observed in organic calcium compounds - both calcium lactate - 0.08 ± 0.01 and 0.13 ± 0.01 mBq g(-1). The highest annual radiation dose from (210)Pb taken with 1 tablet of calcium supplement per day was calculated for soluble calcium lactate sample - 1.19 ± 0.03 µSv year(-1), while the highest annual radiation dose from (210)Pb taken daily with 1 g of pure Ca for dolomite - 5.57 ± 0.34 µSv year(-1).

Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.

PubMed

Kotronoulas, Aristotelis; Pizarro, Nieves; Serra, Aida; Robledo, Patricia; Joglar, Jesús; Rubió, Laura; Hernaéz, Alvaro; Tormos, Carmen; Motilva, Ma José; Fitó, Montserrat; Covas, Maria-Isabel; Solà, Rosa; Farré, Magí; Saez, Guillermo; de la Torre, Rafael

2013-11-01

Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested. Copyright © 2013. Published by Elsevier Ltd.

Upper-Bound Radiation Dose Assessment for Military Personnel at McMurdo Station, Antarctica, between 1962 and 1979, Revision 1

DTIC Science & Technology

2016-07-29

using Equation 2 (DTRA, 2010, ED01): Dmonitor highest average HT TLD D = (2) where: TLDhighest = Highest TLD measurement during environmental...the processing of administrative claims or litigation. For use by Agency officials, employees, and authorized contractors . ROUTINE USES

The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

PubMed Central

Brooks, Antone L.; Hoel, David G.; Preston, R. Julian

2016-01-01

Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006). PMID:27266588

Application of a computational decision model to examine acute drug effects on human risk taking.

PubMed

Lane, Scott D; Yechiam, Eldad; Busemeyer, Jerome R

2006-05-01

In 3 previous experiments, high doses of alcohol, marijuana, and alprazolam acutely increased risky decision making by adult humans in a 2-choice (risky vs. nonrisky) laboratory task. In this study, a computational modeling analysis known as the expectancy valence model (J. R. Busemeyer & J. C. Stout, 2002) was applied to individual-participant data from these studies, for the highest administered dose of all 3 drugs and corresponding placebo doses, to determine changes in decision-making processes that may be uniquely engendered by each drug. The model includes 3 parameters: responsiveness to rewards and losses (valence or motivation); the rate of updating expectancies about the value of risky alternatives (learning/memory); and the consistency with which trial-by-trial choices match expected outcomes (sensitivity). Parameter estimates revealed 3 key outcomes: Alcohol increased responsiveness to risky rewards and decreased responsiveness to risky losses (motivation) but did not alter expectancy updating (learning/memory); both marijuana and alprazolam produced increases in risk taking that were related to learning/memory but not motivation; and alcohol and marijuana (but not alprazolam) produced more random response patterns that were less consistently related to expected outcomes on the 2 choices. No significant main effects of gender or dose by gender interactions were obtained, but 2 dose by gender interactions approached significance. These outcomes underscore the utility of using a computational modeling approach to deconstruct decision-making processes and thus better understand drug effects on risky decision making in humans.

Predictors of Infant Hepatitis B Immunization in Cameroon: Data to Inform Implementation of a Hepatitis B Birth Dose.

PubMed

Dionne-Odom, Jodie; Westfall, Andrew O; Nzuobontane, Divine; Vinikoor, Michael J; Halle-Ekane, Gregory; Welty, Thomas; Tita, Alan T N

2018-01-01

Although most African countries offer hepatitis B immunization through a 3-dose vaccine series recommended at 6, 10 and 14 weeks of age, very few provide birth dose vaccination. In support of Cameroon's national plan to implement the birth dose vaccine in 2017, we investigated predictors of infant hepatitis B virus (HBV) vaccination under the current program. Using the 2011 Demographic Health Survey in Cameroon, we identified women with at least one living child (age 12-60 months) and information about the hepatitis B vaccine series. Vaccination rates were calculated, and logistic regression modeling was used to identify factors associated with 3-dose series completion. Changes over time were assessed with linear logistic model. Among 4594 mothers analyzed, 66.7% (95% confidence interval [CI]: 64.1-69.3) of infants completed the hepatitis B vaccine series; however, an average 4-week delay in series initiation was noted with median dose timing at 10, 14 and 19 weeks of age. Predictors of series completion included facility delivery (adjusted odds ratio [aOR]: 2.1; 95% CI: 1.7-2.6), household wealth (aOR: 1.9; 95% CI: 1.2-3.1 comparing the highest and lowest quintiles), Christian religion (aOR: 1.8; 95% CI: 1.3-2.5 compared with Muslim religion) and older maternal age (aOR: 1.4; 95% CI: 1.2-1.7 for 10 year units). Birth dose vaccination to reduce vertical and early childhood transmission of hepatitis B may overcome some of the obstacles to timely and complete HBV immunization in Cameroon. Increased awareness of HBV is needed among pregnant women and high-risk groups about vertical transmission, the importance of facility delivery and the effectiveness of prevention beginning with monovalent HBV vaccination at birth.

Nonclinical Safety and Toxicokinetics of MnTnBuOE-2-PyP5+ (BMX-001).

PubMed

Gad, Shayne Cox; Sullivan, Dexter W; Spasojevic, Ivan; Mujer, Cesar V; Spainhour, Charles B; Crapo, James D

2016-07-01

BMX-001, a manganese porphyrin that has anti-inflammatory, antioxidant, and antitumor properties, is being developed as a potential therapeutic for high-grade glioma (HGG) and head and neck (H&N) cancer. An IND has been opened for BMX-001 in the treatment of HGG (NCT02655601) and another is in preparation for H&N. The safety of BMX-001 has been evaluated in a battery of nonclinical Good Laboratory Practice (GLP)-compliant studies. Systemic toxicity has been evaluated using the intended cGMP product administered subcutaneously for periods of up to 5 weeks in both the mouse and the monkey and included toxicokinetic evaluations to characterize systemic exposure and tissue distribution and clearance of BMX-001. In additional GLP studies, BMX-001 was not irritating to the skin or eye and caused no changes in cardiac rate or rhythm or blood pressure. Mixed results for genotoxicity were seen with the weight of evidence indicating that BMX-001 poses no genotoxic risk in humans. In systemic mouse and monkey studies, loading/maintenance dose no observed adverse effect levels were 12/2 mg/kg/dose and 6/2 mg/kg/dose, respectively, with maintenance doses administered every 3 days after the initial loading dose. Systemic data were used to determine a Food and Drug Administration-approved safe starting dose for the initial clinical study in patients with HGG. BMX-001 was detected in analyzed tissues, including the brain, persisting well past the short plasma clearance period. The highest levels of BMX-001 were seen in the liver and kidneys, with amounts in these tissues returning to close to undetectable levels after a 2-week cessation of dosing. © The Author(s) 2016.

A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer.

PubMed

Liu, Joyce F; Tolaney, Sara M; Birrer, Michael; Fleming, Gini F; Buss, Mary K; Dahlberg, Suzanne E; Lee, Hang; Whalen, Christin; Tyburski, Karin; Winer, Eric; Ivy, Percy; Matulonis, Ursula A

2013-09-01

Poly(ADP-ribose) polymerase (PARP)-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3 and olaparib, a PARP-inhibitor (NCT01116648). Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or met Gynecologic Cancer InterGroup (GCIG) CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia ≥ 4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD) > 24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for > 24 weeks. The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

SU-F-T-304: Complex Multi-PTV Treatment Evaluation Using a Remotely Processed 3D Gel Dosimeter

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

Hoisak, J; Dragojevic, I; Sutlief, S

Purpose: A new 3D gel dosimeter (ClearView™, Modus Medical Systems) was investigated for use as a QA tool for stereotactic radiosurgery (SRS) plans exhibiting high dose gradients and spatially separated treatment targets. The unique feature of this gel dosimeter is the remote processing service provided by Modus Medical Systems. Methods: The gel dosimeters were filled in either 10 cm diameter or 15 cm diameter clear plastic jars. The jars were then shipped in ice-cooled containers to our department for irradiation. Clinical SRS plans for treatment of multiple metastases and plans with simulated concave structures were applied to a CT scanmore » of the gel dosimeter. The gel was irradiated in treatment position using modulated arcs and then returned in the cooled container for processing. The 3D gel dose was compared to the DICOM-RT dose from the treatment plan to assess dosimetric and geometric agreement. Results: There was no discernible difference between the planned and measured dose for dose gradients as high as 10%/mm, which was the highest gradient we evaluated. Geometric agreement for distant metastases separated by 6 cm was within 1.5 mm. Among three identically irradiated gels using a plan intended for nine metastases, the 3%/3mm gamma passing rate was 84.5% with a range of 14.7%, measured over the entire volume of the dosimeter. Regions of larger gamma values correlated with geometric offsets between the planned and measured data. Conclusion: The gel dosimeter exhibits the dosimetric and geometric characteristics necessary for 3D evaluation of treatment plan deliverability. The range of observed gamma passing rates suggests a high sensitivity to geometric registration. With proper management of geometric registration between planned and measured data, this service should enable a radiation oncology department to use 3D dosimetry in end-to-end testing or patient plan delivery QA without the expense of an in-house processing system.« less

Preconception Low-Dose Aspirin Restores Diminished Pregnancy and Live Birth Rates in Women With Low-Grade Inflammation: A Secondary Analysis of a Randomized Trial.

PubMed

Sjaarda, Lindsey A; Radin, Rose G; Silver, Robert M; Mitchell, Emily; Mumford, Sunni L; Wilcox, Brian; Galai, Noya; Perkins, Neil J; Wactawski-Wende, Jean; Stanford, Joseph B; Schisterman, Enrique F

2017-05-01

Inflammation is linked to causes of infertility. Low-dose aspirin (LDA) may improve reproductive success in women with chronic, low-grade inflammation. To investigate the effect of preconception-initiated LDA on pregnancy rate, pregnancy loss, live birth rate, and inflammation during pregnancy. Stratified secondary analysis of a multicenter, block-randomized, double-blind, placebo-controlled trial. Four US academic medical centers, 2007 to 2012. Healthy women aged 18 to 40 years (N = 1228) with one to two prior pregnancy losses actively attempting to conceive. Preconception-initiated, daily LDA (81 mg) or matching placebo taken up to six menstrual cycles attempting pregnancy and through 36 weeks' gestation in women who conceived. Confirmed pregnancy, live birth, and pregnancy loss were compared between LDA and placebo, stratified by tertile of preconception, preintervention serum high-sensitivity C-reactive protein (hsCRP) (low, <0.70 mg/L; middle, 0.70 to <1.95 mg/L; high, ≥1.95 mg/L). Live birth occurred in 55% of women overall. The lowest pregnancy and live birth rates occurred among the highest hsCRP tertile receiving placebo (44% live birth). LDA increased live birth among high-hsCRP women to 59% (relative risk, 1.35; 95% confidence interval, 1.08 to 1.67), similar to rates in the lower and mid-CRP tertiles. LDA did not affect clinical pregnancy or live birth in the low (live birth: 59% LDA, 54% placebo) or midlevel hsCRP tertiles (live birth: 59% LDA, 59% placebo). In women attempting conception with elevated hsCRP and prior pregnancy loss, LDA may increase clinical pregnancy and live birth rates compared with women without inflammation and reduce hsCRP elevation during pregnancy. Copyright © 2017 by the Endocrine Society

Radiation and Plasma Environments for Lunar Missions

NASA Technical Reports Server (NTRS)

Minow, Joseph I.; Edwards, David L.; Altstatt, Richard L.; Diekmann, Anne M.; Blackwell, William C., Jr.; Harine, Katherine J.

2006-01-01

Space system design for lunar orbit and extended operations on the lunar surface requires analysis of potential system vulnerabilities to plasma and radiation environments to minimize anomalies and assure that environmental failures do not occur during the mission. Individual environments include the trapped particles in Earth s radiation belts, solar energetic particles and galactic cosmic rays, plasma environments encountered in transit to the moon and on the lunar surface (solar wind, terrestrial magnetosheath and magnetotail, and lunar photoelectrons), and solar ultraviolet and extreme ultraviolet photons. These are the plasma and radiation environments which contribute to a variety of effects on space systems including total ionizing dose and dose rate effects in electronics, degradation of materials in the space environment, and charging of spacecraft and lunar dust. This paper provides a survey of the relevant charged particle and photon environments of importance to lunar mission design ranging from the lowest (approx.few 10 s eV) photoelectron energies to the highest (approx.GeV) cosmic ray energies.

Percutaneous toxicity and decontamination of soman, VX, and paraoxon in rats using detergents.

PubMed

Misík, Jan; Pavliková, Růžena; Kuča, Kamil

2013-06-01

Highly toxic organophosphorus compounds (OPs) were originally developed for warfare or as agricultural pesticides. Today, OPs represent a serious threat to military personnel and civilians. This study investigates the in vivo decontamination of male Wistar rats percutaneously exposed to paraoxon and two potent nerve agents--soman (GD) and VX. Four commercial detergents were tested as decontaminants--Neodekont(TM), Argos(TM), Dermogel(TM), and FloraFree(TM). Decontamination performed 2 min after exposure resulted in a higher survival rate in comparison with non-decontaminated controls. The decontamination effectiveness was expressed as protective ratio (PR, median lethal dose of agent in decontaminated animals divided by the median lethal dose of agent in untreated animals). The highest decontamination effectiveness was consistently achieved with Argos(TM) (PR=2.3 to 64.8), followed by Dermogel(TM) (PR=2.4 to 46.1). Neodekont(TM) and FloraFree(TM) provided the lowest decontamination effectiveness, equivalent to distilled water (PR=1.0 to 43.2).

Radiation dose-rate meter using an energy-sensitive counter

DOEpatents

Kopp, Manfred K.

1988-01-01

A radiation dose-rate meter is provided which uses an energy-sensitive detector and combines charge quantization and pulse-rate measurement to monitor radiation dose rates. The charge from each detected photon is quantized by level-sensitive comparators so that the resulting total output pulse rate is proportional to the dose-rate.

Radiation exposure to the eye lens of orthopaedic surgeons during various orthopaedic procedures.

PubMed

Romanova, K; Vassileva, J; Alyakov, M

2015-07-01

The aim of the present study was to assess the radiation dose to the eye lens of orthopaedic surgeons during various orthopaedic procedures and to make efforts to ensure that radiation protection is optimised. The study was performed for Fractura femoris and Fractura cruris procedures performed in orthopaedic operating theatres, as well as for fractures of wrist, ankle and hand/shoulder performed in the emergency trauma room. The highest mean value of the eye lens dose of 47.2 μSv and higher mean fluoroscopy time of 3 min, as well as the corresponding highest maximum values of 77.1 μSv and 5.0 min were observed for the Fractura femoris procedure performed with the Biplanar 500e fluoroscopy systems. At a normal workload, the estimated mean annual dose values do not exceed the annual occupational dose limit for the lens of eye, but at a heavy workload in the department, this dose limit could be achieved or exceeded. The use of protective lead glasses is recommended as they could reduce the radiation exposure of the lens of the eye. The phantom measurements demonstrated that the use of half-dose mode could additionally reduce dose to the operator's eye lens. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Preclinical toxicity profile of oral bilastine.

PubMed

Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

2012-06-01

As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

Occupational and diagnostic exposure to ionizing radiation and leukemia risk among German uranium miners.

PubMed

Möhner, Matthias; Gellissen, Johannes; Marsh, James W; Gregoratto, Demetrio

2010-09-01

Lung cancer is a well-known effect of radon exposure in uranium mines. However, little is known about the induction of leukemia by radiation exposure in mines. Moreover, miners usually have occupational medical checkup programs that include chest x-ray examinations. Therefore, the aim of the present study was to re-examine leukemia risk among miners, taking into account exposure to x rays for diagnostic purposes. The data used were from a previously analyzed individually matched case-control study of former uranium miners in East Germany with 377 cases and 980 controls. Additionally, data on x-ray examinations were taken from medical records for most of the subjects. Finally, the absorbed dose to red bone marrow was calculated considering both occupational and diagnostic exposures. Using conditional logistic regression models, a moderately but not statistically significant elevated risk was seen in the dose category above 200 mGy for the combined dose from both sources [odds ratio (OR) = 1.33, 90% confidence interval (CI): (0.82-2.14)]. Ignoring the dose accumulated in the recent 20 y, the risk in the highest dose category (>105 mGy) was higher [OR = 1.77, 90% CI: (1.06-2.95)]. Ignoring diagnostic exposure yielded similar results. For the highest dose category (absorbed dose lagged by 20 y) the risk was more than doubled [OR = 2.64, 90% CI: (1.60-4.35)].

Pediatric Phantom Dosimetry of Kodak 9000 Cone-beam Computed Tomography.

PubMed

Yepes, Juan F; Booe, Megan R; Sanders, Brian J; Jones, James E; Ehrlich, Ygal; Ludlow, John B; Johnson, Brandon

2017-05-15

The purpose of the study was to evaluate the radiation dose of the Kodak 9000 cone-beam computed tomography (CBCT) device for different anatomical areas using a pediatric phantom. Absorbed doses resulting from maxillary and mandibular region three by five cm CBCT volumes of an anthropomorphic 10-year-old child phantom were acquired using optical stimulated dosimetry. Equivalent doses were calculated for radiosensitive tissues in the head and neck area, and effective dose for maxillary and mandibular examinations were calculated following the 2007 recommendations of the International Commission on Radiological Protection (ICRP). Of the mandibular scans, the salivary glands had the highest equivalent dose (1,598 microsieverts [μSv]), followed by oral mucosa (1,263 μSv), extrathoracic airway (pharynx, larynx, and trachea; 859 μSv), and thyroid gland (578 μSv). For the maxilla, the salivary glands had the highest equivalent dose (1,847 μSv), followed closely by oral mucosa (1,673 μSv), followed by the extrathoracic airway (pharynx, larynx, and trachea; 1,011 μSv) and lens of the eye (202 μSv). Compared to previous research of the Kodak 9000, completed with the adult phantom, a child receives one to three times more radiation for mandibular scans and two to 10 times more radiation for maxillary scans.

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Do we need 3D tube current modulation information for accurate organ dosimetry in chest CT? Protocols dose comparisons.

PubMed

Lopez-Rendon, Xochitl; Zhang, Guozhi; Coudyzer, Walter; Develter, Wim; Bosmans, Hilde; Zanca, Federica

2017-11-01

To compare the lung and breast dose associated with three chest protocols: standard, organ-based tube current modulation (OBTCM) and fast-speed scanning; and to estimate the error associated with organ dose when modelling the longitudinal (z-) TCM versus the 3D-TCM in Monte Carlo simulations (MC) for these three protocols. Five adult and three paediatric cadavers with different BMI were scanned. The CTDI vol of the OBTCM and the fast-speed protocols were matched to the patient-specific CTDI vol of the standard protocol. Lung and breast doses were estimated using MC with both z- and 3D-TCM simulated and compared between protocols. The fast-speed scanning protocol delivered the highest doses. A slight reduction for breast dose (up to 5.1%) was observed for two of the three female cadavers with the OBTCM in comparison to the standard. For both adult and paediatric, the implementation of the z-TCM data only for organ dose estimation resulted in 10.0% accuracy for the standard and fast-speed protocols, while relative dose differences were up to 15.3% for the OBTCM protocol. At identical CTDI vol values, the standard protocol delivered the lowest overall doses. Only for the OBTCM protocol is the 3D-TCM needed if an accurate (<10.0%) organ dosimetry is desired. • The z-TCM information is sufficient for accurate dosimetry for standard protocols. • The z-TCM information is sufficient for accurate dosimetry for fast-speed scanning protocols. • For organ-based TCM schemes, the 3D-TCM information is necessary for accurate dosimetry. • At identical CTDI vol , the fast-speed scanning protocol delivered the highest doses. • Lung dose was higher in XCare than standard protocol at identical CTDI vol .

Estimated ultraviolet radiation doses in wetlands in six national parks

USGS Publications Warehouse

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

2005-01-01

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

Monochromatic Spectral Computed Tomography with Low Iodine Concentration Contrast Medium in a Rabbit VX2 Liver Model:: Investigation of Image Quality and Detection Rate.

PubMed

Zhou, Yue; Xu, Han; Hou, Ping; Dong, Jun Q; Wang, Ming Y; Gao, Jian B

2016-04-01

This study aimed to validate the feasibility of using virtual monochromatic spectral computed tomography (CT) with isotonic low iodine concentration contrast medium for VX2 hepatic tumors. Sixty New Zealand white rabbits with implanted VX2 hepatic tumors underwent two-phase contrast-enhanced spectral CT imaging on the 14th day after tumor implantation. They were randomly divided into groups A, B, and C, with 20 rabbits each (group A: 270 mg I/mL, monochromatic spectral images; group B: 370 mg I/mL, conventional 120 kVp images, 100% filtered back projection [FBP]; group C: 270 mg I/mL, conventional 120 kVp images, 100% FBP). Group A was further divided into two subgroups (subgroup A1: 100% FBP; subgroup A2: 50% FBP + 50% adaptive statistical iterative reconstruction). Objective evaluation (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and image noise), subjective rating score (image noise score, anatomical details score, overall image quality score, and lesion conspicuity score), CT dose index volume, and dose length product were compared between groups during two-phase contrast enhancement. The detection rates of the four groups were calculated as percentages. Image noise (SNR and CNR) among the four groups was statistically significant (P <0.05). The image noise in group A2 was lower than in group A1, but higher than that in groups B and C (P <0.05). SNR and CNR in group A2 were the highest, followed by group A1, and group C was the lowest (P <0.05 for all). The image noise score of group A2 was higher than that of the other three groups. In terms of the anatomic details score, the overall image quality score, and the lesion conspicuity score, the images of group A2 were superior to that of groups A1 and C. For hepatic tumor diameters more than or equal to 1.0 cm and less than 3.0 cm, group A achieved a higher detection rate than groups B and C. The CT dose index volume, dose length product, and effective dose in group A were significantly lower than that in groups B and C (P <0.05). On average, group A reduced the effective radiation dose by 27.2% compared to group B, whereas group B reduced the effective radiation dose by 28% compared to group C. Group A reduced the iodine load by 22.86% compared to group B. The use of monochromatic images combined with 50% adaptive statistical iterative reconstruction with an isotonic low concentration contrast medium of 270 mg I/mL can optimize image quality, reduce image noise, increase detection rate for small tumors, and decrease radiation dose and iodine load in hepatic tumor CT examinations. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Advanced treatment of biotreated textile industry wastewater with ozone, virgin/ozonated granular activated carbon and their combination.

PubMed

Arslan-Alaton, Idil; Seremet, Ozden

2004-01-01

Biotreated textile wastewater (CODo = 248 mg L(-1); TOCo = 58 mg L(-1); A620 = 0.007 cm(-1); A525 = 0.181 cm(-1); A436 = 0.198 cm(-1)) was subjected to advanced treatment with ozonation, granular activated carbon (GAC) adsorption in serial and simultaneous applications. Experiments were conducted to investigate the effects of applied ozone dose, ozone absorption rate, specific ozone absorption efficiency, GAC dose, and reaction pH on the treatment performance of the selected tertiary treatment scheme. In separate experiments, the impact of virgin GAC ozonation on its adsorptive capacity for biotreated and biotreated + ozonated textile effluent was also investigated. Ozonation appeared to be more effective for decolorization (kd = 0.15 min(-1) at pH = 3), whereas GAC adsorption yielded higher COD removal rates (54% at pH = 3). It was also found that GAC addition (4 g/L) at pH = 7 and 9 enhanced the COD abatement rate of the ozonation process significantly and that the sequential application of ozonation (at pH = 3-11, 675 mg L(-1) O3) followed by GAC adsorption (at pH = 3-7, 10 g L(-1) GAC) resulted in the highest treatment performances both in terms of color and COD reduction. Simultaneous application of GAC and ozone at acidic and alkaline pH seriously inhibited COD abatement rates as a consequence of competitive adsorption and partial oxidation of textile components and GAC. It could also be established that ozone absorption efficiency decreased after color removal was complete. Ozonation of biotreated textile wastewater with 113 mg L(-1) ozone resulted in an appreciable enhancement of GAC adsorptive capacity in terms of residual color removal. Ozonation of GAC at relatively low doses (= 10.8 mg/g GAC) did not improve its overall adsorption capacity.

Personal exposure to fine particulate air pollution while commuting: An examination of six transport modes on an urban arterial roadway.

PubMed

Chaney, Robert A; Sloan, Chantel D; Cooper, Victoria C; Robinson, Daniel R; Hendrickson, Nathan R; McCord, Tyler A; Johnston, James D

2017-01-01

Traffic-related air pollution in urban areas contributes significantly to commuters' daily PM2.5 exposures, but varies widely depending on mode of commuting. To date, studies show conflicting results for PM2.5 exposures based on mode of commuting, and few studies compare multiple modes of transportation simultaneously along a common route, making inter-modal comparisons difficult. In this study, we examined breathing zone PM2.5 exposures for six different modes of commuting (bicycle, walking, driving with windows open and closed, bus, and light-rail train) simultaneously on a single 2.7 km (1.68 mile) arterial urban route in Salt Lake City, Utah (USA) during peak "rush hour" times. Using previously published minute ventilation rates, we estimated the inhaled dose and exposure rate for each mode of commuting. Mean PM2.5 concentrations ranged from 5.20 μg/m3 for driving with windows closed to 15.21 μg/m3 for driving with windows open. The estimated inhaled doses over the 2.7 km route were 6.83 μg for walking, 2.78 μg for cycling, 1.28 μg for light-rail train, 1.24 μg for driving with windows open, 1.23 μg for bus, and 0.32 μg for driving with windows closed. Similarly, the exposure rates were highest for cycling (18.0 μg/hr) and walking (16.8 μg/hr), and lowest for driving with windows closed (3.7 μg/hr). Our findings support previous studies showing that active commuters receive a greater PM2.5 dose and have higher rates of exposure than commuters using automobiles or public transportation. Our findings also support previous studies showing that driving with windows closed is protective against traffic-related PM2.5 exposure.

Personal exposure to fine particulate air pollution while commuting: An examination of six transport modes on an urban arterial roadway

PubMed Central

Sloan, Chantel D.; Cooper, Victoria C.; Robinson, Daniel R.; Hendrickson, Nathan R.; McCord, Tyler A.; Johnston, James D.

2017-01-01

Traffic-related air pollution in urban areas contributes significantly to commuters’ daily PM2.5 exposures, but varies widely depending on mode of commuting. To date, studies show conflicting results for PM2.5 exposures based on mode of commuting, and few studies compare multiple modes of transportation simultaneously along a common route, making inter-modal comparisons difficult. In this study, we examined breathing zone PM2.5 exposures for six different modes of commuting (bicycle, walking, driving with windows open and closed, bus, and light-rail train) simultaneously on a single 2.7 km (1.68 mile) arterial urban route in Salt Lake City, Utah (USA) during peak “rush hour” times. Using previously published minute ventilation rates, we estimated the inhaled dose and exposure rate for each mode of commuting. Mean PM2.5 concentrations ranged from 5.20 μg/m3 for driving with windows closed to 15.21 μg/m3 for driving with windows open. The estimated inhaled doses over the 2.7 km route were 6.83 μg for walking, 2.78 μg for cycling, 1.28 μg for light-rail train, 1.24 μg for driving with windows open, 1.23 μg for bus, and 0.32 μg for driving with windows closed. Similarly, the exposure rates were highest for cycling (18.0 μg/hr) and walking (16.8 μg/hr), and lowest for driving with windows closed (3.7 μg/hr). Our findings support previous studies showing that active commuters receive a greater PM2.5 dose and have higher rates of exposure than commuters using automobiles or public transportation. Our findings also support previous studies showing that driving with windows closed is protective against traffic-related PM2.5 exposure. PMID:29121096

Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

PubMed Central

Koskiniemi, M.; Van Vleymen, B.; Hakamies, L.; Lamusuo, S.; Taalas, J.

1998-01-01

OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage.

 PMID:9527146

[Brachytherapy for head and neck cancers].

PubMed

Peiffert, D; Coche-Dequéant, B; Lapeyre, M; Renard, S

2018-05-29

The main indications of the brachytherapy of head and neck cancers are the limited tumours of the lip, the nose, the oral cavity and the oropharynx. Nasopharynx tumours are nowadays treated by intensity-modulated radiotherapy. This technique can be exclusive, associated with external radiotherapy or postoperative. It can also be a salvage treatment for the second primaries in previously irradiated areas. If the low dose rate brachytherapy rules remain the reference, the pulse dose rate technique allows the prescription of the dose rate and the optimisation of the dose distribution. Results of high dose rate brachytherapy are now published. This paper reports the recommendations of the Gec-ESTRO, published in 2017, and takes into account the data of the historical low dose rate series, and is upgraded with the pulsed-dose rate and high dose rate series. Copyright © 2018. Published by Elsevier SAS.

Hypothyroidism after Radiation Therapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

PubMed

Inskip, Peter D; Veiga, Lene H S; Brenner, Alina V; Sigurdson, Alice J; Ostroumova, Evgenia; Chow, Eric J; Stovall, Marilyn; Smith, Susan A; Weathers, Rita E; Leisenring, Wendy; Robison, Leslie L; Armstrong, Gregory T; Sklar, Charles A; Lubin, Jay H

2018-05-15

While thyroid cancer risks from exposure to ionizing radiation early in life are well characterized quantitatively, the association of radiation with nonmalignant, functional thyroid disorders has been less studied. Here, we report on a risk analysis study of hypothyroidism with radiation dose to the thyroid gland and the hypothalamic-pituitary axis among survivors of childhood cancer. Utilizing data from the Childhood Cancer Survivor Study, a cohort of 14,364 five-year survivors of childhood cancer diagnosed at 26 hospitals in the U.S. and Canada between 1970 and 1986 and followed through 2009, the occurrence of hypothyroidism was ascertained among 12,015 survivors through serial questionnaires. Radiation doses to the thyroid gland and pituitary gland were estimated from radiotherapy records. Binary outcome regression was used to estimate prevalence odds ratios for hypothyroidism at five years from diagnosis of childhood cancer and Poisson regression to model incidence rate ratios (RR) after the first five years. A total of 1,193 cases of hypothyroidism were observed, 777 (65%) of which occurred five or more years after cancer diagnosis. The cumulative proportion affected with hypothyroidism (prevalence at five years after cancer diagnosis plus incidence through 30 years after cancer diagnosis) was highest among five-year survivors of Hodgkin lymphoma (32.3%; 95% CI: 29.5-34.9) and cancers of the central nervous system (17.7%; 95% CI: 15.2-20.4). The incidence rate was significantly associated with radiation dose to the thyroid and pituitary. The joint association of hypothyroidism with thyroid and pituitary dose was sub-additive for pituitary doses greater than 16 Gy. In particular, a very strong thyroid radiation dose dependence at low-to-moderate pituitary/hypothalamic doses was diminished at high pituitary doses. Radiation-related risks were higher in males than females and inversely associated with age at exposure and time since exposure but remained elevated more than 25 years after exposure. Our findings indicated that hypothyroidism was significantly associated with treatment with bleomycin (RR = 3.4; 95% CI: 1.6-7.3) and the alkylating agents cyclohexyl-chloroethyl-nitrosourea (CCNU) (RR = 3.0; 95% CI: 1.5-5.3) and cyclophosphamide (RR = 1.3; 95% CI: 1.0-1.8), with a significant dose response for CCNU ( P < 0.01). The risk of hypothyroidism among childhood cancer survivors treated with radiation depends both on direct, dose-dependent radiation-induced damage to the thyroid gland and on dose-dependent indirect effects secondary to irradiation of the hypothalamic-pituitary axis. The dose-response relationship for each site depends on dose to the other. Radiation-related risk persists for more than 25 years after treatment. Treatment with certain chemotherapy agents may increase the risk of hypothyroidism.

Temporal Stability of Multiple Response Systems to 7.5% Carbon Dioxide Challenge

PubMed Central

Roberson-Nay, Roxann; Gorlin, Eugenia I.; Beadel, Jessica R.; Cash, Therese; Vrana, Scott; Teachman, Bethany A.

2017-01-01

Self-reported anxiety, and potentially physiological response, to maintained inhalation of carbon dioxide (CO2) enriched air shows promise as a putative marker of panic reactivity and vulnerability. Temporal stability of response systems during low-dose, steady-state CO2 breathing challenge is lacking. Outcomes on multiple levels were measured two times, one week apart, in 93 individuals. Stability was highest during the CO2 breathing phase compared to pre-CO2 and recovery phases, with anxiety ratings, respiratory rate, skin conductance level, and heart rate demonstrating good to excellent temporal stability (ICCs ≥ 0.71). Cognitive symptoms tied to panic were somewhat less stable (ICC = 0.58) than physical symptoms (ICC = 0.74) during CO2 breathing. Escape/avoidance behaviors and DSM-5 panic attacks were not stable. Large effect sizes between task phases also were observed. Overall, results suggest good-excellent levels of temporal stability for multiple outcomes during respiratory stimulation via 7.5% CO2. PMID:28163046

Vector competence of Australian mosquitoes for yellow fever virus.

PubMed

van den Hurk, Andrew F; McElroy, Kate; Pyke, Alyssa T; McGee, Charles E; Hall-Mendelin, Sonja; Day, Andrew; Ryan, Peter A; Ritchie, Scott A; Vanlandingham, Dana L; Higgs, Stephen

2011-09-01

The vector competence of Australian mosquitoes for yellow fever virus (YFV) was evaluated. Infection and transmission rates in Cairns and Townsville populations of Aedes aegypti and a Brisbane strain of Ae. notoscriptus were not significantly different from a well-characterized YFV-susceptible strain of Ae. aegypti. After exposure to 10⁷·² tissue culture infectious dose (TCID₅₀)/mL of an African strain of YFV, > 70% of Ae. aegypti and Ae. notoscriptus became infected, and > 50% transmitted the virus. When exposed to 10⁶·⁷) TCID₅₀/mL of a South American strain of YFV, the highest infection (64%) and transmission (56%) rates were observed in Ae. notoscriptus. The infection and transmission rates in the Cairns Ae. aegypti were both 24%, and they were 36% and 28%, respectively, for the Townsville population. Because competent vectors are present, the limited number of travelers from endemic areas and strict vaccination requirements will influence whether YFV transmission occurs in Australia.

An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

NASA Astrophysics Data System (ADS)

Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

2015-04-01

Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

Modification of soil microbial activity and several hydrolases in a forest soil artificially contaminated with copper

NASA Astrophysics Data System (ADS)

Bellas, Rosa; Leirós, Mā Carmen; Gil-Sotres, Fernando; Trasar-Cepeda, Carmen

2010-05-01

Soils have long been exposed to the adverse effects of human activities, which negatively affect soil biological activity. As a result of their functions and ubiquitous presence microorganisms can serve as environmental indicators of soil pollution. Some features of soil microorganisms, such as the microbial biomass size, respiration rate, and enzyme activity are often used as bioindicators of the ecotoxicity of heavy metals. Although copper is essential for microorganisms, excessive concentrations have a negative influence on processes mediated by microorganisms. In this study we measured the response of some microbial indicators to Cu pollution in a forest soil, with the aim of evaluating their potential for predicting Cu contamination. Samples of an Ah horizon from a forest soil under oakwood vegetation (Quercus robur L.) were contaminated in the laboratory with copper added at different doses (0, 120, 360, 1080 and 3240 mg kg-1) as CuCl2×2H2O. The soil samples were kept for 7 days at 25 °C and at a moisture content corresponding to the water holding capacity, and thereafter were analysed for carbon and nitrogen mineralization capacity, microbial biomass C, seed germination and root elongation tests, and for urease, phosphomonoesterase, catalase and ß-glucosidase activities. In addition, carbon mineralization kinetics were studied, by plotting the log of residual C against incubation time, and the metabolic coefficient, qCO2, was estimated. Both organic carbon and nitrogen mineralization were lower in polluted samples, with the greatest decrease observed in the sample contaminated with 1080 mg kg-1. In all samples carbon mineralization followed first order kinetics; the C mineralization constant was lower in contaminated than in uncontaminated samples and, in general, decreased with increasing doses of copper. Moreover, it appears that copper contamination not only reduced the N mineralization capacity, but also modified the N mineralization process, since in the contaminated samples all of the inorganic nitrogen was present as ammonium, probably because of inhibition of nitrification. There was a marked decrease in biomass-C with addition of copper, and the decrease was more acute at intermediate doses (average decrease, 73%). Despite the decreases in microbial biomass and mineralized C, the value of qCO2 increased after the addition of copper. Urease activity was strongly affected by the presence of copper and the decrease was proportional to the dose; the activity at the highest dose was only 96% of that in the uncontaminated sample. Phosphomonoesterase activity was also affected by addition of copper; the reduction in activity was less than for urease and the greatest reduction was observed for the dose of 1080 mg kg-1 of copper. Catalase activity was affected by the contamination, but no clear trend was observed in relation to the dose of copper. ß-glucosidase was scarcely modified by the contamination but an increase in activity was observed at the highest dose of copper. Seed germination was not affected by copper contamination, since it only showed a clear decrease for the sample contaminated with the highest dose of copper, while root elongation decreased sharply with doses higher than 120 mg kg-1 of copper. The combined germination-elongation index followed a similar pattern to that of root elongation. For all investigated properties showing a reduction of more than 50%, the response to copper contamination was fitted to a sigmoidal dose-response model, in order to estimate the ED50 values. The ED50 values were calculated for microbial biomass, urease, root elongation and germination-elongation index, and similar values were obtained, ranging from 340 to 405 mg kg-1 Cu. The ED50 values may therefore provide a good estimation of soil deterioration.

Individual and combined effects of multiple pathogens on Pacific treefrogs.

PubMed

Romansic, John M; Johnson, Pieter T J; Searle, Catherine L; Johnson, James E; Tunstall, Tate S; Han, Barbara A; Rohr, Jason R; Blaustein, Andrew R

2011-08-01

In nature, individual hosts often encounter multiple pathogens simultaneously, which can lead to additive, antagonistic, or synergistic effects on hosts. Synergistic effects on infection prevalence or severity could greatly affect host populations. However, ecologists and managers often overlook the influence of pathogen combinations on hosts. This is especially true in amphibian conservation, even though multiple pathogens coexist within amphibian populations, and several pathogens have been implicated in amphibian population declines and extinctions. Using an amphibian host, Pseudacris regilla (Pacific treefrog), we experimentally investigated interactive effects among three pathogens: the trematode Ribeiroia sp. (hereafter, Ribeiroia), the fungus Batrachochytrium dendrobatidis (hereafter, BD), and the water mold Achlya flagellata. We detected no effects of A. flagellata, but did find effects of Ribeiroia and BD that varied depending on context. Low doses of Ribeiroia caused relatively few malformations, while higher Ribeiroia doses caused numerous deformities dominated by missing and reduced limbs and limb elements. Exposure to low doses of BD accelerated larval host development, despite there being no detectable BD infections, while exposure to higher BD doses caused infection but did not alter developmental rate. Hosts exposed to both Ribeiroia and BD exhibited the highest mortality, although overall evidence of interactive effects of multiple pathogens was limited. We suggest further research on the influence of multi-pathogen assemblages on amphibians, particularly under a variety of ecological conditions and with a wider diversity of hosts and pathogens.

Estimation of annual effective dose due to natural radioactive elements in ingestion of foodstuffs in tin mining area of Jos-Plateau, Nigeria.

PubMed

Jibiri, N N; Farai, I P; Alausa, S K

2007-01-01

Soils and food crops from a former tin mining location in a high background radiation area on the Jos-Plateau, Nigeria were collected and analyzed by gamma spectrometry to measure their contents of 40K, 238U and 232Th. As well as collecting samples, in situ dose rates on farms were measured using a precalibrated survey meter. Activity concentrations determined in food crops were compared with the local food derivatives or diets to investigate the possible removal or addition of radionuclides during food preparation by cooking or other means. Potassium-40 was found to contribute the highest activity in all the food products. The activity concentration of 40K, 238U and 232Th in local prepared diets ranged between 60 and 494 Bq kg-1, between BDL and 48 Bq kg-1 and between BDL and 17 Bq kg-1, respectively. The internal effective dose to individuals from the consumption of the food types was estimated on the basis of the measured radionuclide contents in the food crops. It ranged between 0.2 microSv y-1 (beans) and 2164 microSv y-1 (yam) while the annual external gamma effective dose in the farms due to soil radioactivity ranged between 228 microSv and 4065 microSv.

Cardiovascular effects of Nemopilema nomurai (Scyphozoa: Rhizostomeae) jellyfish venom in rats.

PubMed

Kim, Euikyung; Lee, Seunghwan; Kim, Jong-Shu; Yoon, Won Duk; Lim, Donghyun; Hart, Andrew J; Hodgson, Wayne C

2006-12-15

Over the past few years, populations of the giant jellyfish Nemopilema nomurai (Scyphozoa: Rhizostomeae) have increased dramatically in the waters of China, Korea, and Japan without any definitive reason. This has resulted in severe damage to fisheries in the areas. During a pilot study, we observed that the venom of N. nomurai produced a functional cardiac depression in mice. However, the mechanism of action was not examined. In the present study, we investigated the cardiovascular effects of nematocyst-derived venom from N. nomurai in anesthetized rats. Venom (0.1-2.4 mg protein/kg, i.v.) produced dose-dependent hypotension (65+/-12% of initial at a cumulative dose of 3 mg/kg) and bradycardia (80+/-5% of initial at a cumulative dose of 3 mg/kg). At the highest dose, this was characterized by a transient decrease in blood pressure (phase 1) followed by a return to basal level and then a slower decrease in blood pressure (phase 2). Venom also produced a decrease in rate and force of contraction in the rat isolated atria. Interestingly, venom induced a contraction of isolated aortic rings which was blocked by felodipine but not by prazosin, suggesting the contraction is mediated by calcium channel activation. These results suggest that the negative inotropic and chronotropic effects of the venom of N. nomurai may be due to a direct effect on the heart.

Leuco-crystal-violet micelle gel dosimeters: Component effects on dose-rate dependence

NASA Astrophysics Data System (ADS)

Xie, J. C.; Katz, E. A. B.; Alexander, K. M.; Schreiner, L. J.; McAuley, K. B.

2017-05-01

Designed experiments were performed to produce empirical models for the dose sensitivity, initial absorbance, and dose-rate dependence respectively for leucocrystal violet (LCV) micelle gel dosimeters containing cetyltrimethylammonium bromide (CTAB) and 2,2,2-trichloroethanol (TCE). Previous gels of this type showed dose-rate dependent behaviour, producing an ˜18% increase in dose sensitivity between dose rates of 100 and 600 cGy min-1. Our models predict that the dose rate dependence can be reduced by increasing the concentration of TCE, CTAB and LCV. Increasing concentrations of LCV and CTAB produces a significant increase in dose sensitivity with a corresponding increase in initial absorbance. An optimization procedure was used to determine a nearly dose-rate independent gel which maintained high sensitivity and low initial absorbance. This gel which contains 33 mM CTAB, 1.25 mM LCV, and 96 mM TCE in 25 mM trichloroacetic acid and 4 wt% gelatin showed an increase in dose sensitivity of only 4% between dose rates of 100 and 600 cGy min-1, and provides an 80% greater dose sensitivity compared to Jordan’s standard gels with similar initial absorbance.

Dose and dose rate effects of whole-body gamma-irradiation: I. Lymphocytes and lymphoid organs

NASA Technical Reports Server (NTRS)

Pecaut, M. J.; Nelson, G. A.; Gridley, D. S.

2001-01-01

The major goal of part I of this study was to compare varying doses and dose rates of whole-body gamma-radiation on lymphoid cells and organs. C57BL/6 mice (n = 75) were exposed to 0, 0.5, 1.5, and 3.0 Gy gamma-rays (60Co) at 1 cGy/min (low-dose rate, LDR) and 80 cGy/min (high-dose rate, HDR) and euthanized 4 days later. A significant dose-dependent loss of spleen mass was observed with both LDR and HDR irradiation; for the thymus this was true only with HDR. Decreasing leukocyte and lymphocyte numbers occurred with increasing dose in blood and spleen at both dose rates. The numbers (not percentages) of CD3+ T lymphocytes decreased in the blood in a dose-dependent manner at both HDR and LDR. Splenic T cell counts decreased with dose only in HDR groups; percentages increased with dose at both dose rates. Dose-dependent decreases occurred in CD4+ T helper and CD8+ T cytotoxic cell counts at HDR and LDR. In the blood the percentages of CD4+ cells increased with increasing dose at both dose rates, whereas in the spleen the counts decreased only in the HDR groups. The percentages of the CD8+ population remained stable in both blood and spleen. CD19+ B cell counts and percentages in both compartments declined markedly with increasing HDR and LDR radiation. NK1.1+ natural killer cell numbers and proportions remained relatively stable. Overall, these data indicate that the observed changes were highly dependent on the dose, but not dose rate, and that cells in the spleen are more affected by dose rate than those in blood. The results also suggest that the response of lymphocytes in different body compartments may be variable.

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Using RADFET for the real-time measurement of gamma radiation dose rate

NASA Astrophysics Data System (ADS)

Andjelković, Marko S.; Ristić, Goran S.; Jakšić, Aleksandar B.

2015-02-01

RADFETs (RADiation sensitive Field Effect Transistors) are integrating ionizing radiation dosimeters operating on the principle of conversion of radiation-induced threshold voltage shift into absorbed dose. However, one of the major drawbacks of RADFETs is the inability to provide the information on the dose rate in real-time using the conventional absorbed dose measurement technique. The real-time monitoring of dose rate and absorbed dose can be achieved with the current mode dosimeters such as PN and PIN diodes/photodiodes, but these dosimeters have some limitations as absorbed dose meters and hence they are often not a suitable replacement for RADFETs. In that sense, this paper investigates the possibility of using the RADFET as a real-time dose rate meter so that it could be applied for simultaneous online measurement of the dose rate and absorbed dose. A RADFET sample, manufactured by Tyndall National Institute, Cork, Ireland, was tested as a dose rate meter under gamma irradiation from a Co-60 source. The RADFET was configured as a PN junction, such that the drain, gate and source terminals were grounded, while the radiation-induced current was measured at the bulk terminal, whereby the bulk was successively biased with 0 , 10 , 20  and 30 V. In zero-bias mode the radiation-induced current was unstable, but in the biased mode the current response was stable for the investigated dose rates from 0.65  to 32.1 Gy h-1 and up to the total absorbed dose of 25 Gy. The current increased with the dose rate in accordance with the power law, whereas the sensitivity of the current read-out was linear with respect to the applied bias voltage. Comparison with previously analyzed PIN photodiodes has shown that the investigated RADFET is competitive with PIN photodiodes as a gamma radiation dose rate meter and therefore has the potential to be employed for the real-time monitoring of the dose rate and absorbed dose.

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

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

Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth

2008-08-01

Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissuemore » dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.« less

Lung Cancer Screening May Benefit Those at Highest Risk

Cancer.gov

People at the highest risk for lung cancer, based on a risk model, may be more likely to benefit from screening with low-dose CT, a new analysis suggests. The study authors believe the findings may better define who should undergo lung cancer screening, as this Cancer Currents blog post explains.

Comparison of childhood thyroid cancer prevalence among 3 areas based on external radiation dose after the Fukushima Daiichi nuclear power plant accident

PubMed Central

Ohira, Tetsuya; Takahashi, Hideto; Yasumura, Seiji; Ohtsuru, Akira; Midorikawa, Sanae; Suzuki, Satoru; Fukushima, Toshihiko; Shimura, Hiroki; Ishikawa, Tetsuo; Sakai, Akira; Yamashita, Shunichi; Tanigawa, Koichi; Ohto, Hitoshi; Abe, Masafumi; Suzuki, Shinichi

2016-01-01

Abstract The 2011 Great East Japan Earthquake led to a subsequent nuclear accident at the Fukushima Daiichi Nuclear Power Plant. In its wake, we sought to examine the association between external radiation dose and thyroid cancer in Fukushima Prefecture. We applied a cross-sectional study design with 300,476 participants aged 18 years and younger who underwent thyroid examinations between October 2011 and June 2015. Areas within Fukushima Prefecture were divided into three groups based on individual external doses (≥1% of 5 mSv, <99% of 1 mSv/y, and the other). The odds ratios (ORs) and 95% confidence intervals of thyroid cancer for all areas, with the lowest dose area as reference, were calculated using logistic regression models adjusted for age and sex. Furthermore, the ORs of thyroid cancer for individual external doses of 1 mSv or more and 2 mSv or more, with the external dose less than 1 mSv as reference, were calculated. Prevalence of thyroid cancer for the location groups were 48/100,000 for the highest dose area, 36/100,000 for the middle dose area, and 41/100,000 for the lowest dose area. Compared with the lowest dose area, age-, and sex-adjusted ORs (95% confidence intervals) for the highest-dose and middle-dose areas were 1.49 (0.36–6.23) and 1.00 (0.67–1.50), respectively. The duration between accident and thyroid examination was not associated with thyroid cancer prevalence. There were no significant associations between individual external doses and prevalence of thyroid cancer. External radiation dose was not associated with thyroid cancer prevalence among Fukushima children within the first 4 years after the nuclear accident. PMID:27583855

Comparison of childhood thyroid cancer prevalence among 3 areas based on external radiation dose after the Fukushima Daiichi nuclear power plant accident: The Fukushima health management survey.

PubMed

Ohira, Tetsuya; Takahashi, Hideto; Yasumura, Seiji; Ohtsuru, Akira; Midorikawa, Sanae; Suzuki, Satoru; Fukushima, Toshihiko; Shimura, Hiroki; Ishikawa, Tetsuo; Sakai, Akira; Yamashita, Shunichi; Tanigawa, Koichi; Ohto, Hitoshi; Abe, Masafumi; Suzuki, Shinichi

2016-08-01

The 2011 Great East Japan Earthquake led to a subsequent nuclear accident at the Fukushima Daiichi Nuclear Power Plant. In its wake, we sought to examine the association between external radiation dose and thyroid cancer in Fukushima Prefecture. We applied a cross-sectional study design with 300,476 participants aged 18 years and younger who underwent thyroid examinations between October 2011 and June 2015. Areas within Fukushima Prefecture were divided into three groups based on individual external doses (≥1% of 5 mSv, <99% of 1 mSv/y, and the other). The odds ratios (ORs) and 95% confidence intervals of thyroid cancer for all areas, with the lowest dose area as reference, were calculated using logistic regression models adjusted for age and sex. Furthermore, the ORs of thyroid cancer for individual external doses of 1 mSv or more and 2 mSv or more, with the external dose less than 1 mSv as reference, were calculated. Prevalence of thyroid cancer for the location groups were 48/100,000 for the highest dose area, 36/100,000 for the middle dose area, and 41/100,000 for the lowest dose area. Compared with the lowest dose area, age-, and sex-adjusted ORs (95% confidence intervals) for the highest-dose and middle-dose areas were 1.49 (0.36-6.23) and 1.00 (0.67-1.50), respectively. The duration between accident and thyroid examination was not associated with thyroid cancer prevalence. There were no significant associations between individual external doses and prevalence of thyroid cancer. External radiation dose was not associated with thyroid cancer prevalence among Fukushima children within the first 4 years after the nuclear accident.

Improved Nitrogen Removal Effect In Continuous Flow A2/O Process Using Typical Extra Carbon Source

NASA Astrophysics Data System (ADS)

Wu, Haiyan; Gao, Junyan; Yang, Dianhai; Zhou, Qi; Cai, Bijing

2010-11-01

In order to provide a basis for optimal selection of carbon source, three typical external carbon sources (i.e. methanol, sodium acetate and leachate) were applied to examine nitrogen removal efficiency of continuous flow A2/O system with the influent from the effluent of grit chamber in the second Kunming wastewater treatment plant. The best dosage was determined, and the specific nitrogen removal rate and carbon consumption rate were calculated with regard to individual external carbon source in A2/O system. Economy and technology analysis was also conducted to select the suitable carbon source with a low operation cost. Experimental results showed that the external typical carbon source caused a remarkable enhancement of system nitrate degradation ability. In comparison with the blank test, the average TN and NH3-N removal efficiency of system with different dosing quantities of external carbon source was improved by 15.2% and 34.2%, respectively. The optimal dosage of methanol, sodium acetate and leachate was respectively up to 30 mg/L, 40 mg/L and 100 mg COD/L in terms of a high nitrogen degradation effect. The highest removal efficiency of COD, TN and NH3-N reached respectively 92.3%, 73.9% and 100% with methanol with a dosage of 30 mg/L. The kinetic analysis and calculation revealed that the greatest denitrification rate was 0.0107 mg TN/mg MLVSSṡd with sodium acetate of 60 mg/L. As to carbon consumption rate, however, the highest value occurred in the blank test with a rate of 0.1955 mg COD/mg MLVSSṡd. Also, further economic analysis proved leachate to be pragmatic external carbon source whose cost was far cheaper than methanol.

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

PubMed

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

Rapid Acute Dose Assessment Using MCNP6

NASA Astrophysics Data System (ADS)

Owens, Andrew Steven

Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.

5 CFR 532.405 - Use of highest previous rate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Use of highest previous rate. 532.405 Section 532.405 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Pay Administration § 532.405 Use of highest previous rate. (a)(1) Subject to the...

AREA RADIATION MONITOR

DOEpatents

Manning, F.W.; Groothuis, S.E.; Lykins, J.H.; Papke, D.M.

1962-06-12

S>An improved area radiation dose monitor is designed which is adapted to compensate continuously for background radiation below a threshold dose rate and to give warning when the dose integral of the dose rate of an above-threshold radiation excursion exceeds a selected value. This is accomplished by providing means for continuously charging an ionization chamber. The chamber provides a first current proportional to the incident radiation dose rate. Means are provided for generating a second current including means for nulling out the first current with the second current at all values of the first current corresponding to dose rates below a selected threshold dose rate value. The second current has a maximum value corresponding to that of the first current at the threshold dose rate. The excess of the first current over the second current, which occurs above the threshold, is integrated and an alarm is given at a selected integrated value of the excess corresponding to a selected radiation dose. (AEC)

miR-26b enhances radiosensitivity of hepatocellular carcinoma cells by targeting EphA2

PubMed Central

Jin, Qiao; Li, Xiang Jun; Cao, Pei Guo

2016-01-01

Objective(s): Although low-dose radiotherapy (RT) that involves low collateral damage is more suitable for hepatocellular carcinoma (HCC) than traditional high-dose RT, but to achieve satisfactory therapeutic effect with low-dose RT, it is necessary to sensitize HCC cells to irradiation. This study was aimed to determine whether radiosensitivity of HCC cells can be enhanced using miR-26b by targeting erythropoietin producing human hepatocelluar A2 (EphA2). Materials and Methods: The levels of miR-26b and EphA2 expression in multiple HCC cell lines were assessed by qPCR and western blotting, respectively, and compared with those in a hepatic cell line. HCC 97H cells were transfected with miR-26b mimics, EphA2-ShRNA or EphA2 over-expression vector before exposure to low-dose irradiation. Results: Different degrees of miR-26b down-regulation and EphA2 up-regulation were observed in all HCC cell lines, among which the HCC 97H cell line expressed the lowest level of miR-26b and highest level of EphA2. EphA2 was verified as the target of miR-26b by dual luciferase reporter assay. HCC 97H cells transfected with miR-26b mimics or EphA2-ShRNA reduced the expression of EphA2 protein, with significantly lower cell proliferation rate and cell invasion ability and higher apoptosis rate in response to low-dose irradiation than those in the non-transfected cells. These results were reversed after EphA2 was overexpressed by transfection with the EphA2 overexpression vector. Co-transfection with miR-26b mimics and EphA2 overexpression vector barely altered EphA2 expression level and cell response to low-dose irradiation. Conclusion: These data suggest that miR-26b enhances radiosensitivity of HCC 97H cells by targeting EphA2 protein. PMID:27746866

GAL-021, a new intravenous BKCa-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers.

PubMed

McLeod, J F; Leempoels, J M; Peng, S X; Dax, S L; Myers, L J; Golder, F J

2014-11-01

Potassium-channels in the carotid body and the brainstem are important regulators of ventilation. The BKCa-channel contains response elements for CO, O2, and CO2. Its block increases carotid body signalling, phrenic nerve activity, and respiratory drive. GAL-021, a new BKCa-channel blocker, increases minute ventilation in rats and non-human primates. This study assessed the single-dose safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of GAL-021 in healthy volunteers. Thirty subjects participated in a nine-period, randomized, double-blinded, placebo-controlled, crossover, ascending dose, first-in-human study with i.v. infusions of 0.1-0.96 mg kg(-1) h(-1) for 1 h and intermediate doses up to 4 h. Adverse event rates were generally similar among dose levels and between placebo- and GAL-021-treated subjects. At higher GAL-021 doses, a mild/moderate burning sensation at the infusion site occurred during the infusion. No clinically significant changes in vital signs or clinical chemistries were noted. Minute ventilation increased (AUE0-1 h ≈ 16%, P<0.05) and end-tidal carbon dioxide ([Formula: see text]) decreased (AUE0-1 h ≈ 6%, P<0.05) during the first hour at 0.96 mg kg(-1) h(-1) with 1/2-maximal [Formula: see text] and [Formula: see text]-change occurring by 7.5 min. Drug concentration rose rapidly during the infusion and decreased rapidly initially (distribution t1/2 of 30 min) and then more slowly (terminal t1/2 of 5.6 h). GAL-021 was safe and generally well tolerated with adverse events comparable with placebo except for an infusion site burning sensation. GAL-021 stimulated ventilation at the highest doses suggesting that greater infusion rates may be required for maximum PD effects. GAL-021 had PK characteristics consistent with an acute care medication. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

Impact of the Amount of Liquid Intake on the Dose Rate of Patients Treated with Radioiodine.

PubMed

Haghighatafshar, Mahdi; Banani, Aida; Zeinali-Rafsanjani, Banafsheh; Etemadi, Zahra; Ghaedian, Tahereh

2018-01-01

Despite therapeutic effects of radioiodine in patients with differentiated thyroid cancer, there are some disadvantages due to harmful radiation to other tissues. According to the current guidelines, patients are recommended to drink lots of water and frequent voiding to reduce the amount of 131 I in the body. This study was designed to assess the impact of the amount of liquid intake on reduction of the measured dose rate of radioiodine-treated patients. A total of 42 patients with differentiated thyroid cancer without metastasis who had undergone total thyroidectomy and had been treated with radioiodine were selected. The patients were divided into two groups according to the amount of their fluid intake which was measured during the first 48 h after 131 I administration. In all patients, the dose rate was measured immediately and 48 h after iodine administration. Each group included 21 patients. Dose rate ratio (the ratio of the second dose rate to the first dose rate) and dose rate difference ratio (the ratio of the difference between the two measured dose rates to the first dose rate) were calculated for each patient. Despite the significant difference in the amount of the liquid drunk, no statistically significant difference was seen between the different groups in parameters of dose-rate ratio and dose-rate difference ratio. Higher fluid intake (>60 ml/h in our study) alone would not effectively reduce the patient's radiation dose rate at least not more than a well-hydrated state. It seems that other interfering factors in the thyroidectomized patients may also have some impacts on this physiologic process.

The combination of compost addition and arbuscular mycorrhizal inoculation produced positive and synergistic effects on the phytomanagement of a semiarid mine tailing.

PubMed

Kohler, J; Caravaca, F; Azcón, R; Díaz, G; Roldán, A

2015-05-01

A field experiment was carried out to assess the effectiveness of combining mycorrhizal inoculation with a native AM fungus (Glomus sp.) and the addition of an urban organic waste compost (OWC) applied at two rates (0.5 and 2.0% (w:w)), with regard to promoting the establishment of Anthyllis cytisoides L. seedlings in a heavy metal polluted mine tailing, as well as stimulating soil microbial functions. The results showed that the combined use of the highest dose of OWC and AM inoculation significantly increased shoot biomass - by 64% - compared to the control value. However, the separate use of each treatment had no effect on the shoot biomass of this shrub species. At the 2% rate, OWC enhanced root colonisation by the introduced fungus as well as soil nutrient content and soil dehydrogenase and ß-glucosidase activities. The combined treatment increased the uptake of Zn and Mn in shoots, although only Zn reached excessive or potentially toxic levels. This study demonstrates that the combination of organic amendment and an AM fungus is a suitable tool for the phytomanagement of degraded mine tailings, although its effectiveness is dependent on the dose of the amendment. Copyright © 2015 Elsevier B.V. All rights reserved.

Time Profile of Cosmic Radiation Exposure During the EXPOSE-E Mission: The R3DE Instrument

PubMed Central

Horneck, Gerda; Häder, Donat-Peter; Schuster, Martin; Richter, Peter; Lebert, Michael; Demets, Rene

2012-01-01

Abstract The aim of this paper is to present the time profile of cosmic radiation exposure obtained by the Radiation Risk Radiometer-Dosimeter during the EXPOSE-E mission in the European Technology Exposure Facility on the International Space Station's Columbus module. Another aim is to make the obtained results available to other EXPOSE-E teams for use in their data analysis. Radiation Risk Radiometer-Dosimeter is a low-mass and small-dimension automatic device that measures solar radiation in four channels and cosmic ionizing radiation as well. The main results of the present study include the following: (1) three different radiation sources were detected and quantified—galactic cosmic rays (GCR), energetic protons from the South Atlantic Anomaly (SAA) region of the inner radiation belt, and energetic electrons from the outer radiation belt (ORB); (2) the highest daily averaged absorbed dose rate of 426 μGy d−1 came from SAA protons; (3) GCR delivered a much smaller daily absorbed dose rate of 91.1 μGy d−1, and the ORB source delivered only 8.6 μGy d−1. The analysis of the UV and temperature data is a subject of another article (Schuster et al., 2012). Key Words: Ionizing radiation—R3D—ISS. Astrobiology 12, 403–411. PMID:22680687

Ultralow dose dentomaxillofacial CT imaging and iterative reconstruction techniques: variability of Hounsfield units and contrast-to-noise ratio

PubMed Central

Bischel, Alexander; Stratis, Andreas; Kakar, Apoorv; Bosmans, Hilde; Jacobs, Reinhilde; Gassner, Eva-Maria; Puelacher, Wolfgang; Pauwels, Ruben

2016-01-01

Objective: The aim of this study was to evaluate whether application of ultralow dose protocols and iterative reconstruction technology (IRT) influence quantitative Hounsfield units (HUs) and contrast-to-noise ratio (CNR) in dentomaxillofacial CT imaging. Methods: A phantom with inserts of five types of materials was scanned using protocols for (a) a clinical reference for navigated surgery (CT dose index volume 36.58 mGy), (b) low-dose sinus imaging (18.28 mGy) and (c) four ultralow dose imaging (4.14, 2.63, 0.99 and 0.53 mGy). All images were reconstructed using: (i) filtered back projection (FBP); (ii) IRT: adaptive statistical iterative reconstruction-50 (ASIR-50), ASIR-100 and model-based iterative reconstruction (MBIR); and (iii) standard (std) and bone kernel. Mean HU, CNR and average HU error after recalibration were determined. Each combination of protocols was compared using Friedman analysis of variance, followed by Dunn's multiple comparison test. Results: Pearson's sample correlation coefficients were all >0.99. Ultralow dose protocols using FBP showed errors of up to 273 HU. Std kernels had less HU variability than bone kernels. MBIR reduced the error value for the lowest dose protocol to 138 HU and retained the highest relative CNR. ASIR could not demonstrate significant advantages over FBP. Conclusions: Considering a potential dose reduction as low as 1.5% of a std protocol, ultralow dose protocols and IRT should be further tested for clinical dentomaxillofacial CT imaging. Advances in knowledge: HU as a surrogate for bone density may vary significantly in CT ultralow dose imaging. However, use of std kernels and MBIR technology reduce HU error values and may retain the highest CNR. PMID:26859336

Recommended de minimis radiation dose rates for Canada. Report No. INFO-0355

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

Not Available

1990-01-01

A de minimis dose or dose rate as used in this report represents a level of risk which is generally accepted as being of no significance to an individual, or in the case of a population, of no significance to society. The report describes the risk of biological effects from radiation; radiation from natural and man-made sources; normal incidences of cancer and genetic defects; initiatives by other agencies in the U.S., the U.K. and internationally; the importance of collective dose and dose rate; assigning values to the de minimis dose rates; and application of the de minimis dose rates.

Evaluation of the Effects of Lime-bassanite-charcoal Amendment on the Immobilization of Cadmium in Contaminated Soil.

PubMed

Huang, Shunhong; Yang, Yi; Li, Qian; Su, Zhen; Yuan, Cuiyu; Ouyang, Kun

2017-03-01

The effects of amendments, such as lime, bassanite, sodium phosphate, steel slag and charcoal, and their compounds on the immobilization of cadmium (Cd) are investigated. The lime-bassanite-charcoal compound shows the best remediation performance compared to other agents in conducted experiments. The optimum condition for lime-bassanite-charcoal application in contaminated soil is lime-bassanite-charcoal with a mass ratio of 1:1/3:2/3, a dose of 2% of the soil weight, and a liquid-to-solid ratio of 35%-40%; additionally, the agents should be added before water addition. The highest Cd removal rate was 58.94% (±1.19%) with a ∆pH of 0.23, which is much higher than the rates reported in previous studies. The compound amendment was used in a field experiment, demonstrating a Cd removal efficiency of 48.78% (±4.23), further confirming its effectiveness.

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents

PubMed Central

Vesikari, Timo; Østergaard, Lars; Diez-Domingo, Javier; Wysocki, Jacek; Flodmark, Carl-Erik; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U.; Jones, Thomas R.; Harris, Shannon L.; O'Neill, Robert E.; York, Laura J.; Crowther, Graham; Perez, John L.

2016-01-01

Background Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba®; bivalent rLP2086) was recently approved in the United States in individuals aged 10–25 years. Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents. Methods Healthy adolescents (11 to <19 years) were randomized to 1 of 5 bivalent rLP2086 dosing regimens (0,1,6-month; 0,2,6-month; 0,2-month; 0,4-month; 0,6-month). Immunogenicity was assessed by serum bactericidal antibody assay using human complement (hSBA). Safety assessments included local and systemic reactions and adverse events. Results Bivalent rLP2086 was immunogenic when administered as 2 or 3 doses; the most robust hSBA responses occurred with 3 doses. The proportion of subjects with hSBA titers ≥1:8 after 3 doses ranged from 91.7% to 95.0%, 98.9% to 99.4%, 88.4% to 89.0%, and 86.1% to 88.5% for MnB test strains expressing vaccine­-heterologous fHBP variants A22, A56, B24, and B44, respectively. After 2 doses, responses ranged from 90.8% to 93.5%, 98.4% to 100%, 69.1% to 81.1%, and 70.1% to 77.5%. Geometric mean titers (GMTs) were highest among subjects receiving 3 doses and similar between the 2- and 3-dose regimens. After 2 doses, GMTs trended numerically higher among subjects with longer intervals between the first and second dose (6 months vs 2 and 4 months). Bivalent rLP2086 was well tolerated. Conclusions Bivalent rLP2086 was immunogenic and well tolerated when administered in 2 or 3 doses. Three doses yielded the most robust hSBA response rates against MnB strains expressing vaccine-heterologous subfamily B fHBPs. PMID:26407272

TU-F-CAMPUS-T-04: An Evaluation of Out-Of-Field Doses for Electron Beams From Modern Varian and Elekta Linear Accelerators

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

Cardenas, C; Nitsch, P; Kudchadker, R

2015-06-15

Purpose: Accurately determining out-of-field doses when using electron beam radiotherapy is of importance when treating pregnant patients or patients with implanted electronic devices. Scattered doses outside of the applicator field in electron beams have not been broadly investigated, especially since manufacturers have taken different approaches in applicator designs. Methods: In this study, doses outside of the applicator field were measured for electron beams produced by a 10×10 applicator on two Varian 21iXs operating at 6, 9, 12, 16, and 20 MeV, a Varian TrueBeam operating at 6, 9, 12, 16, and 20 MeV, and an Elekta Versa HD operating atmore » 6, 9, 12 and 15 MeV. Peripheral dose profiles and percent depth doses were measured in a Wellhofer water phantom at 100 cm SSD with a Farmer ion chamber. Doses were compared to peripheral photon doses from AAPM’s Task Group #36 report. Results: Doses were highest for the highest electron energies. Doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. Substantial dose differences were observed between different accelerators; the Elekta accelerator had much higher doses than any Varian unit examined. Surprisingly, doses were often similar to, and could be much higher than, doses from photon therapy. Doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. Conclusion: The results of this study indicate that proper shielding may be very important when utilizing electron beams, particularly on a Versa HD, while treating pregnant patients or those with implanted electronic devices. Applying a water equivalent bolus of Emax(MeV)/4 thickness (cm) on the patient would reduce fetal dose drastically for all clinical energies and is a practical solution to manage the potentially high peripheral doses seen from modern electron beams. Funding from NIH Grant number: #CA180803.« less

Study of the dose rate effect of 180 nm nMOSFETs

NASA Astrophysics Data System (ADS)

He, Bao-Ping; Yao, Zhi-Bin; Sheng, Jiang-Kun; Wang, Zu-Jun; Huang, Shao-Yan; Liu, Min-Bo; Xiao, Zhi-Gang

2015-01-01

Radiation induced offstate leakage in the shallow trench isolation regions of SIMC 0.18 μm nMOSFETs is studied as a function of dose rate. A “true” dose rate effect (TDRE) is observed. Increased damage is observed at low dose rate (LDR) than at high dose rate (HDR) when annealing is taken into account. A new method of simulating radiation induced degradation in shallow trench isolation (STI) is presented. A comparison of radiation induced offstate leakage current in test nMOSFETs between total dose irradiation experiments and simulation results exhibits excellent agreement. The investigation results imply that the enhancement of the leakage current may be worse for the dose rate encountered in the environment of space.

Commuters’ Exposure to Particulate Matter Air Pollution Is Affected by Mode of Transport, Fuel Type, and Route

PubMed Central

Zuurbier, Moniek; Hoek, Gerard; Oldenwening, Marieke; Lenters, Virissa; Meliefste, Kees; van den Hazel, Peter; Brunekreef, Bert

2010-01-01

Background Commuters are exposed to high concentrations of air pollutants, but little quantitative information is currently available on differences in exposure between different modes of transport, routes, and fuel types. Objectives The aim of our study was to assess differences in commuters’ exposure to traffic-related air pollution related to transport mode, route, and fuel type. Methods We measured particle number counts (PNCs) and concentrations of PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter), PM10, and soot between June 2007 and June 2008 on 47 weekdays, from 0800 to 1000 hours, in diesel and electric buses, gasoline- and diesel-fueled cars, and along two bicycle routes with different traffic intensities in Arnhem, the Netherlands. In addition, each-day measurements were taken at an urban background location. Results We found that median PNC exposures were highest in diesel buses (38,500 particles/cm3) and for cyclists along the high-traffic intensity route (46,600 particles/cm3) and lowest in electric buses (29,200 particles/cm3). Median PM10 exposure was highest from diesel buses (47 μg/m3) and lowest along the high- and low-traffic bicycle routes (39 and 37 μg/m3). The median soot exposure was highest in gasoline-fueled cars (9.0 × 10−5/m), diesel cars (7.9 × 10−5/m), and diesel buses (7.4 × 10−5/m) and lowest along the low-traffic bicycle route (4.9 × 10−5/m). Because the minute ventilation (volume of air per minute) of cyclists, which we estimated from measured heart rates, was twice the minute ventilation of car and bus passengers, we calculated that the inhaled air pollution doses were highest for cyclists. With the exception of PM10, we found that inhaled air pollution doses were lowest for electric bus passengers. Conclusions Commuters’ rush hour exposures were significantly influenced by mode of transport, route, and fuel type. PMID:20185385

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 1. The Russell-Muller debate

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper assesses the discovery of the dose-rate effect in radiation genetics and how it challenged fundamental tenets of the linear non-threshold (LNT) dose response model, including the assumptions that all mutational damage is cumulative and irreversible and that the dose-response is linear at low doses. Newly uncovered historical information also describes how a key 1964 report by the International Commission for Radiological Protection (ICRP) addressed the effects of dose rate in the assessment of genetic risk. This unique story involves assessments by two leading radiation geneticists, Hermann J. Muller and William L. Russell, who independently argued that the report'smore » Genetic Summary Section on dose rate was incorrect while simultaneously offering vastly different views as to what the report's summary should have contained. This paper reveals occurrences of scientific disagreements, how conflicts were resolved, which view(s) prevailed and why. During this process the Nobel Laureate, Muller, provided incorrect information to the ICRP in what appears to have been an attempt to manipulate the decision-making process and to prevent the dose-rate concept from being adopted into risk assessment practices. - Highlights: • The discovery of radiation dose rate challenged the scientific basis of LNT. • Radiation dose rate occurred in males and females. • The dose rate concept supported a threshold dose-response for radiation.« less

75 FR 40729 - Residues of Quaternary Ammonium Compounds, N-Alkyl (C12-14

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

.... Systemic toxicity occurs after absorption and distribution of the chemical to tissues in the body. Such... identified (the LOAEL) or a Benchmark Dose (BMD) approach is sometimes used for risk assessment. Uncertainty.... No systemic effects observed up to 20 mg/ kg/day, highest dose of technical that could be tested...

Radiation dose optimization in pediatric temporal bone computed tomography: influence of tube tension on image contrast and image quality.

PubMed

Nauer, Claude Bertrand; Zubler, Christoph; Weisstanner, Christian; Stieger, Christof; Senn, Pascal; Arnold, Andreas

2012-03-01

The purpose of this experimental study was to investigate the effect of tube tension reduction on image contrast and image quality in pediatric temporal bone computed tomography (CT). Seven lamb heads with infant-equivalent sizes were scanned repeatedly, using four tube tensions from 140 to 80 kV while the CT-Dose Index (CTDI) was held constant. Scanning was repeated with four CTDI values from 30 to 3 mGy. Image contrast was calculated for the middle ear as the Hounsfield unit (HU) difference between bone and air and for the inner ear as the HU difference between bone and fluid. The influence of tube tension on high-contrast detail delineation was evaluated using a phantom. The subjective image quality of eight middle and inner ear structures was assessed using a 4-point scale (scores 1-2 = insufficient; scores 3-4 = sufficient). Middle and inner ear contrast showed a near linear increase with tube tension reduction (r = -0.94/-0.88) and was highest at 80 kV. Tube tension had no influence on spatial resolution. Subjective image quality analysis showed significantly better scoring at lower tube tensions, with highest image quality at 80 kV. However, image quality improvement was most relevant for low-dose scans. Image contrast in the temporal bone is significantly higher at low tube tensions, leading to a better subjective image quality. Highest contrast and best quality were found at 80 kV. This image quality improvement might be utilized to further reduce the radiation dose in pediatric low-dose CT protocols.

Comparison of parameters affecting GNP-loaded choroidal melanoma dosimetry; Monte Carlo study

NASA Astrophysics Data System (ADS)

Sharabiani, Marjan; Asadi, Somayeh; Barghi, Amir Rahnamai; Vaezzadeh, Mehdi

2018-04-01

The current study reports the results of tumor dosimetry in the presence of gold nanoparticles (GNPs) with different sizes and concentrations. Due to limited number of works carried out on the brachytherapy of choroidal melanoma in combination with GNPs, this study was performed to determine the optimum size and concentration for GNPs which contributes the highest dose deposition in tumor region, using two phantom test cases namely water phantom and a full Monte Carlo model of human eye. Both water and human eye phantoms were simulated with MCNP5 code. Tumor dosimetry was performed for a typical point photon source with an energy of 0.38 MeV as a high energy source and 103Pd brachytherapy source with an average energy of 0.021 MeV as a low energy source in water phantom and eye phantom respectively. Such a dosimetry was done for different sizes and concentrations of GNPs. For all of the diameters, increase in concentration of GNPs resulted in an increase in dose deposited in the region of interest. In a certain concentration, GNPs with larger diameters contributed more dose to the tumor region, which was more pronounced using eye phantom. 100 nm was reported as the optimum size in order to achieve the highest energy deposition within the target. This work investigated the optimum parameters affecting macroscopic dose enhancement in GNP-aided brachytherapy of choroidal melanoma. The current work also had implications on using low energy photon sources in the presence of GNPs to acquire the highest dose enhancement. This study is conducted through four different sizes and concentrations of GNPs. Considering the sensitivity of human eye tissue, in order to report the precise optimum parameters affecting radiosensitivity, a comprehensive study on a wide range of sizes and concentrations are required.

Determination of (210)Po in calcium supplements and the possible related dose assessment to the consumers.

PubMed

Strumińska-Parulska, Dagmara I

2015-12-01

The aim of this pioneer study was to investigate the most popular calcium supplements as a potential additional source of polonium (210)Po in human diet. The analyzed calcium pharmaceutics contained organic or inorganic calcium compounds; some from natural sources as mussels' shells, fish extracts, or sedimentary rocks. The objectives of this research were to investigate the naturally occurring (210)Po activity concentrations in calcium supplements, find the correlations between (210)Po concentration in medicament and calcium chemical form, and calculate the effective radiation dose connected to analyzed calcium supplement consumption. As results showed, (210)Po concentrations in natural origin calcium supplements (especially sedimentary rocks) were higher than the other analyzed. Also the results of (210)Po analysis obtained for inorganic forms of calcium supplements were higher. The highest (210)Po activity concentrations were determined in mineral tablets made from sedimentary rocks: dolomite and chalk - 3.88 ± 0.22 and 3.36 ± 0.10 mBq g(-1) respectively; while the lowest in organic calcium compounds: calcium lactate and calcium gluconate - 0.07 ± 0.02 and 0.17 ± 0.01 mBq g(-1). The annual effective radiation doses from supplements intake were estimated as well. The highest annual radiation dose from (210)Po taken with 1 tablet of calcium supplement per day was connected to sample made from chalk - 2.5 ± 0.07 μSv year(-1), while the highest annual radiation dose from (210)Po taken with 1 g of pure calcium per day was connected to dolomite - 12.7 ± 0.70 μSv year(-1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of gamma irradiation on the microbiological quality and on the functional properties of proteins in dry red kidney beans ( Phaseolus vulgaris)

NASA Astrophysics Data System (ADS)

Dogbevi, M. K.; Vachon, C.; Lacroix, M.

2000-03-01

Gamma-irradiation was found to affect the physicochemical properties of dry red kidney beans. The highest dose used (8 kGy) significantly ( P⩽0.05) modified the extent of deamidation, the number of sulfhydryl groups, as well as the solubility and the hydrophobicity of the protein. Deamidation, protein solubility and hydrophobicity all increased with the irradiation dose while the number of sulfhydryl groups was reduced by the treatment. Furthermore, irradiation also affected the outgrowth of natural filamentous fungi contaminants present on the dry beans. A dose of 1.5 kGy reduced the number of filamentous fungi by 2 log cycles immediately after treatment. However, the highest dose used (3 kGy) did not eliminate the filamentous fungi completely. Moreover, the filamentous fungi population was a lot less diversified on the irradiated samples. Species of Aspergillus sp. and Penicillium sp. were more abundant on the unirradiated beans while the beans irradiated at 3 kGy contained were predominantly infected by species of Rhizopus sp. , Cladosporium sp. and Alternaria sp.

Early-stage central lung cancer and volumetric modulated arc therapy: a dosimetric case study with literature review.

PubMed

Valakh, Vladimir; Chan, Philip; D'Adamo, Karen; Micaily, Bizhan

2013-10-01

In the present article we review on the use of Volumetric Modulated Arc Therapy (VMAT) for a small lung nodule that was centrally located in close proximity to the mediastinal structures. An inoperable patient with central, clinical stage IA adenocarcinoma of the right lung was treated with external-beam radiation therapy of 52.5 Gy in 15 factions. A single 360° coplanar arc VMAT plan (360-VMAT) was used for treatment and compared to step-and-shoot Intensity Modulation Radiotherapy (IMRT) and a single 180° ipsilateral partial arc VMAT plan (180-VMAT). Planning Target Volume (PTV) coverage was not different, and 360-VMAT had the highest dose homogeneity. Both 360-VMAT and 180-VMAT reduced esophageal dose compared to IMRT. While IMRT had the lowest lung dose, all 3 plans achieved acceptable sparing of the lung. 180-VMAT had the highest dose conformity. Both 360-VMAT and 180-VMAT improved esophageal sparing compared to IMRT. Use of VMAT in early-stage, centrally located NSCLC is a promising treatment approach and merits additional investigation.

Estimated human absorbed dose of a new (153)Sm bone seeking agent based on biodistribution data in mice: Comparison with (153)Sm-EDTMP.

PubMed

Yousefnia, Hassan; Zolghadri, Samaneh

2015-11-01

The main goal in radiotherapy is to deliver the absorbed dose within the target organs in highest possible amount, while the absorbed dose of the other organs, especially the critical organs, should be kept as low as possible. In this work, the absorbed dose to human organs for a new (153)Sm bone-seeking agent was investigated. (153)Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid ((153)Sm-BPAMD) complex was successfully prepared. The biodistribution of the complex was investigated in male Syrian mice up to 48 h post injection. The human absorbed dose of the complex was estimated based on the biodistribution data of the mice by radiation absorbed dose assessment resource (RADAR) method. The target to non-target absorbed dose ratios for (153)Sm-BPAMD were compared with these ratios for (153)Sm-EDTMP. The highest absorbed dose for (153)Sm-BPAMD was observed in bone surface with 5.828 mGy/MBq. The dose ratios of the bone surface to the red marrow and to the total body for (153)Sm-BPAMD were 5.3 and 20.0, respectively, while these ratios for (153)Sm-EDTMP were 4.4 and 18.3, respectively. This means, for a given dose to the bone surface as the target organ, the red marrow (as the main critical organ) and the total body would receive lesser absorbed dose in the case of (153)Sm-BPAMD. Generally, the human absorbed dose estimation of (153)Sm-BPAMD indicated that all other tissues approximately received insignificant absorbed dose in comparison with bone surface and therefore can be regarded as a new potential agent for bone pain palliation therapy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-F-I-32: Organ Doses from Pediatric Head CT Scan

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

Liu, H; Liu, Q; Qiu, J

Purpose: To evaluate the organ doses of pediatric patients who undergoing head CT scan using Monte Carlo (MC) simulation and compare it with measurements in anthropomorphic child phantom.. Methods: A ten years old children voxel phantom was developed from CT images, the voxel size of the phantom was 2mm*2mm*2mm. Organ doses from head CT scan were simulated using MCNPX software, 180 detectors were placed in the voxel phantom to tally the doses of the represented tissues or organs. When performing the simulation, 120 kVp and 88 mA were selected as the scan parameters. The scan range covered from the topmore » of the head to the end of the chain, this protocol was used at CT simulator for radiotherapy. To validate the simulated results, organ doses were measured with radiophotoluminescence (RPL) detectors, placed in the 28 organs of the 10 years old CIRS ATOM phantom. Results: The organ doses results matched well between MC simulation and phantom measurements. The eyes dose was showed to be as expected the highest organ dose: 28.11 mGy by simulation and 27.34 mGy by measurement respectively. Doses for organs not included in the scan volume were much lower than those included in the scan volume, thymus doses were observed more than 10 mGy due the CT protocol for radiotherapy covered more body part than routine head CT scan. Conclusion: As the eyes are superficial organs, they may receive the highest radiation dose during the CT scan. Considering the relatively high radio sensitivity, using shielding material or organ based tube current modulation technique should be encouraged to reduce the eye radiation risks. Scan range was one of the most important factors that affects the organ doses during the CT scan. Use as short as reasonably possible scan range should be helpful to reduce the patient radiation dose. This work was supported by the National Natural Science Foundation of China(11475047)« less

Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler.

PubMed Central

Farr, S. J.; Rowe, A. M.; Rubsamen, R.; Taylor, G.

1995-01-01

BACKGROUND--Gamma scintigraphy was employed to assess the deposition of aerosols emitted from a pressurised metered dose inhaler (MDI) contained in a microprocessor controlled device (SmartMist), a system which analyses an inspiratory flow profile and automatically actuates the MDI when predefined conditions of flow rate and cumulative inspired volume coincide. METHODS--Micronised salbutamol particles contained in a commercial MDI (Ventolin) were labelled with 99m-technetium using a method validated by the determination of (1) aerosol size characteristics of the drug and radiotracer following actuation into an eight stage cascade impactor and (2) shot potencies of these non-volatile components as a function of actuation number. Using nine healthy volunteers in a randomised factorial interaction design the effect of inspiratory flow rate (slow, 30 l/min; medium, 90 l/min; fast, 270 l/min) combined with cumulative inspired volume (early, 300 ml; late, 3000 ml) was determined on total and regional aerosol lung deposition using the technique of gamma scintigraphy. RESULTS--The SmartMist firing at the medium/early setting (medium flow and early in the cumulative inspired volume) resulted in the highest lung deposition at 18.6 (1.42)%. The slow/early setting gave the second highest deposition at 14.1 (2.06)% with the fast/late setting resulting in the lowest (7.6 (1.15)%). Peripheral lung deposition obtained for the medium/early (9.1 (0.9)%) and slow/early (7.5 (1.06)%) settings were equivalent but higher than those obtained with the other treatments. This reflected the lower total lung deposition at these other settings as no difference in regional deposition, expressed as a volume corrected central zone:peripheral zone ratio, was apparent for all modes of inhalation studied. CONCLUSIONS--The SmartMist device allowed reproducible actuation of an MDI at a preprogrammed point during inspiration. The extent of aerosol deposition in the lung is affected by a change in firing point and is promoted by an inhaled flow rate of up to 90 l/min-that is, the slow and medium setting used in these studies. PMID:7638806

Modelling the Ozone-Based Treatments for Inactivation of Microorganisms

PubMed Central

Brodowska, Agnieszka Joanna; Nowak, Agnieszka; Kondratiuk-Janyska, Alina; Piątkowski, Marcin; Śmigielski, Krzysztof

2017-01-01

The paper presents the development of a model for ozone treatment in a dynamic bed of different microorganisms (Bacillus subtilis, B. cereus, B. pumilus, Escherichia coli, Pseudomonas fluorescens, Aspergillus niger, Eupenicillium cinnamopurpureum) on a heterogeneous matrix (juniper berries, cardamom seeds) initially treated with numerous ozone doses during various contact times was studied. Taking into account various microorganism susceptibility to ozone, it was of great importance to develop a sufficiently effective ozone dose to preserve food products using different strains based on the microbial model. For this purpose, we have chosen the Weibull model to describe the survival curves of different microorganisms. Based on the results of microorganism survival modelling after ozone treatment and considering the least susceptible strains to ozone, we selected the critical ones. Among tested strains, those from genus Bacillus were recognized as the most critical strains. In particular, B. subtilis and B. pumilus possessed the highest resistance to ozone treatment because the time needed to achieve the lowest level of its survival was the longest (up to 17.04 min and 16.89 min for B. pumilus reduction on juniper berry and cardamom seed matrix, respectively). Ozone treatment allow inactivate microorganisms to achieving lower survival rates by ozone dose (20.0 g O3/m3 O2, with a flow rate of 0.4 L/min) and contact time (up to 20 min). The results demonstrated that a linear correlation between parameters p and k in Weibull distribution, providing an opportunity to calculate a fitted equation of the process. PMID:28991199

A controlled investigation of propofol, thiopentone and methohexitone.

PubMed

Gold, M I; Abraham, E C; Herrington, C

1987-09-01

This was a randomized study of 180 ASA physical status I and II patients, 60 in each group who received propofol (PROP), 2.5 mg . kg-1, thiopentone (THIO), 4 mg . kg-1, or methohexitone (METH), 1.5 mg . kg-1. Control values, followed by changes after induction and during a 3-min delay before intubation were recorded for the following parameters: heart rate (HR), systolic and diastolic blood pressures (SBP, DBP), respiratory rate (RR), end-tidal CO2 (PETCO2), and induction time (IT). In addition, the incidence of adverse reactions and time for recovery from anaesthesia were noted. The IT (mean +/- SE) was 35 +/- 1 sec for propofol, 35 +/- 1.2 sec for thiopentone and 34 +/- 1.4 sec for methohexitone. Ninety-three per cent of the PROP group fell asleep with one dose and required no additional doses. Fifty per cent of each of the THIO and METH groups required additional agents (p less than 0.05). METH was associated with the highest elevation in HR, PROP the least (p less than 0.05). PROP was associated with the most decrease in SBP and DBP and in addition respiratory depression (p less than 0.05). The incidence of injection pain or excitatory activity was equal in the three groups with the exception that 14 patients who received METH developed hiccoughs while none did in the other groups. PROP was associated with the most rapid recovery, particularly with respect to the orientation time. We conclude that PROP is an effective alternative to barbiturate induction and that the published recommended doses of THIO and METH are often ineffective.

Reproduction of bobwhites fed different dietary concentrations of an organophosphate insecticide, methamidophos

USGS Publications Warehouse

Stromborg, K.L.

1986-01-01

Pairs of first-year breeding bobwhites were fed constant or variable concentrations of methamidophos for 15 days, or a control diet in a pair-fed design in which they were matched by body weights to pairs in the constant group. Treatments for the constant group were 5.0, 7.8, 12.3, 19.2, and 30.0 ppm for 5 pairs at each concentration. The number of pairs per concentration and peak concentrations for the variable pairs were identical to the constant dosages. Concentrations for the variable group were increased by a factor of four during two 3-day periods in order to reach the peak concentrations on days 7?9 after which they were decreased by 18% every 3 days to correspond to an environmental half-time of 10.5 days. Food consumption, egg production, hatchability of eggs under artificial incubation, and survival of hatched chicks for 2 weeks were recorded for each pair during 15-day treatment and 21-day posttreatment periods. Mortality was high in the highest constant dosage (2/10) and the associated pair-fed groups (3/10). Food consumption and egg production rates were negatively dose-related during the treatment period in the constant and variable groups. The laying rate of pair-fed hens was reduced to the same extent as in the constant group. Reproductive inhibition was not permanent and pairs resumed laying after a dose-related recovery interval. No dose-related effects on hatchability or chick survival were detected. Furthermore, there was no evidence of a pesticide effect on reproduction in addition to that exerted through pesticide-induced anorexia.

Development of a subunit vaccine for infectious pancreatic necrosis virus using a baculovirus insect/larvae system

USGS Publications Warehouse

Shivappa, R.B.; McAllister, P.E.; Edwards, G.H.; Santi, N.; Evensen, O.; Vakharia, V.N.; ,

2005-01-01

Various attempts to develop a vaccine against infectious pancreatic necrosis virus (IPNV) have not yielded consistent results. Thus, at present, no commercial vaccine is available that can be used with confidence to immunize fry of salmon and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp strain and expressed all structural protein genes in insect cells and larvae using a baculovirus expression system. Green fluorescent protein was also co-expressed as a reporter molecule. High yields of IPNV proteins were obtained and the structural proteins self assembled to form virus-like particles (VLPs). We tested the immunogenicity of the putative VLP antigen in immersion vaccine experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using an oil adjuvant formulation. Rainbow trout were challenged by immersion using either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination, while Atlantic salmon were bath challenged with Sp strain after two months, after parr-smolt transformation. In the rainbow trout fry challenged two weeks post-immunization, cumulative mortality rates three weeks post challenge were 14 % in the fry that had received the highest dose versus 8 % in the control groups. No indication of protection was seen in repeated trials using a lower dose of antigen and challenge three weeks post-immunisation. The cumulative mortality rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post challenge was lower (56 %) than in the control fish (77 %), showing a dose-response pattern.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes.

PubMed

Colombo, John; Jill Shaddy, D; Kerling, Elizabeth H; Gustafson, Kathleen M; Carlson, Susan E

2017-06-01

The DHA Intake and Measurement of Neural Development (DIAMOND) trial represents one of only a few studies of the long-term dose-response effects of LCPUFA-supplemented formula feeding during infancy. The trial contrasted the effects of four formulations: 0.00% docosahexaenoic acid (DHA)/0.00% arachidonic acid (ARA), 0.32% DHA/0.64% ARA, 0.64% DHA/0.64% ARA, and 0.96% DHA/0.64% ARA against a control condition (0.00% DHA/0.00% ARA). The results of this trial have been published elsewhere, and show improved cognitive outcomes for infants fed supplemented formulas, but a common finding among many of the outcomes show a reduction of benefit for the highest DHA dose (i.e., 0.96%DHA/0.64% ARA, that is, a DHA: ARA ratio 1.5:1.0). The current paper gathers and summarizes the evidence for the reduction of benefit at this dose, and in an attempt to account for this reduced benefit, presents for the first time data from infants' red blood cell (RBC) assays taken at 4 and 12 months of age. Those assays indicate that blood DHA levels generally rose with increased DHA supplementation, although those levels tended to plateau as the DHA-supplemented level exceeded 0.64%. Perhaps more importantly, ARA levels showed a strong inverted-U function in response to increased DHA supplementation; indeed, infants assigned to the formula with the highest dose of DHA (and highest DHA/ARA ratio) showed a reduction in blood ARA relative to more intermediate DHA doses. This finding raises the possibility that reduced ARA may be responsible for the reduction in benefit on cognitive outcomes seen at this dose. The findings implicate the DHA/ARA balance as an important variable in the contribution of LCPUFAs to cognitive and behavioral development in infancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of the Revised 10 CFR 835 on the Neutron Dose Rates at LLNL

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

Radev, R

2009-01-13

In June 2007, 10 CFR 835 [1] was revised to include new radiation weighting factors for neutrons, updated dosimetric models, and dose terms consistent with the newer ICRP recommendations. A significant aspect of the revised 10 CFR 835 is the adoption of the recommendations outlined in ICRP-60 [2]. The recommended new quantities demand a review of much of the basic data used in protection against exposure to sources of ionizing radiation. The International Commission on Radiation Units and Measurements has defined a number of quantities for use in personnel and area monitoring [3,4,5] including the ambient dose equivalent H*(d) tomore » be used for area monitoring and instrument calibrations. These quantities are used in ICRP-60 and ICRP-74. This report deals only with the changes in the ambient dose equivalent and ambient dose rate equivalent for neutrons as a result of the implementation of the revised 10 CFR 835. In the report, the terms neutron dose and neutron dose rate will be used for convenience for ambient neutron dose and ambient neutron dose rate unless otherwise stated. This report provides a qualitative and quantitative estimate of how much the neutron dose rates at LLNL will change with the implementation of the revised 10 CFR 835. Neutron spectra and dose rates from selected locations at the LLNL were measured with a high resolution spectroscopic neutron dose rate system (ROSPEC) as well as with a standard neutron rem meter (a.k.a., a remball). The spectra obtained at these locations compare well with the spectra from the Radiation Calibration Laboratory's (RCL) bare californium source that is currently used to calibrate neutron dose rate instruments. The measurements obtained from the high resolution neutron spectrometer and dose meter ROSPEC and the NRD dose meter compare within the range of {+-}25%. When the new radiation weighting factors are adopted with the implementation of the revised 10 CFR 835, the measured dose rates will increase by up to 22%. The health physicists should consider this increase for any areas that have dose rates near a posting limit, such as near the 100 mrem/hr for a high radiation area, as this increase in measured dose rate may result in some changes to postings and consequent radiological controls.« less

The influence of lifestyle on airborne particle surface area doses received by different Western populations.

PubMed

Pacitto, A; Stabile, L; Moreno, T; Kumar, P; Wierzbicka, A; Morawska, L; Buonanno, G

2018-01-01

In the present study, the daily dose in terms of particle surface area received by citizens living in five cities in Western countries, characterized by different lifestyle, culture, climate and built-up environment, was evaluated and compared. For this purpose, the exposure to sub-micron particle concentration levels of the population living in Barcelona (Spain), Cassino (Italy), Guilford (United Kingdom), Lund (Sweden), and Brisbane (Australia) was measured through a direct exposure assessment approach. In particular, measurements of the exposure at a personal scale were performed by volunteers (15 per each population) that used a personal particle counter for different days in order to obtain exposure data in microenvironments/activities they resided/performed. Non-smoking volunteers performing non-industrial jobs were considered in the study. Particle concentration data allowed obtaining the exposure of the population living in each city. Such data were combined in a Monte Carlo method with the time activity pattern data characteristics of each population and inhalation rate to obtain the most probable daily dose in term of particle surface area as a function of the population gender, age, and nationality. The highest daily dose was estimated for citizens living in Cassino and Guilford (>1000 mm 2 ), whereas the lowest value was recognized for Lund citizens (around 100 mm 2 ). Indoor air quality, and in particular cooking and eating activities, was recognized as the main influencing factor in terms of exposure (and thus dose) of the population: then confirming that lifestyle (e.g. time spent in cooking activities) strongly affect the daily dose of the population. On the contrary, a minor or negligible contribution of the outdoor microenvironments was documented. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potential of UVC germicidal irradiation in suppressing crown rot disease, retaining postharvest quality and antioxidant capacity of Musa AAA "Berangan" during fruit ripening.

PubMed

S Mohamed, Nuratika Tamimi; Ding, Phebe; Kadir, Jugah; M Ghazali, Hasanah

2017-09-01

Crown rot caused by fungal pathogen is the most prevalent postharvest disease in banana fruit that results significant economic losses during transportation, storage, and ripening period. Antifungal effects of ultraviolet C (UVC) irradiation at doses varied from 0.01 to 0.30 kJ m -2 were investigated in controlling postharvest crown rot disease, maintenance of fruit quality, and the effects on antioxidant capacity of Berangan banana fruit during ripening days at 25 ± 2°C and 85% RH. Fruits irradiated with 0.30 kJ m -2 exhibited the highest (i.e., 62.51%) reduction in disease severity. However, the application of UVC at all doses caused significant browning damages on fruit peel except the dose of 0.01 kJ m -2 . This dose synergistically reduced 46.25% development of postharvest crown and did not give adverse effects on respiration rate, ethylene production, weight loss, firmness, color changes, soluble solids concentration, titratable acidity, and pH in banana as compared to the other treatments and control. Meanwhile, the dose also enhanced a significant higher level of total phenolic content, FRAP, and DPPH values than in control fruits indicating the beneficial impact of UVC in fruit nutritional quality. The results of scanning electron micrographs confirmed that UVC irradiation retarded the losses of wall compartments, thereby maintained the cell wall integrity in the crown tissue of banana fruit. The results suggest that using 0.01 kJ m -2 UVC irradiation dose as postharvest physical treatment, the crown rot disease has potential to be controlled effectively together with maintaining quality and antioxidant of banana fruit.

3,3′,4,4′,5-Pentachlorobiphenyl (PCB 126) Decreases Hepatic and Systemic Ratios of Epoxide to Diol Metabolites of Unsaturated Fatty Acids in Male Rats

PubMed Central

Wu, Xianai; Yang, Jun; Morisseau, Christophe; Robertson, Larry W.; Hammock, Bruce; Lehmler, Hans-Joachim

2016-01-01

Disruption of the homeostasis of oxygenated regulatory lipid mediators (oxylipins), potential markers of exposure to aryl hydrocarbon receptor (AhR) agonists, such as 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), is associated with a range of diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Here we test the hypothesis that PCB 126 exposure alters the levels of oxylipins in rats. Male Sprague-Dawley rats (5-weeks old) were treated over a 3-month period every 2 weeks with intraperitoneal injections of PCB 126 in corn oil (cumulative doses of 0, 19.8, 97.8, and 390 µg/kg b.w.; 6 injections total). PCB 126 treatment caused a reduction in growth rates at the highest dose investigated, a dose-dependent decrease in thymus weights, and a dose-dependent increase in liver weights. Liver PCB 126 levels increased in a dose-dependent manner, while levels in plasma were below or close to the detection limit. The ratios of several epoxides to diol metabolites formed via the cytochrome P450 (P450) monooxygenase/soluble epoxide hydrolase (sEH) pathway from polyunsaturated fatty acids displayed a dose-dependent decrease in the liver and plasma, whereas levels of oxylipins formed by other metabolic pathways were generally not altered by PCB 126 treatment. The effects of PCB 126 on epoxide-to-diol ratios were associated with an increased CYP1A activity in liver microsomes and an increased sEH activity in liver cytosol and peroxisomes. These results suggest that oxylipins are potential biomarkers of exposure to PCB 126 and that the P450/sEH pathway is a therapeutic target for PCB 126-mediated hepatotoxicity that warrants further attention. PMID:27208083

What is the best approach to tailoring hydrocortisone dose to meet patient needs in 2012?

PubMed

Debono, Miguel; Ross, Richard J

2013-05-01

Cortisol is an essential stress hormone and replacement with oral hydrocortisone is lifesaving in patients with adrenal insufficiency. Cortisol has a diurnal rhythm regulated by the central body clock and this rhythm is a metabolic signal for peripheral tissue clocks. Loss of cortisol rhythmicity is associated with fatigue, depression and insulin resistance. A general principle in endocrinology is to replace hormones to replicate physiological concentrations; however, the pharmacokinetics of oral immediate-release hydrocortisone make it impossible to fully mimic the cortisol rhythm and patients still have an increased morbidity and mortality despite replacement. Traditionally, physicians have replaced hydrocortisone with a total daily dose based on the diurnal 24-h cortisol production rate with hydrocortisone given twice or thrice daily, with the highest dose first thing in the morning. Monitoring treatment and dose titration has been much debated with some clinicians using cortisol day curves and others relying on clinical symptoms. The main challenge is that there is no established biomarker of cortisol activity. In addressing the clinical question, we have taken the view that an understanding of the cortisol circadian rhythm and hydrocortisone pharmacokinetics is essential when tailoring hydrocortisone dose. Using this approach, we have developed a thrice daily, weight-related, dosing regimen and a pharmacokinetic and clinical method to monitor treatment. Our argument for replicating the cortisol circadian rhythm is based on the observation that disruption of the rhythm is associated with ill health, and the few studies that have compared different treatment regimens. Further studies are required to definitively test the benefits of replacing the cortisol circadian rhythm in patients with adrenal insufficiency. © 2012 Blackwell Publishing Ltd.

Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans.

PubMed

Maqueda, Ana Elda; Valle, Marta; Addy, Peter H; Antonijoan, Rosa Maria; Puntes, Montserrat; Coimbra, Jimena; Ballester, Maria Rosa; Garrido, Maite; González, Mireia; Claramunt, Judit; Barker, Steven; Johnson, Matthew W; Griffiths, Roland R; Riba, Jordi

2015-06-05

Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedelic-like changes in perception, but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profiles of subjective effects of increasing doses of salvinorin-A in healthy volunteers, with a special emphasis on interoception. A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included, among others, the Hallucinogen Rating Scale, the Altered States of Consciousness, and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness. Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the highest dose led to a sense of a complete loss of contact with the body. Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audio-visual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception, and the sense of body ownership in humans. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

The estimation of galactic cosmic ray penetration and dose rates

NASA Technical Reports Server (NTRS)

Burrell, M. O.; Wright, J. J.

1972-01-01

This study is concerned with approximation methods that can be readily applied to estimate the absorbed dose rate from cosmic rays in rads - tissue or rems inside simple geometries of aluminum. The present work is limited to finding the dose rate at the center of spherical shells or behind plane slabs. The dose rate is calculated at tissue-point detectors or for thin layers of tissue. This study considers cosmic-rays dose rates for both free-space and earth-orbiting missions.

The Prevalence of PCR-Confirmed Pertussis Cases in Palestine From Archived Nasopharyngeal Samples.

PubMed

Dumaidi, Kamal; Al-Jawabreh, Amer

2018-05-01

Pertussis caused by Bordetella pertussis is a vaccine-preventable disease causing whooping cough in humans of all ages. This study reports infection rate of pertussis in Palestine between the years 2004-2008 from archived nasopharyngeal samples collected from clinically- suspected cases. A convenience archived DNA samples collected from 267 clinically-suspected pertussis cases were investigated for B. pertussis. Laboratory diagnosis was done by examining all DNA samples using polymerase chain reaction (PCR). Approximately 49% (130/267) were confirmed by PCR. A pertussis peak was shown to occur in 2008 with 77% (100/130) of PCR-confirmed cases isolated in that year. PCR-confirmed cases existed in all Palestinian districts with highest rate in Ramallah, Bethlehem, Jenin and Al-Khalil. Half of the PCR-confirmed cases (68/130) were less than 2 months old. The positivity rate among who had three doses of vaccine (at 2, 4 and 6 months) was 38%, and became 50% with the fourth dose at 12 months. The prevalence of pertussis was found to be significantly high among infants less than 2 months old. Active pertussis surveillance using rapid PCR assays is essential, as it is helpful in prompt diagnosis and treatment of patients with pertussis. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Heat Tolerance and the Peripheral Effects of Anticholinergics

DTIC Science & Technology

1988-01-30

0c. GENDER: Responses of 27 males and 12 females showed that both SR and AGD increased as a function of log MCh dose. SR was affected by gender only...at the 2 highest doses ( male SR slightly greater). At all but the lowest dose AGD was significantly greater for females. ACCLIMATION: Responses of 6... males to MCh were measured before and after 20. DISTRIBUTION /AVAILABILITY OF ABSTRACT 21. ABSTRACT SECURITY CLASSIFICATION 0 UNCLASSIFIED/UNLIMITED 0

Estimation of ambient dose equivalent distribution in the 18F-FDG administration room using Monte Carlo simulation.

PubMed

Nagamine, Shuji; Fujibuchi, Toshioh; Umezu, Yoshiyuki; Himuro, Kazuhiko; Awamoto, Shinichi; Tsutsui, Yuji; Nakamura, Yasuhiko

2017-03-01

In this study, we estimated the ambient dose equivalent rate (hereafter "dose rate") in the fluoro-2-deoxy-D-glucose (FDG) administration room in our hospital using Monte Carlo simulations, and examined the appropriate medical-personnel locations and a shielding method to reduce the dose rate during FDG injection using a lead glass shield. The line source was assumed to be the FDG feed tube and the patient a cube source. The dose rate distribution was calculated with a composite source that combines the line and cube sources. The dose rate distribution was also calculated when a lead glass shield was placed in the rear section of the lead-acrylic shield. The dose rate behind the automatic administration device decreased by 87 % with respect to that behind the lead-acrylic shield. Upon positioning a 2.8-cm-thick lead glass shield, the dose rate behind the lead-acrylic shield decreased by 67 %.

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

DOE PAGES

Hiller, Mauritius; Dewji, Shaheen Azim

2017-02-16

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

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

Hiller, Mauritius; Dewji, Shaheen Azim

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

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

Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher

2014-07-01

Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% ofmore » patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.« less

High-level dietary cadmium exposure is associated with global DNA hypermethylation in the gastropod hepatopancreas

PubMed Central

Popescu, Cristina; Draghici, George A.; Andrica, Florina-Maria; Privistirescu, Ionela A.; Gergen, Iosif I.; Stöger, Reinhard

2017-01-01

5-methylcytosine (5mC) is a key epigenetic mark which influences gene expression and phenotype. In vertebrates, this epigenetic mark is sensitive to Cd exposure, but there is no information linking such an event with changes in global 5mC levels in terrestrial gastropods despite their importance as excellentecotoxicological bioindicators of metal contamination. Therefore, we first evaluated total 5mC content in DNA of the hepatopancreas of adult Cantareus aspersus with the aim to determine whether this epigenetic mark is responsive to Cd exposure. The experiment was conducted under laboratory conditions and involved a continuous exposure, multiple dose- and time-point (14, 28, and 56 days) study design. Hepatopancreas cadmium levels were measured using Flame Atomic Absorption Spectrometry and the percentage of 5-mC in samples using an ELISA-based colorimetric assay. Snail death rates were also assessed. Our results, for the first time, reveal the presence of 5mC in C. aspersus and provide evidence for Cd-induced changes in global 5mC levels in DNA of gastropods and mollusks. Although less sensitive than tissue accumulation, DNA methylation levels responded in a dose- and time-dependent manner to dietary cadmium, with exposure dose having a much stronger effect than exposure duration. An obvious trend of increasing 5mC levels was observed starting at 28 days of exposure to the second highest dose and this trend persisted at the two highest treatments for close to one month, when the experiment was terminated after 56 days. Moreover, a strong association was identified between Cd concentrations in the hepatopancreas and DNA methylation levels in this organ. These data indicate an overall trend towards DNA hypermethylation with elevated Cd exposure. No consistent lethal effect was observed, irrespective of time point and Cd-dosage. Overall, our findings suggest that the total 5mC content in DNA of the hepatopancreas of land snails is responsive to sublethal Cd exposure and give new insights into invertebrate environmental epigenetics. PMID:28877233

Motion Interplay as a Function of Patient Parameters and Spot Size in Spot Scanning Proton Therapy for Lung Cancer

PubMed Central

Grassberger, Clemens; Dowdell, Stephen; Lomax, Antony; Sharp, Greg; Shackleford, James; Choi, Noah; Willers, Henning; Paganetti, Harald

2013-01-01

Purpose Quantify the impact of respiratory motion on the treatment of lung tumors with spot scanning proton therapy. Methods and Materials 4D Monte Carlo simulations were used to assess the interplay effect, which results from relative motion of the tumor and the proton beam, on the dose distribution in the patient. Ten patients with varying tumor sizes (2.6-82.3cc) and motion amplitudes (3-30mm) were included in the study. We investigated the impact of the spot size, which varies between proton facilities, and studied single fractions and conventionally fractionated treatments. The following metrics were used in the analysis: minimum/maximum/mean dose, target dose homogeneity and 2-year local control rate (2y-LC). Results Respiratory motion reduces the target dose homogeneity, with the largest effects observed for the highest motion amplitudes. Smaller spot sizes (σ≈3mm) are inherently more sensitive to motion, decreasing target dose homogeneity on average by a factor ~2.8 compared to a larger spot size (σ≈13mm). Using a smaller spot size to treat a tumor with 30mm motion amplitude reduces the minimum dose to 44.7% of the prescribed dose, decreasing modeled 2y-LC from 87.0% to 2.7%, assuming a single fraction. Conventional fractionation partly mitigates this reduction, yielding a 2y-LC of 71.6%. For the large spot size, conventional fractionation increases target dose homogeneity and prevents a deterioration of 2y-LC for all patients. No correlation with tumor volume is observed. The effect on the normal lung dose distribution is minimal: observed changes in mean lung dose and lung V20 are <0.6Gy(RBE) and <1.7% respectively. Conclusions For the patients in this study, 2y-LC could be preserved in the presence of interplay using a large spot size and conventional fractionation. For treatments employing smaller spot sizes and/or in the delivery of single fractions, interplay effects can lead to significant deterioration of the dose distribution and lower 2y-LC. PMID:23462423

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

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

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

2014-08-15

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

Acute changes in the central nervous system of monkeys exposed to protons.

NASA Technical Reports Server (NTRS)

Haymaker, W.; Ibrahim, M. Z. M.; Miquel, J.; Call, N.; Noden, P.; Ashley, W.; Ballinger, E. R.; Ghidoni, J.; Lindsay, I. R.; Behar, A. J.

1972-01-01

Study of the changes occurring in simian brain exposed to protons of varied energy, given in wide dose and dose-rate ranges. Results show that inflammatory reaction and glycogen accumulation in astrocytes occurred practically in all animals. Cerebral cortical necrosis, granule cell pyknosis, and inflammatory reaction occurred at doses far lower than effective for high-energy gamma radiation given other series of monkeys at comparable dose rates. Metallic impregnation, carried out in virtually all the animals tested, revealed a wide variation in glial response even at equal doses and dose rates in the same proton energy series. Proton energy effect, dose effect, dose-time effect, and dose-rate effect were evident in the various morphological categories investigated, but inconsistencies were encountered.

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

NASA Technical Reports Server (NTRS)

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

1989-01-01

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

Effects of long-term corticosterone implants on growth and immune function in juvenile alligators, Alligator mississippiensis.

PubMed

Morici, L A; Elsey, R M; Lance, V A

1997-10-01

Sixty juvenile alligators were implanted subcutaneously with slow release pellets of corticosterone or placebo. Alligators were divided into five different groups such that each group received a different dose. A blood sample was taken prior to and 4 days after the implants were in place to measure hormone levels. Additional blood samples were collected at 1 month and 3 months. At 4 days corticosterone levels ranged from 3,400 ng/ml in the group treated with the high dose to 40 ng/ml in the group implanted with the low dose. The extremely high dose caused 40% mortality within 4 weeks. It was evident that the pellets did not release the hormone for the expected 90 days. Circulating levels of corticosterone were back to baseline levels by 3 months. Hormone levels achieved at 4 days were a reliable predictor of subsequent growth. Rate of growth was negatively correlated with plasma corticosterone at 4 days (r2 = 0.711) and at 1 month (r2 = 0.544) posttreatment. Differential white blood cell counts performed after 1 month of treatment showed a clear effect of the implant. Alligators treated with corticosterone had decreased percentages of lymphocytes, eosinophils, and basophils and had a higher heterophil/lymphocyte (H/L) ratio than the placebo group. Furthermore, histological examination of the spleen revealed a significant depletion of lymphoid cells in alligators treated with the highest dose of hormone. The results from this study demonstrate that exogenous corticosterone can mimic the effects of prolonged stress in juvenile alligators.

Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.

PubMed

Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T; Baumann, Heinz; Bellnier, David A; Sunar, Ulas; Tracy, Erin C; Rohrbach, Daniel J; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W

2013-12-01

The primary objective was to evaluate safety of 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Patients with histologically proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3 were assessed as potential indicators of PDT effective reaction. Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses. HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction. ©2013 AACR.

Capstone Depleted Uranium Aerosol Biokinetics, Concentrations, and Doses

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

Guilmette, Raymond A.; Miller, Guthrie; Parkhurst, MaryAnn

2009-02-26

One of the principal goals of the Capstone Depleted Uranium (DU) Aerosol Study was to quantify and characterize DU aerosols generated inside armored vehicles by perforation with a DU penetrator. This study consequently produced a database in which the DU aerosol source terms were specified both physically and chemically for a variety of penetrator-impact geometries and conditions. These source terms were used to calculate radiation doses and uranium concentrations for various scenarios as part of the Capstone DU Human Health Risk Assessment (HHRA). This paper describes the scenario-related biokinetics of uranium, and summarizes intakes, chemical concentrations to the organs, andmore » E(50) and HT(50) for organs and tissues based on exposure scenarios for personnel in vehicles at the time of perforation as well as for first responders. For a given exposure scenario (duration time and breathing rates), the range of DU intakes among the target vehicles and shots was not large, about a factor of 10, with the lowest being from a ventilated operational Abrams tank and the highest being for an unventilated Abrams with DU penetrator perforating DU armor. The ranges of committed effective doses were more scenario-dependent than were intakes. For example, the largest range, a factor of 20, was shown for scenario A, a 1-min exposure, whereas, the range was only a factor of two for the first-responder scenario (E). In general, the committed effective doses were found to be in the tens of mSv. The risks ascribed to these doses are discussed separately.« less

Impact of organic polyelectrolytes on coagulation of source-separated black water.

PubMed

Kozminykh, Pavlo; Heistad, Arve; Ratnaweera, Harsha C; Todt, Daniel

2016-01-01

Household wastewater is originated from common people's activities and has a potential harmful impact on the environment if discharged directly without proper treatment. Toilet wastewater or black water (BW) contains urine, faeces, toilet paper and flushing water and it contains the majority of pollutants obtained from a single household. In this study, the focus was on BW treatment using chemical methods. The main goal of current research was to define the possibility and applicability of conventional coagulants and flocculants in direct chemical treatment of vacuum-collected BW to remove particles, organic matter and phosphorous. After the definition of dosing ranges, based on the equivalent doses in conventional municipal and industrial wastewater treatment data, aluminium and iron coagulants, organic polyelectrolytes (polymers with anionic, neutral and cationic charge with different molecular weights) and their various combinations were tested using the well-known jar-test laboratory method to study aggregation and solid-liquid separation processes in raw BW. The most important process parameter during the coagulation was pH level, dependent on the type and doses of metal salts. Some side processes were found to occur while using iron-based coagulants. Dosing of either single coagulants or single polymers did not give satisfactory results, while a combination of aluminium salts and cationic polymers showed high removal rates in total suspended solids, total chemical oxygen demand and ortho-phosphates, reaching 97.8%, 92% and 98.6%, respectively, with the optimal doses of chemicals. Cationic polymers with the lowest molecular weight and highest charge density were the most efficient in combination with aluminium coagulants.

Higher parity is associated with increased risk of Type 2 diabetes mellitus in women: A linear dose-response meta-analysis of cohort studies.

PubMed

Guo, Peng; Zhou, Quan; Ren, Lei; Chen, Yu; Hui, Yue

2017-01-01

The goal of this study is to investigate the association between higher parity and the risk of occurrence of type 2 diabetes mellitus (T2DM) in women and to quantify the potential dose-response relation. We searched MEDLINE, and EMBASE electronic databases for related cohort studies up to March 10th, 2016. Summary rate ratios (RRs) and 95% confidence intervals (CIs) for T2DM with at least 3 categories of exposure were eligible. A random-effects dose-response analysis procedure was used to study the relations between them. After screening a total of 13,647 published studies, only 7 cohort studies (9,394 incident cases and 286,840 female participants) were found to be eligible for this meta-analysis. In the category analysis, the pooled RR for the highest number of parity vs. the lowest one was 1.42 (95% CI: 1.17-1.72, I 2 =71.5%, P heterogeneity =0.002, Power=0.99). In the dose-response analysis, a noticeable linear dose-risk relation was found between parity and T2DM (P for nonlinearity test =0.942). For every live birth increase in parity, the combined RR was 1.06 (95% CI: 1.02-1.09, I 2 =84.3%, P heterogeneity =0.003, Power=0.99). Subgroup and sensitivity analyses yielded similar results. No publication bias was found in the results. This meta-analysis suggests that higher parity and the risk of T2DM show a linear relationship in women. Copyright © 2017 Elsevier Inc. All rights reserved.

Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system

PubMed Central

Li, Gaowen; Ruan, Lina; Chen, Ruijie; Wang, Renye; Xie, Xupei; Zhang, Meixi; Chen, Lichao; Yan, Qizhi; Reed, Miranda; Chen, Jiechun; Xu, Ying; Pan, Jianchun; Huang, Wu

2016-01-01

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects. PMID:26220010

SU-F-T-349: Dosimetric Comparison of Three Different Simultaneous Integrated Boost Irradiation Techniques for Multiple Brain Metastases: Intensity-Modulatedradiotherapy, Hybrid Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

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

Lin, X; Sun, T; Yin, Y

Purpose: To study the dosimetric impact of intensity-modulated radiotherapy (IMRT), hybrid intensity-modulated radiotherapy (h-IMRT) and volumetric modulated arc therapy(VMAT) for whole-brain radiotherapy (WBRT) with simultaneous integrated boost in patients with multiple brain metastases. Methods: Ten patients with multiple brain metastases were included in this analysis. The prescribed dose was 45 Gy to the whole brain (PTVWBRT) and 55 Gy to individual brain metastases (PTVboost) delivered simultaneously in 25 fractions. Three treatment techniques were designed: the 7 equal spaced fields IMRT plan, hybrid IMRT plan and VMAT with two 358°arcs. In hybrid IMRT plan, two fields(90°and 270°) were planned to themore » whole brain. This was used as a base dose plan. Then 5 fields IMRT plan was optimized based on the two fields plan. The dose distribution in the target, the dose to the organs at risk and total MU in three techniques were compared. Results: For the target dose, conformity and homogeneity in PTV, no statistically differences were observed in the three techniques. For the maximum dose in bilateral lens and the mean dose in bilateral eyes, IMRT and h-IMRT plans showed the highest and lowest value respectively. No statistically significant differences were observed in the dose of optic nerve and brainstem. For the monitor units, IMRT and VMAT plans showed the highest and lowest value respectively. Conclusion: For WBRT with simultaneous integrated boost in patients with multiple brain metastases, hybrid IMRT could reduce the doses to lens and eyes. It is feasible for patients with brain metastases.« less

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

PubMed

Simão, Vinícius Augusto; Berloffa Belardin, Larissa; Araújo Leite, Gabriel Adan; de Almeida Chuffa, Luiz Gustavo; Camargo, Isabel Cristina Cherici

2015-10-01

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

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

Chang, S; Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression andmore » cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide the added clinical benefit of improving treatment therapeutic ratio. Animal Studies were performed within the LCCC Animal Studies Core Facility at the University of North Carolina at Chapel Hill. The LCCC Animal Studies Core is supported in part by an NCI Center Core Support Grant (CA16086) to the UNC Lineberger Comprehensive Cancer Center.« less

Development of a stable and sensitive semiconductor detector by using a mixture of lead(II) iodide and lead monoxide for NDT radiation dose detection

NASA Astrophysics Data System (ADS)

Heo, Y. J.; Kim, K. T.; Han, M. J.; Moon, C. W.; Kim, J. E.; Park, J. K.; Park, S. K.

2018-03-01

Recently, high-energy radiation has been widely used in various industrial fields, including the medical industry, and increasing research efforts have been devoted to the development of radiation detectors to be used with high-energy radiation. In particular, nondestructive industrial applications use high-energy radiation for ships and multilayered objects for accurate inspection. Therefore, it is crucial to verify the accuracy of radiation dose measurements and evaluate the precision and reproducibility of the radiation output dose. Representative detectors currently used for detecting the dose in high-energy regions include Si diodes, diamond diodes, and ionization chambers. However, the process of preparing these detectors is complex in addition to the processes of conducting dosimetric measurements, analysis, and evaluation. Furthermore, the minimum size that can be prepared for a detector is limited. In the present study, the disadvantages of original detectors are compensated by the development of a detector made of a mixture of polycrystalline PbI2 and PbO powder, which are both excellent semiconducting materials suitable for detecting high-energy gamma rays and X-rays. The proposed detector shows characteristics of excellent reproducibility and stable signal detection in response to the changes in energy, and was analyzed for its applicability. Moreover, the detector was prepared through a simple process of particle-in-binder to gain control over the thickness and meet the specific value designated by the user. A mixture mass ratio with the highest reproducibility was determined through reproducibility testing with respect to changes in the photon energy. The proposed detector was evaluated for its detection response characteristics with respect to high-energy photon beam, in terms of dose-rate dependence, sensitivity, and linearity evaluation. In the reproducibility assessment, the detector made with 15 wt% PbO powder showed the best characteristics of 0.59% and 0.25% at 6 and 15 MV, respectively. Based on its selection in the reproducibility assessment, the 15 wt% PbO detector showed no dependence on the dose-rate changes, with R-SD < 1%. Finally, a coefficient of determination of 1 in the linearity assessment demonstrated very good linearity with regards to changes in dose. These results demonstrate the applicability and usefulness of the proposed detector made from a mixture of PbI2 and PbO semiconductors.

MRI-guided brachytherapy in locally advanced cervical cancer: Small bowel [Formula: see text] and [Formula: see text] are not predictive of late morbidity.

PubMed

Petit, Claire; Dumas, Isabelle; Chargari, Cyrus; Martinetti, Florent; Maroun, Pierre; Doyeux, Kaya; Tailleur, Anne; Haie-Meder, Christine; Mazeron, Renaud

2016-01-01

To establish dose-volume effect correlations for late small bowel (SB) toxicities in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate MRI-guided adaptive brachytherapy. Patients treated with curative intent and followed prospectively were included. The SB loops closed to CTV were delineated, but no specific dose constraint was applied. The dosimetric data, converted in 2-Gy equivalent, were confronted with the occurrence of late morbidity assessed using the CTC-AE 3.0. Dose-effect relationships were assessed using mean-dose comparisons, log-rank tests on event-free periods, and probit analyses. A total of 115 patients with a median followup of 35.5 months were included. Highest grade per patient was: Grades 0 for 17, 1 for 75, 2 for 20, and 3 for 3. The mean [Formula: see text] and [Formula: see text] were, respectively, 68.7 ± 13.6 Gy and 85.8 ± 33.1 Gy and did not differ according to event severity (p = 0.47 and p = 0.52), even when comparing Grades 0-1 vs. 2-4 events (68.0 ± 12.4 vs. 71.4 ± 17.7 Gy; p = 0.38 and 83.7 ± 26.4 vs. 94.5 ± 51.9 Gy; p = 0.33). Log-rank tests were performed after splitting the cohort according to four [Formula: see text] levels: >80 Gy, 70-79 Gy, 60-70 Gy, and <60 Gy. No difference was observed for Grades 1-4, Grades 2-4, or Grades 3-4 (p = 0.21-0.52). Probit analyses showed no correlation between the dosimetric parameters and probability of Grades 1-4, 2-4, or 3-4 events (p = 0.19-0.48). No significant dose-volume effect relationships were demonstrated between the [Formula: see text] and [Formula: see text] and the probability of late SB morbidity. These parameters should not limit the pulsed-dose rate brachytherapy optimization process. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

The effects of tirofiban infusion on clinical and angiographic outcomes of patients with STEMI undergoing primary PCI.

PubMed

Kaymaz, Cihangir; Keleş, Nurşen; Özdemir, Nihal; Tanboğa, İbrahim Halil; Demircan, Hacer C; Can, Mehmet M; Koca, Fatih; İzgi, İbrahim Akın; Özkan, Alper; Türkmen, Muhsin; Kırma, Cevat; Esen, Ali M

2015-11-01

The present study was designed to determine the effects of tirofiban (Tiro) infusion on angiographic measures, ST-segment resolution, and clinical outcomes in patients with STEMI undergoing PCI. Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI), while the most effective timing of administration is still under investigation. A total of 1242 patients (83.0% males, mean (standard deviation; SD) age: 54.7 (10.9) years) with STEMI who underwent primary PCI were included in this retrospective non-randomized study in four groups, composed of no tirofiban infusion [Tiro (-); n=248], tirofiban infusion before PCI (pre-Tiro; n=720), tirofiban infusion during PCI (peri-Tiro; n=50), and tirofiban infusion after PCI (post-Tiro; n=224). In all Tiro (+) patients, bolus administration of Tiro (10 µg/kg) was followed by infusion (0.15 µg/kg/min) for a mean (SD) duration of 22.4±6.8 hours. The pre-PCI Tiro group was associated with the highest percentage of patients with TIMI 3 flow (99.4%; p<0.001), the lowest corrected TIMI frame count [21(18-23.4); p<0.001], the highest percentage of patients with >75% ST-segment resolution (78.1%; p<0.001), and the lowest rate of in-hospital sudden cardiac death and in-hospital all-cause mortality (3.2%, p<0.05, 3.3%, p=0.01). Major bleeding was reported in 18 (1.8%) patients who received tirofiban. Use of standard-dose bolus tirofiban in addition to aspirin, high-dose clopidogrel, and unfractionated heparin prior to primary PCI significantly improves myocardial reperfusion, ST-segment resolution, in-hospital mortality rate, and in-hospital sudden cardiac death in patients with STEMI with no increased risk of major bleeding.

Comparative performance analysis for computer aided lung nodule detection and segmentation on ultra-low-dose vs. standard-dose CT

NASA Astrophysics Data System (ADS)

Wiemker, Rafael; Rogalla, Patrik; Opfer, Roland; Ekin, Ahmet; Romano, Valentina; Bülow, Thomas

2006-03-01

The performance of computer aided lung nodule detection (CAD) and computer aided nodule volumetry is compared between standard-dose (70-100 mAs) and ultra-low-dose CT images (5-10 mAs). A direct quantitative performance comparison was possible, since for each patient both an ultra-low-dose and a standard-dose CT scan were acquired within the same examination session. The data sets were recorded with a multi-slice CT scanner at the Charite university hospital Berlin with 1 mm slice thickness. Our computer aided nodule detection and segmentation algorithms were deployed on both ultra-low-dose and standard-dose CT data without any dose-specific fine-tuning or preprocessing. As a reference standard 292 nodules from 20 patients were visually identified, each nodule both in ultra-low-dose and standard-dose data sets. The CAD performance was analyzed by virtue of multiple FROC curves for different lower thresholds of the nodule diameter. For nodules with a volume-equivalent diameter equal or larger than 4 mm (149 nodules pairs), we observed a detection rate of 88% at a median false positive rate of 2 per patient in standard-dose images, and 86% detection rate in ultra-low-dose images, also at 2 FPs per patient. Including even smaller nodules equal or larger than 2 mm (272 nodules pairs), we observed a detection rate of 86% in standard-dose images, and 84% detection rate in ultra-low-dose images, both at a rate of 5 FPs per patient. Moreover, we observed a correlation of 94% between the volume-equivalent nodule diameter as automatically measured on ultra-low-dose versus on standard-dose images, indicating that ultra-low-dose CT is also feasible for growth-rate assessment in follow-up examinations. The comparable performance of lung nodule CAD in ultra-low-dose and standard-dose images is of particular interest with respect to lung cancer screening of asymptomatic patients.

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

PubMed

Taylor, W Robert; Naw, Htee Khu; Maitland, Kathryn; Williams, Thomas N; Kapulu, Melissa; D'Alessandro, Umberto; Berkley, James A; Bejon, Philip; Okebe, Joseph; Achan, Jane; Amambua, Alfred Ngwa; Affara, Muna; Nwakanma, Davis; van Geertruyden, Jean-Pierre; Mavoko, Muhindo; Lutumba, Pascal; Matangila, Junior; Brasseur, Philipe; Piola, Patrice; Randremanana, Rindra; Lasry, Estrella; Fanello, Caterina; Onyamboko, Marie; Schramm, Birgit; Yah, Zolia; Jones, Joel; Fairhurst, Rick M; Diakite, Mahamadou; Malenga, Grace; Molyneux, Malcolm; Rwagacondo, Claude; Obonyo, Charles; Gadisa, Endalamaw; Aseffa, Abraham; Loolpapit, Mores; Henry, Marie-Claire; Dorsey, Grant; John, Chandy; Sirima, Sodiomon B; Barnes, Karen I; Kremsner, Peter; Day, Nicholas P; White, Nicholas J; Mukaka, Mavuto

2018-01-18

In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.

Health and ecological hazards due to natural radioactivity in soil from mining areas of Nasarawa State, Nigeria.

PubMed

Aliyu, Abubakar Sadiq; Ibrahim, Umar; Akpa, Chidozie Timothy; Garba, Nuraddeen Nasiru; Ramli, Ahmad Termizi

2015-01-01

Nasarawa State is located in north central Nigeria and it is known as Nigeria's home of solid minerals. It is endowed with barite, copper, zinc, tantalite and granite. Continuous releases of mining waste and tailings into the biosphere may result in a build-up of radionuclides in air, water and soil. This work therefore aims to measure the activity concentration levels of primordial radionuclides in the soil/sediment samples collected from selected mines of the mining areas of Nasarawa State. The paper also assesses the radiological and radio ecological impacts of mining activities on the residents of mining areas and their environment. The activity concentrations of primordial radionuclides ((226)Ra, (232)Th and (40)K) in the surface soils/sediment samples were determined using sodium iodide-thallium gamma spectroscopy. Seven major mines were considered with 21 samples taken from each of the mines for radiochemistry analysis. The human health hazard assessment was conducted using regulatory methodologies set by the United Nations Scientific Committee on the Effects of Atomic Radiation, while the radio ecological impact assessment was conducted using the ERICA tool v. 1.2. The result shows that the activity concentrations of (40)K in the water ways of the Akiri copper and the Azara barite mines are 60 and 67% higher than the world average value for (40)K, respectively. In all mines, the annual effective dose rates (mSv y(-1)) were less than unity, and a maximum annual gonadal dose of 0.58 mSv y(-1) is received at the Akiri copper mine, which is almost twice the world average value for gonadal dose. The external hazard indices for all the mines were less than unity. Our results also show that mollusc-gastropod, insect larvae, mollusc-bivalve and zooplankton are the freshwater biotas with the highest dose rates ranging from 5 to 7 µGy h(-1). These higher dose rates could be associated with zinc and copper mining at Abuni and Akiri, respectively. The most exposed terrestrial reference organisms are lichen and bryophytes. In all cases, the radio ecological risks are not likely to be discernible. This paper presents a pioneer data for ecological risk from ionizing contaminants due to mining activity in Nasarawa State, Nigeria. Its methodology could be adopted for future work on radioecology of mining.

Final Technical Report- Radiation Hard Tight Pitch GaInP SPAD Arrays for High Energy Physics

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

Harmon, Eric S.

The specialized photodetectors used in high energy physics experiments often need to remain extremely sensitive for years despite radiation induced damage caused by the constant bombardment of high energy particles. To solve this problem, LightSpin Technologies, Inc. in collaboration with Prof. Bradley Cox and the University of Virginia is developing radiation-hard GaInP photodetectors which are projected to be extraordinarily radiation hard, theoretically capable of withstanding a 100,000-fold higher radiation dose than silicon. In this Phase I SBIR project, LightSpin investigated the performance and radiation hardness of fifth generation GaInP SPAD arrays. These fifth generation devices used a new planar processingmore » approach that enables very tight pitch arrays to be produced. High performance devices with SPAD pitches of 11, 15, and 25 μm were successfully demonstrated, which greatly increased the dynamic range and maximum count rate of the devices. High maximum count rates are critical when considering radiation hardness, since radiation damage causes a proportional increase in the dark count rate, causing SPAD arrays with low maximum count rates (large SPAD pitches) to fail. These GaInP SPAD array Photomultiplier Chips™ were irradiated with protons, electrons, and neutrons. Initial irradiation results were disappointing, with the post-irradiation devices exhibiting excessively high dark currents. The degradation was traced to surface leakage currents that were largely eliminated through the use of trenches etched around the exterior of the Photomultiplier Chip™ (not between SPAD elements). A second round of irradiations on Photomultiplier Chips™ with trenches proved substantially more successful, with post-irradiation dark currents remaining relatively low, though dark count rates were observed to increase at the highest doses. Preliminary analysis of the post-irradiation devices is promising … many of the irradiated Photomultiplier Chips™ still exhibit good gain characteristics after 1E12/cm 2 – 1E13/cm 2 doses and have apparent dark count rates that are lower than the apparent dark count rates published for irradiation of silicon SPAD arrays (silicon photomultipliers or SiPMs). Some post-irradiation results are still pending because the samples will still too radioactive to be shipped back from the irradiation facility for post-irradiation testing.« less

Thermal antinociception after dexmedetomidine administration in cats: a dose-finding study.

PubMed

Slingsby, L S; Taylor, P M

2008-04-01

The optimum dose of dexmedetomidine for antinociception to a thermal stimulus was determined in a crossover study of 12 cats. In five treatment groups (n = 10 per group), dexmedetomidine was administered intramuscularly (i.m.) at 2, 5, 10, 20 and 40 microg/kg; positive and negative controls were administered buprenorphine (20 microg/kg, i.m.) and 0.9% saline (0.006 mL/kg, i.m.) respectively. Baseline thermal thresholds and visual analogue scale (VAS) sedation scores were obtained prior to drug treatment and then at regular intervals until 24 h after administration. The summary measures of overall mean thresholds and overall mean VAS scores were investigated using a univariate general linear model for multiple factors with post hoc Tukey's tests (P < 0.05). Only dexmedetomidine at 40 microg/kg displayed an analgesic effect (less than that of buprenorphine). The VAS for sedation did not significantly affect the thresholds obtained and treatment was the only significant factor to influence VAS. Dexmedetomidine resulted in higher VAS for sedation than saline and buprenorphine. Dexmedetomidine at 40 microg/kg significantly increased nociceptive thresholds compared with saline control, but less than buprenorphine. Dexmedetomidine produced dose-dependent sedation, but only the highest dose produced analgesia, suggesting that induction of analgesia requires the highest dose (or an additional analgesic) in the clinical setting.

SU-E-T-208: Incidence Cancer Risk From the Radiation Treatment for Acoustic Neuroma Patient

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

Kim, D; Chung, W; Shin, D

2014-06-01

Purpose: The present study aimed to compare the incidence risk of a secondary cancer from therapeutic doses in patients receiving intensitymodulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS). Methods: Four acoustic neuroma patients were treated with IMRT, VMAT, or SRS. Their incidnece excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) were estimated using the corresponding therapeutic doses measured at various organs by radio-photoluminescence glass dosimeters (RPLGD) placed inside a humanoid phantom. Results: When a prescription dose was delivered in the planning target volume of the 4 patients, the average organ equivalentmore » doses (OED) at the thyroid, lung, normal liver, colon, bladder, prostate (or ovary), and rectum were measured. The OED decreased as the distance from the primary beam increased. The thyroid received the highest OED compared to other organs. A LAR were estimated that more than 0.03% of AN patients would get radiation-induced cancer. Conclusion: The tyroid was highest radiation-induced cancer risk after radiation treatment for AN. We found that LAR can be increased by the transmitted dose from the primary beam. No modality-specific difference in radiation-induced cancer risk was observed in our study.« less

40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

Code of Federal Regulations, 2011 CFR

2011-07-01

... the control and the top dose group for observation of reversibility, persistence or delayed occurrence... toxicity. (2) Dosage. (i) Generally, at least three test groups and a control group should be used. If... administering the test substance, the control group should receive the vehicle in the highest volume used. (ii...