Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

NASA Technical Reports Server (NTRS)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

PubMed

Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

2015-10-13

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

SU-F-T-301: Planar Dose Pass Rate Inflation Due to the MapCHECK Measurement Uncertainty Function

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

Bailey, D; Spaans, J; Kumaraswamy, L

Purpose: To quantify the effect of the Measurement Uncertainty function on planar dosimetry pass rates, as analyzed with Sun Nuclear Corporation analytic software (“MapCHECK” or “SNC Patient”). This optional function is toggled on by default upon software installation, and automatically increases the user-defined dose percent difference (%Diff) tolerance for each planar dose comparison. Methods: Dose planes from 109 IMRT fields and 40 VMAT arcs were measured with the MapCHECK 2 diode array, and compared to calculated planes from a commercial treatment planning system. Pass rates were calculated within the SNC analytic software using varying calculation parameters, including Measurement Uncertainty onmore » and off. By varying the %Diff criterion for each dose comparison performed with Measurement Uncertainty turned off, an effective %Diff criterion was defined for each field/arc corresponding to the pass rate achieved with MapCHECK Uncertainty turned on. Results: For 3%/3mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.8–1.1% average, depending on plan type and calculation technique, for an average pass rate increase of 1.0–3.5% (maximum +8.7%). For 2%, 2 mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.7–1.2% average, for an average pass rate increase of 3.5–8.1% (maximum +14.2%). The largest increases in pass rate are generally seen with poorly-matched planar dose comparisons; the MapCHECK Uncertainty effect is markedly smaller as pass rates approach 100%. Conclusion: The Measurement Uncertainty function may substantially inflate planar dose comparison pass rates for typical IMRT and VMAT planes. The types of uncertainties incorporated into the function (and their associated quantitative estimates) as described in the software user’s manual may not accurately estimate realistic measurement uncertainty for the user’s measurement conditions. Pass rates listed in published reports or otherwise compared to the results of other users or vendors should clearly indicate whether the Measurement Uncertainty function is used.« less

[Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].

PubMed

Haas, Jigal; Zilberberg, Eran; Kedem, Alon; Dar, Shir; Orvieto, Raoul

2015-02-01

We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome. All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose. Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate. In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

Outcome of stroke patients receiving different doses of recombinant tissue plasminogen activator.

PubMed

Ong, Cheung-Ter; Wong, Yi-Sin; Wu, Chi-Shun; Su, Yu-Hsiang

2017-01-01

Intravenous recombinant tissue plasminogen activator (tPA) at a dose of 0.9 mg/kg body weight is associated with a high hemorrhagic transformation (HT) rate. Low-dose tPA (0.6 mg/kg) may have a lower hemorrhage rate but the mortality and disability rates at 90 days cannot be confirmed as non-inferior to standard-dose tPA. Whether the doses 0.7 and 0.8 mg/kg have better efficacy and safety needs further investigation. Therefore, this study is to compare the efficacy and safety of each dose of tPA (0.6, 0.7, 0.8, and 0.9 mg/kg body weight) and to investigate the factors affecting early neurological improvement (ENI) and early neurological deterioration (END). For this observational study, data were obtained from 274 patients who received tPA thrombolytic therapy in Chia-Yi Christian Hospital stroke unit. The tPA dose was given at the discretion of each physician. The definition of ENI was a >8 point improvement (compared with baseline) at 24 h following thrombolytic therapy or an improvement in the National Institutes of Health Stroke Score (NIHSS) to 0 or 1 toward the end of tPA infusion. The definition of END was a >4 point increase in NIHSS (compared with baseline) within 24 h of tPA infusion. The primary objective was to investigate whether 0.7 and 0.8 mg/kg of tPA have higher ENI rate, lower END rate, and better outcome at 6 months. Poor outcome was defined as having a modified Rankin Scale of 3 to 6 (range, 0 [no symptoms] to 6 [death]). The secondary objective was to investigate whether low-dose tPA has a lower risk of intracerebral HT than that with standard-dose tPA. We also investigated the factors affecting ENI, END, HT, and 6-month outcome. A total of 274 patients were included during the study period, of whom 260 were followed up for >6 months. There was a trend for the HT rate to increase as the dose increased ( P =0.02). The symptomatic HT rate was not significantly different among the low-dose and standard-dose groups. The ENI and END ( P =0.52) were not significantly different among the four dosage groups. The clinical functional outcome at 6 months after stroke onset was poorer in the standard-dose group ( P =0.02). Stroke severity ( P <0.01), stroke type ( P =0.03), and diabetes mellitus ( P =0.04) affected the functional outcome at 6 months. Among the 274 patients receiving tPA thrombolytic therapy, the HT rate increased as dose increased. The symptomatic HT, ENI and END rates were not significantly different among the low-dose (0.6, 0.7, and 0.8 mg/kg) and standard-dose groups. Stroke severity (NIHSS >12), stroke type (cardioembolism and large artery atherosclerosis) and diabetes mellitus were associated with poor outcome at 6 months.

Effects of gamma irradiation dose-rate on sterile male Aedesaegypti

NASA Astrophysics Data System (ADS)

Ernawan, Beni; Tambunan, Usman Sumo Friend; Sugoro, Irawan; Sasmita, Hadian Iman

2017-06-01

Aedesaegypti is the most important vector for dengue, yellow fever and Zika viruses. Considering its medical importance, vector population control program utilizing radiation-based sterile insect technique (SIT) is one of the potential methods for preventing and limiting the dispersal of these viruses. The present study was undertaken to evaluate the dose-rates effects of γ-sterilization on quality parameters of sterile males. Males Ae.aegypti at the pupal stage were sterilized by applying 70 Gyγ-rays in varies dose-rates, i.e. 0 (control), 300, 600, 900, 1200 and 1500Gy/h utilizing panoramic irradiator. Adult males that emerged from the pupal stage were assessed for their quality parameters, which are the percentage of emergence, longevity, sterility and mating competitiveness. The results herein indicate that there was no major effect of dose-rate on the percentage of emergence, the data showedthat there were no differences between irradiated males compared with control. Generally, the longevity of irradiated males was lower compared to control. The data also demonstrated that longevity was significantly increased at the dose-rate from 300 to 900Gy/h, then decreased at the dose-rate 900 to 1500 Gy/h. Sterility of irradiated maleswas significantly different compared to control, while there was no significantly different at dose rate 300 to 1500 Gy/h. Mating competitiveness of irradiated males was increased at the dose rate from 300 to 1200 Gy/h, then the value was decreased significantly at the dose rate 1500 Gy/h. The dose-rate effects of γ-sterilization were discussed in the context genetic vector control, in particular, the SIT. The results give information and contribute to better understanding towards γ-sterilization optimization and quality parameters of sterile male Ae. aegypti on SIT methods.

High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

PubMed Central

Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

2013-01-01

Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

Benzodiazepine sensitivity in normal human subjects.

PubMed

Hommer, D W; Matsuo, V; Wolkowitz, O; Chrousos, G; Greenblatt, D J; Weingartner, H; Paul, S M

1986-06-01

Increasing intravenous doses of diazepam or placebo were administered to ten healthy normal volunteers, and the changes in saccadic eye velocity, self-rated sedation and anxiety, and plasma cortisol and growth hormone concentrations were measured. Diazepam administration (4.4 to 140 micrograms/kg, cumulative dose) resulted in a dose-dependent decrease in saccadic eye velocity and plasma cortisol level as well as a dose-dependent increase in self-rated sedation and plasma growth hormone level. Self-rated anxiety was unaffected in these relatively nonanxious subjects. The diazepam-induced changes in saccadic eye velocity, sedation, and growth hormone and cortisol levels were highly correlated with each other and with increasing plasma diazepam concentration. These results are consistent with a benzodiazepine receptor-mediated action of diazepam. The highly quantifiable and dose-dependent decrease in saccadic eye velocity by benzodiazepines should make this a useful measure of benzodiazepine receptor sensitivity in humans.

Effect of the dose of exogenous fibrolytic enzyme preparations on preingestive fiber hydrolysis, ruminal fermentation, and in vitro digestibility of bermudagrass haylage.

PubMed

Romero, J J; Zarate, M A; Adesogan, A T

2015-01-01

Our objectives were to evaluate the effects of the dose rates of 5 Trichoderma reesei and Aspergillus oryzae exogenous fibrolytic enzymes (EFE; 1A, 2A, 11C, 13D, and 15D) on in vitro digestibility, fermentation characteristics, and preingestive hydrolysis of bermudagrass haylage and to identify the optimal dose of each EFE for subsequent in vitro and in vivo studies. In experiment 1, EFE were diluted in citrate-phosphate buffer (pH 6) and applied in quadruplicate in each of 2 runs at 0× (control), 0.5×, 1×, 2×, and 3×; where 1× was the respective manufacturer-recommended dose (2.25, 2.25, 10, 15, and 15g of EFE/kg of dry matter). The suspension was incubated for 24h at 25°C and for a further 24h at 39°C after the addition of ruminal fluid. In experiment 2, a similar approach to that in experiment 1 was used to evaluate simulated preingestive effects, except that sodium azide (0.02% wt/vol) was added to the EFE solution. The suspension was incubated for 24h at 25°C and then 15mL of water was added before filtration to extract water-soluble compounds. For both experiments, data for each enzyme were analyzed separately as a completely randomized block design with a model that included effects of EFE dose, run, and their interaction. In experiment 1, increasing the EFE dose rate nonlinearly increased the DM digestibility of 1A, 2A, 11C, and 13D and the neutral detergent fiber digestibility (NDFD) of 1A, 2A, 11C, and 13D. Optimal doses of 1A, 2A, 11C, 13D, and 15D, as indicated by the greatest increases in NDFD at the lowest dose tested, were 2×, 2×, 1×, 0.5×, and 0.5×, respectively. Increasing the dose rate of 2A, 11C, and 13D nonlinearly increased concentrations of total volatile fatty acids and propionate (mM), decreased their acetate-to-propionate ratios and linearly decreased those of samples treated with 1A and 15D. In experiment 2, increasing the dose rate of each EFE nonlinearly decreased concentrations of netural detergent fiber; also, increasing the dose rate of 1A, 2A, 11C, and 1D nonlinearly increased concentrations of water-soluble carbohydrates and free ferulic acid (μg/g). Application of increasing doses of the EFE increased NDF hydrolysis, NDFD, and ruminal fluid fermentation of bermudagrass haylage, but the optimal dose varied with the EFE. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

NASA Technical Reports Server (NTRS)

Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT cells and misrejoined breaks increased in both cell lines. The present study suggests that AT cells begin to rejoin breaks when a certain number of breaks are accumulated and an increased number of exchanges were observed in G0 AT cells, which is similar situation after high-dose-rate irradiation.

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.

Immediate effects of 33 to 180 rad/min (60)Co exposure on performance and blood pressure in monkeys. Topical report

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

Bruner, A.

1976-09-01

Four groups of monkeys received 1000 rads (60)Co at 33, 50, 75, or 180 rad/min wholebody irradiation while performing a delayed matching-to-sample task. Systematic dose rate effects were observed on performance and blood pressure within the initial 20 min postirradiation. The incidence and severity of performance decrement (PD) increased with higher dose rate. The appearance of postirradiation hypotension was systematically delayed and its rate of fall prolonged as dose rate was lower. The hypotension likewise appeared less deep with lower dose rate exposure. Based on the calculated cumulative dose absorbed at the time of symptom appearance two coactive thresholds weremore » proposed to exist: a total dose threshold of approximately 300 rads (midbody measurement), and a dose rate threshold of about 25 rad/min.« less

Dose-response characteristics of an amorphous silicon EPID.

PubMed

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output characteristics of the accelerator. If ghosting is prevented from affecting the results and all dose-response effects are properly corrected for, the EPID signal becomes independent of dose rate, dose, and exposure time.

SU-G-JeP2-09: Minimal Skin Dose Increase in Longitudinal Rotating Biplanar Linac-MR Systems: Examination of Radiation Energy and Flattening Filter Design

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

Fallone, B; Keyvanloo, A; Burke, B

Purpose: To quantify increase in entrance skin-dose due to magnetic fields of the Alberta longitudinal linac-MR by examining the effect of radiation energy and flattening filter, using Monte Carlo calculations and accurate 3-D models of the magnetic field. Methods: The 3-D magnetic fields generated by the bi-planar Linac-MR are calculated with FEM using Opera-3D. BEAMnrc simulates the particle phase-space in the presence of the rapidly decaying fringe field of 0.5T MRI assembled with a Varian 600C linac with an isocentre distance of 130 cm for 6 MV and 10 MV beams. Skin doses are calculated at an average depth ofmore » 70 µm using DOSXYZnrc with varying SSDs and field sizes. Furthermore, flattening filters are reshaped to compensate for the significant drop in dose rate due to increased SAD of 130 cm and skin-doses are evaluated. Results: The confinement effect of the MRI fringe field on the contaminant electrons is minimal. For SSDs of 100 – 120 cm the increase in skin dose is ∼6% – 19% and ∼1% – 9% for the 6 and 10 MV beams, respectively. For 6MV, skin dose increases from ∼10.5% to 1.5%. for field-size increases of 5×5 cm2 to 20×20 cm2. For 10 MV, skin dose increases by ∼6% for a 5×5 cm2 field, and decreases by ∼1.5% for a 20×20 cm2 field. The reshaped flattening filter increases the dose rate from 355 MU/min to 529 MU/min (6 MV) or 604 MU/min (10 MV), while the skin-dose increases by only an additional ∼2.6% (all percent increases in skin dose are relative to Dmax). Conclusion: There is minimal increase in the entrance skin dose and minimal/no decrease in the dose rate of the Alberta longitudinal linac-MR system. There is even lower skin-dose increase at 10 MV. Funding: Alberta Innovates - Health Solutions (AIHS) Conflict of Interest: Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization)« less

Remediation of incomplete nitrification and capacity increase of biofilters at different drinking water treatment plants through copper dosing.

PubMed

Wagner, Florian B; Nielsen, Peter Borch; Boe-Hansen, Rasmus; Albrechtsen, Hans-Jørgen

2018-04-01

Drinking water treatment plants based on groundwater may suffer from incomplete ammonium removal, which deteriorates drinking water quality and constrains water utilities in the operation of their plants. Ammonium is normally removed through nitrification in biological granular media filters, and recent studies have demonstrated that dosing of copper can stimulate the removal of ammonium. Here, we investigated if copper dosing could generically improve ammonium removal of biofilters, at treatment plants with different characteristics. Copper was dosed at ≤1.5 μg Cu/L to biofilters at 10 groundwater treatment plants, all of which had displayed several years of incomplete nitrification. Plants exceeded the Danish national water quality standard of 0.05 mg NH 4 + /L by a factor of 2-12. Within only 2-3 weeks of dosing, ammonium removal rates increased significantly (up to 150%). Nitrification was fully established, with ammonium effluent concentrations of <0.01 mg NH 4 + -N/L at most plants, regardless of the differences in raw water chemistry, ammonium loading rates, filter design and operation, or treatment plant configuration. However, for filters without primary filtration, it took longer time to reach complete ammonium removal than for filters receiving prefiltered water, likely due to sorption of copper to iron oxides, at plants without prefiltration. With complete ammonium removal, we subjected two plants to short-term loading rate upshifts, to examine the filters' ability to cope with loading rate variations. After 2 months of dosing and an average loading rate of 1.0 g NH 4 + -N/m 3 filter material/h, the loading rate was upshifted by 50%. Yet, a filter managed to completely remove all the influent ammonium, showing that with copper dosing the filter had extra capacity to remove ammonium even beyond its normal loading rates. Depth sampling revealed that the ammonium removal rate of the filter's upper 10 cm increased more than 7-fold from 0.67 to 4.90 g NH 4 + -N/m 3 /h, and that nitrite produced from increased ammonium oxidation was completely oxidized further to nitrate. Hence, no problems with nitrite accumulation or breakthrough occurred. Overall, copper dosing generically enhanced nitrification efficiency and allowed a range of quite different plants to meet water quality standards, even at increased loading rates. The capacity increase is highly relevant in practice, as it makes filters more robust towards sudden ammonium loading rate variations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dose rate effects in radiation degradation of polymer-based cable materials

NASA Astrophysics Data System (ADS)

Plaček, V.; Bartoníček, B.; Hnát, V.; Otáhal, B.

2003-08-01

Cable ageing under the nuclear power plant (NPP) conditions must be effectively managed to ensure that the required plant safety and reliability are maintained throughout the plant service life. Ionizing radiation is one of the main stressors causing age-related degradation of polymer-based cable materials in air. For a given absorbed dose, radiation-induced damage to a polymer in air environment usually depends on the dose rate of the exposure. In this work, the effect of dose rate on the degradation rate has been studied. Three types of NPP cables (with jacket/insulation combinations PVC/PVC, PVC/PE, XPE/XPE) were irradiated at room temperature using 60Co gamma ray source at average dose rates of 7, 30 and 100 Gy/h with the doses up to 590 kGy. The irradiated samples have been tested for their mechanical properties, thermo-oxidative stability (using differential scanning calorimetry, DSC), and density. In the case of PVC and PE samples, the tested properties have shown evident dose rate effects, while the XPE material has shown no noticeable ones. The values of elongation at break and the thermo-oxidative stability decrease with the advanced degradation, density tends to increase with the absorbed dose. For XPE samples this effect can be partially explained by the increase of crystallinity. It was tested by the DSC determination of the crystalline phase amount.

Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris

DOE PAGES

Stark, Karolina; Scott, David E.; Tsyusko, Olga; ...

2015-04-30

Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad ( Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments didmore » not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less

Spacecraft shielding for a Mars mission

NASA Astrophysics Data System (ADS)

O'Brien, K.

Calculations of the effective radiation dose due to cosmic rays in the interplanetary medium between Earth and Mars show that, as in the atmosphere above the Pfotzer Maximum, the dose rate increases with increasing wall thickness. An unshielded space crew member would receive almost 70 rem (0.70 Sv) a year. The effect of a typically proposed composite space-craft hull of aluminum and polyethylene would increase the dose rate by a few percent. However, 100 g/cm2 of almost any light material would more than double the cosmic radiation exposure of the crew.

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

PubMed

Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

PubMed Central

Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p < 0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p = 0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p = 0.036) but not at 5 (p > 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

PubMed Central

Vaiserman, Alexander M.

2010-01-01

Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

High dose-per-pulse electron beam dosimetry - A model to correct for the ion recombination in the Advanced Markus ionization chamber.

PubMed

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

2017-03-01

The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose-per-pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two-voltage-analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source-to-surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose-response, in beams with varying dose rate/dose-per-pulse, with the chamber together with dose rate/dose-per-pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose-per-pulse (10 -2  ≤ mean dose rate ≤ 10 3 Gy/s, 10 2  ≤ mean dose rate within pulse ≤ 10 7  Gy/s, 10 -4  ≤ dose-per-pulse ≤ 10 1  Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. The results demonstrate how the ion collection efficiency of the chamber decreased as the dose-per-pulse increased, and that the ion recombination was dependent on the dose-per-pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose-per-pulse range, but only for a low polarizing chamber voltage (50 V). However, the two-voltage-analysis method and the Burns & McEwen equation only agreed with the data at low dose-per-pulse values (≤ 10 -2 and ≤ 10 -1  Gy, respectively). An empirical model of the ion recombination in the chamber was found by fitting a logistic function to the data. The ion collection efficiency of the Advanced Markus ionization chamber decreases for measurements in electron beams with increasingly higher dose-per-pulse. However, this chamber is still functional for dose measurements in beams with dose-per-pulse values up toward and above 10 Gy, if the ion recombination is taken into account. Our results show that existing models give a less-than-accurate description of the observed ion recombination. This motivates the use of the presented empirical model for measurements with the Advanced Markus chamber in high dose-per-pulse electron beams, as it enables accurate absorbed dose measurements (uncertainty estimation: 2.8-4.0%, k = 1). The model depends on the dose-per-pulse in the beam, and it is also influenced by the polarizing chamber voltage, with increasing ion recombination with a lowering of the voltage. © 2017 American Association of Physicists in Medicine.

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates.

PubMed

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-02-08

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field.

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates

PubMed Central

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-01-01

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field. PMID:29419782

Radiation exposure in the remote period after the Chernobyl accident caused oxidative stress and genetic effects in Scots pine populations

NASA Astrophysics Data System (ADS)

Volkova, Polina Yu.; Geras'Kin, Stanislav A.; Kazakova, Elizaveta A.

2017-02-01

Even 30 years after the Chernobyl accident, biological effects of irradiation are observed in the chronically exposed Scots pine populations. Chronic radiation exposure at dose rates above 50 mGy•yr-1 caused oxidative stress and led to the increase of antioxidants concentrations in these populations. Genetic variability was examined for 6 enzymes and 14 enzymatic loci of 6 Scots pine populations. Dose rates over 10 mGy•yr-1 caused the increased frequency of mutations and changes in genetic structure of Scots pine populations. However, the same dose rates had no effect on enzymatic activities. The results indicate that even relatively low dose rates of radiation can be considered as an ecological factor which should be taken into account for ecological management and radiation protection of biota species.

Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

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

Perez, Bradford A.; Mettu, Pradeep; Vajzovic, Lejla

2014-05-01

Purpose: To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex. Methods and Materials: A retrospective review was performed to evaluate patients treated for uveal melanoma with {sup 125}I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpointmore » variables. Results: One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001). Conclusions: Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis–free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.« less

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.

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

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.

PubMed

Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H; Hull, Robert; Davis, Mary; Yu, Han-Gang

2015-11-15

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 μg/kg) decreased resting heart rate; at high doses (150-300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. Copyright © 2015 the American Physiological Society.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor

PubMed Central

Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H.; Hull, Robert; Davis, Mary

2015-01-01

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1–30 μg/kg) decreased resting heart rate; at high doses (150–300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03–0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. PMID:26408544

Effects of Methylphenidate on Sleep Functioning in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Becker, Stephen P; Froehlich, Tanya E; Epstein, Jeffery N

2016-06-01

To examine the effects of stimulant medication on the sleep functioning of children with attention-deficit/hyperactivity disorder (ADHD) and identify predictors of sleep problems as a side effect of taking stimulant medication. One hundred sixty-three stimulant-naïve children (72% boys) aged 7 to 11 years diagnosed with ADHD (120 with ADHD predominantly inattentive type, 43 with ADHD combined type) participated in a 4-week, randomized, double-blind, placebo-controlled trial of once-daily (long-acting) methylphenidate (MPH). Parents completed weekly side-effect ratings including an item related to sleep problems. Ten percent of patients had parent-rated sleep problems before the initiation of medication. Rates of parent-rated sleep problems during MPH titration generally increased with increasing MPH dose (placebo: 8%; low dose: 18%; medium dose: 15%; high dose: 25%). Differences emerged between children with (n = 16) or without (n = 147) preexisting sleep problems. Although 23% of children without preexisting sleep problems went on to have sleep problems at the highest MPH dose, only 37.5% of children with preexisting sleep problems still had sleep problems at the highest MPH dose. Lower weight and lower body mass index (BMI) were associated with increased sleep problems during MPH titration. This study demonstrated a general association between increased MPH dose and increased sleep problems in children with ADHD, particularly for children of lower weight/BMI. However, a substantial proportion of children with preexisting sleep difficulties no longer had sleep problems on the highest MPH dose, which may help explain mixed findings reported to date in studies examining the impact of MPH on sleep functioning in children with ADHD and suggests that MPH dose titration should not be avoided solely on the basis of a child's premorbid sleep problems. Future research is needed to replicate and extend these findings to more specific domains of sleep functioning and to identify differences between children with persistent or improved sleep functioning as a result of MPH use.

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

PubMed

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

PubMed Central

Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y.; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong

2011-01-01

This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

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.

The role of temperature increase rate in combinational hyperthermia chemotherapy treatment

NASA Astrophysics Data System (ADS)

Tang, Yuan; McGoron, Anthony J.

2010-02-01

Hyperthermia in combination with chemotherapy has been widely used in cancer treatment. Our previous study has shown that rapid rate hyperthermia in combination with chemotherapy can synergistically kill cancer cells whereas a sub-additive effect was found when a slow rate hyperthermia was applied. In this study, we explored the basis of this difference. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. P-glycoprotein (P-gp) expression, Caspase 3 activity, and heat shock protein 70 (HSP 70) expression following the two different modes of heating were measured. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. Slow rate hyperthermia was provided by a cell culture incubator. Two sets of thermal doses were delivered by either slow rate or rapid rate hyperthermia. HSP70 expression was highly elevated under low dose slow rate incubator hyperthermia while maintained at the baseline level under the other three treatments. Caspase3 level slightly increased after low dose slow rate incubator hyperthermia while necrotic cell death was found in the other three types of heat treatment. In conclusion, when given at the same thermal dose, slow rate hyperthermia is more likely to induce thermotolerance. Meanwhile, hyperthermia showed a dose dependent capability in reversing P-gp mediated MDR; when MDR is reversed, the combinational treatment induced extensive necrotic cell death. During this process, the rate of heating also played a very important role; necrosis was more dramatic in rapid rate hyperthermia than in slow rate hyperthermia even though they were given at the same dose.

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

Effect of Ion Flux (Dose Rate) in Source-Drain Extension Ion Implantation for 10-nm Node FinFET and Beyond on 300/450mm Platforms

NASA Astrophysics Data System (ADS)

Shen, Ming-Yi

The improvement of wafer equipment productivity has been a continuous effort of the semiconductor industry. Higher productivity implies lower product price, which economically drives more demand from the market. This is desired by the semiconductor manufacturing industry. By raising the ion beam current of the ion implanter for 300/450mm platforms, it is possible to increase the throughput of the ion implanter. The resulting dose rate can be comparable to the performance of conventional ion implanters or higher, depending on beam current and beam size. Thus, effects caused by higher dose rate must be investigated further. One of the major applications of ion implantation (I/I) is source-drain extension (SDE) I/I for the silicon FinFET device. This study investigated the dose rate effects on the material properties and device performance of the 10-nm node silicon FinFET. In order to gain better understanding of the dose rate effects, the dose rate study is based on Synopsys Technology CAD (TCAD) process and device simulations that are calibrated and validated using available structural silicon fin samples. We have successfully shown that the kinetic monte carlo (KMC) I/I simulation can precisely model both the silicon amorphization and the arsenic distribution in the fin by comparing the KMC simulation results with TEM images. The results of the KMC I/I simulation show that at high dose rate more activated arsenic dopants were in the source-drain extension (SDE) region. This finding matches with the increased silicon amorphization caused by the high dose-rate I/I, given that the arsenic atoms could be more easily activated by the solid phase epitaxial regrowth process. This increased silicon amorphization led to not only higher arsenic activation near the spacer edge, but also less arsenic atoms straggling into the channel. Hence, it is possible to improve the throughput of the ion implanter when the dopants are implanted at high dose rate if the same doping level with a lower wafer dose can be achieved. In addition, the leakage current might also be reduced due to less undesired dopants in the channel. However, the twin defects from the problematic Si{111} recrystallization is well-known to cause excessive leakage current to the FinFET. This drawback can offset the benefits of the high dose rate I/I mentioned above. This work produced the first attempt at simulating the electrical impact of twin defects on advanced-node (10 nm) FinFET device performance. It was found that the high dose-rate I/I causes more twin defects in the silicon fin, and the physical locations of these defects were close to the channel. The defects undesirably induced trap-assisted band-to-band tunneling near the drain, which increased the leakage current. This issue could be mitigated by using asymmetrical gate overlap/underlap design or thicker spacer for SDE I/I so that the twin defects are not located in the depletion region near the drain.

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.

Summary of LET spectra and dose measurements on ten STS missions

NASA Technical Reports Server (NTRS)

1995-01-01

A comparison of linear energy transfer (LET) spectra measurements made with plastic nuclear track detectors (PNTD's) from area passive dosimeters (APD's), was made for ten different STS missions under similar shielding. The results show that integral flux, dose rate and equivalent dose rate values follow a general increase with respect to increasing orbital inclination and altitude but that there are large variations from a simple relationship. This is to be expected since it has been shown that Shuttle attitude variations, combined with the anisotropic particle flux at the South Atlantic Anomaly (SAA), can result in differences of a factor of 2 in dose rate inside the Shuttle (Badhwar et al., 1995). Solar cycle and shielding differences also result in variations in radiation dose between STS missions. Spaceflight dosimeters from the STS missions are also being used in the development of a method for increasing LET spectra measurement accuracy by extending LET measurements to particle tracks of ranges 10-80 microns. Refinements in processing and measurement techniques for the flight PNTD's have yielded increased detection efficiencies for the short tracks when LET spectra determined by using the standard and refined methods were intercompared.

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

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

THOMAS, PAUL; JANAVE, M. T.

Mangoes were gamma-irradiated at a dose rate of 4 Krad per min in doses of 15 to 200 Krad. Methods are described for extraction of the enzyme, assay of enzyme activity, and estimation of total phenolic constituents, ascorbic acid, and pH. Above doses of 75 Krad discoloration increased with dose and longer storage periods. An increase in activity of polyphenol oxidase was found with increasing radiation doses; a several-fold increase was observed at 200 Krad. This increase was correlated with external manifestations of radiation injury. Possible ways in which the activation of polyphenol oxidase in mango fruits is brought aboutmore » by irradiation are discussed. (HLW)« less

Three-dimensional dosimetric considerations from different point A definitions in cervical cancer low-dose-rate brachytherapy

PubMed Central

Chen, Ting; Kim, Leonard H.; Nelson, Carl; Gabel, Molly; Narra, Venkat; Haffty, Bruce; Yue, Ning J.

2013-01-01

Purpose To investigate the dosimetric difference due to the different point A definitions in cervical cancer low-dose-rate (LDR) intracavitary brachytherapy. Material and methods Twenty CT-based LDR brachytherapy plans of 11 cervical patients were retrospectively reviewed. Two plans with point As following the modified Manchester system which defines point A being 2 cm superior to the cervical os along the tandem and 2 cm lateral (Aos), and the American Brachytherapy Society (ABS) guideline definition in which the point A is 2 cm superior to the vaginal fornices instead of os (Aovoid) were generated. Using the same source strength, two plans prescribed the same dose to Aos and Aovoid. Dosimetric differences between plans including point A dose rate, treatment volume encompassed by the prescription isodose line (TV), and dose rate of 2 cc of the rectum and bladder to the prescription dose were measured. Results On average Aovoid was 8.9 mm superior to Aos along the tandem direction with a standard deviation of 5.4 mm. With the same source strength and arrangement, Aos dose rate was 19% higher than Aovoid dose rate. The average TV(Aovoid) was 118.0 cc, which was 30% more than the average TV(Aos) of 93.0 cc. D2cc/D(Aprescribe) increased from 51% to 60% for rectum, and increased from 89% and 106% for bladder, if the prescription point changed from Aos to Aovoid. Conclusions Different point A definitions lead to significant dose differences. Careful consideration should be given when changing practice from one point A definition to another, to ensure dosimetric and clinical equivalency from the previous clinical experiences. PMID:24474971

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

PubMed

Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

2016-09-01

To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

A cumulative dose comparison between salbutamol and fenoterol metered dose aerosols in asthmatic patients.

PubMed Central

Bellamy, D.; Penketh, A.

1987-01-01

The potency and side effects of salbutamol and fenoterol inhalers have been compared in 8 asthmatic patients using a dose response curve. There was no significant difference in the absolute or percentage increase in FEV1 with the two treatments, but fenoterol caused a significantly greater (P less than 0.01) increase in heart rate than did salbutamol. A greater degree of bronchodilatation was observed with increased doses and we suggest that regular higher doses may provide better bronchodilatation and control of asthma in selected patients. PMID:3432172

The Impact of Dose Rate on the Accuracy of Step-and-Shoot Intensity-modulated Radiation Therapy Quality Assurance Using Varian 2300CD.

PubMed

Njeh, Christopher F; Salmon, Howard W; Schiller, Claire

2017-01-01

Intensity-modulated radiation therapy (IMRT) delivery using "step-and-shoot" technique on Varian C-Series linear accelerator (linac) is influenced by the communication frequency between the multileaf collimator and linac controllers. Hence, the dose delivery accuracy is affected by the dose rate. Our aim was to quantify the impact of using two dose rates on plan quality assurance (QA). Twenty IMRT patients were selected for this study. The plan QA was measured at two different dose rates. A gamma analysis was performed, and the degree of plan modulation on the QA pass rate was also evaluated in terms of average monitor unit per segment (MU/segment) and the total number of segments. The mean percentage gamma pass rate of 94.9% and 93.5% for 300 MU/min and 600 MU/min dose rate, respectively, was observed. There was a significant ( P = 0.001) decrease in percentage gamma pass rate when the dose rate was increased from 300 MU/min to 600 MU/min. There was a weak, but significant association between the percentage pass rate at both dose rate and total number of segments. The total number of MU was significantly correlated to the total number of segments ( r = 0.59). We found a positive correlation between the percentage pass rate and mean MU/segment, r = 0.52 and r = 0.57 for 300 MU/min and 600 MU/min, respectively. IMRT delivery using step-and-shoot technique on Varian 2300CD is impacted by the dose rate and the total amount of segments.

Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

PubMed

Roache, J D; Grabowski, J; Schmitz, J M; Creson, D L; Rhoades, H M

2000-02-01

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.

Methodological variations and their effects on reported medication administration error rates.

PubMed

McLeod, Monsey Chan; Barber, Nick; Franklin, Bryony Dean

2013-04-01

Medication administration errors (MAEs) are a problem, yet methodological variation between studies presents a potential barrier to understanding how best to increase safety. Using the UK as a case-study, we systematically summarised methodological variations in MAE studies, and their effects on reported MAE rates. Nine healthcare databases were searched for quantitative observational MAE studies in UK hospitals. Methodological variations were analysed and meta-analysis of MAE rates performed using studies that used the same definitions. Odds ratios (OR) were calculated to compare MAE rates between intravenous (IV) and non-IV doses, and between paediatric and adult doses. We identified 16 unique studies reporting three MAE definitions, 44 MAE subcategories and four different denominators. Overall adult MAE rates were 5.6% of a total of 21 533 non-IV opportunities for error (OE) (95% CI 4.6% to 6.7%) and 35% of a total of 154 IV OEs (95% CI 2% to 68%). MAEs were five times more likely in IV than non-IV doses (pooled OR 5.1; 95% CI 3.5 to 7.5). Including timing errors of ±30 min increased the MAE rate from 27% to 69% of 320 IV doses in one study. Five studies were unclear as to whether the denominator included dose omissions; omissions accounted for 0%-13% of IV doses and 1.8%-5.1% of non-IV doses. Wide methodological variations exist even within one country, some with significant effects on reported MAE rates. We have made recommendations for future MAE studies; these may be applied both within and outside the UK.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors.

PubMed

Karsch, L; Beyreuther, E; Burris-Mog, T; Kraft, S; Richter, C; Zeil, K; Pawelke, J

2012-05-01

The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

Dose rate dependence for different dosimeters and detectors: TLD, OSL, EBT films, and diamond detectors

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

Karsch, L.; Beyreuther, E.; Burris-Mog, T.

Purpose: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10{sup 11} Gy/s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. Methods: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the numbermore » of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. Results: The dosimeters are dose rate independent up to 410{sup 9} Gy/s within 2% (OSL and TLD) and up to 1510{sup 9} Gy/s within 5% (EBT films). The diamond detectors show strong dose rate dependence. Conclusions: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.« less

Tolerance to effects of high-dose oral δ9-tetrahydrocannabinol and plasma cannabinoid concentrations in male daily cannabis smokers.

PubMed

Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; McMahon, Robert P; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

2013-01-01

Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Δ9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects.

Effect of Intrathecal Bupivacaine Dose on the Success of External Cephalic Version for Breech Presentation: A Prospective, Randomized, Blinded Clinical Trial.

PubMed

Chalifoux, Laurie A; Bauchat, Jeanette R; Higgins, Nicole; Toledo, Paloma; Peralta, Feyce M; Farrer, Jason; Gerber, Susan E; McCarthy, Robert J; Sullivan, John T

2017-10-01

Breech presentation is a leading cause of cesarean delivery. The use of neuraxial anesthesia increases the success rate of external cephalic version procedures for breech presentation and reduces cesarean delivery rates for fetal malpresentation. Meta-analysis suggests that higher-dose neuraxial techniques increase external cephalic version success to a greater extent than lower-dose techniques, but no randomized study has evaluated the dose-response effect. We hypothesized that increasing the intrathecal bupivacaine dose would be associated with increased external cephalic version success. We conducted a randomized, double-blind trial to assess the effect of four intrathecal bupivacaine doses (2.5, 5.0, 7.5, 10.0 mg) combined with fentanyl 15 μg on the success rate of external cephalic version for breech presentation. Secondary outcomes included mode of delivery, indication for cesarean delivery, and length of stay. A total of 240 subjects were enrolled, and 239 received the intervention. External cephalic version was successful in 123 (51.5%) of 239 patients. Compared with bupivacaine 2.5 mg, the odds (99% CI) for a successful version were 1.0 (0.4 to 2.6), 1.0 (0.4 to 2.7), and 0.9 (0.4 to 2.4) for bupivacaine 5.0, 7.5, and 10.0 mg, respectively (P = 0.99). There were no differences in the cesarean delivery rate (P = 0.76) or indication for cesarean delivery (P = 0.82). Time to discharge was increased 60 min (16 to 116 min) with bupivacaine 7.5 mg or higher as compared with 2.5 mg (P = 0.004). A dose of intrathecal bupivacaine greater than 2.5 mg does not lead to an additional increase in external cephalic procedural success or a reduction in cesarean delivery.

Radiation-Induced Carcinogenesis: Mechanistically Based Differences between Gamma-Rays and Neutrons, and Interactions with DMBA

PubMed Central

Shuryak, Igor; Brenner, David J.; Ullrich, Robert L.

2011-01-01

Different types of ionizing radiation produce different dependences of cancer risk on radiation dose/dose rate. Sparsely ionizing radiation (e.g. γ-rays) generally produces linear or upwardly curving dose responses at low doses, and the risk decreases when the dose rate is reduced (direct dose rate effect). Densely ionizing radiation (e.g. neutrons) often produces downwardly curving dose responses, where the risk initially grows with dose, but eventually stabilizes or decreases. When the dose rate is reduced, the risk increases (inverse dose rate effect). These qualitative differences suggest qualitative differences in carcinogenesis mechanisms. We hypothesize that the dominant mechanism for induction of many solid cancers by sparsely ionizing radiation is initiation of stem cells to a pre-malignant state, but for densely ionizing radiation the dominant mechanism is radiation-bystander-effect mediated promotion of already pre-malignant cell clone growth. Here we present a mathematical model based on these assumptions and test it using data on the incidence of dysplastic growths and tumors in the mammary glands of mice exposed to high or low dose rates of γ-rays and neutrons, either with or without pre-treatment with the chemical carcinogen 7,12-dimethylbenz-alpha-anthracene (DMBA). The model provides a mechanistic and quantitative explanation which is consistent with the data and may provide useful insight into human carcinogenesis. PMID:22194850

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.

Biological effects of low energy nitrogen ion implantation on Jatropha curcas L. seed germination

NASA Astrophysics Data System (ADS)

Xu, Gang; Wang, Xiao-teng; Gan, Cai-ling; Fang, Yan-qiong; Zhang, Meng

2012-09-01

To explore the biological effects of nitrogen ion beam implantation on dry Jatropha curcas seed, a beam of N+ with energy of 25 keV was applied to treat the dry seed at six different doses. N+ beam implantation greatly decreased germination rate and seedling survival rate. The doses within the range of 12 × 1016 to 15 × 1016 ions cm-2 severely damaged the seeds: total antioxidant capacity (TAC), germination rate, seedling survival rate, reduced ascorbate acid (HAsA) and reduced glutathione (GSH) contents, and most of the tested antioxidases activity (i.e. catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD)) reached their lowest levels. At a dose of 18 × 1016 ion cm-2, biological repair took place: moderate increases were found in TAC, germination rate, seedling survival rate, HAsA and GSH contents, and some antioxidant enzyme activities (i.e. CAT, APX, SOD and GPX). The dose of 18 × 1016 ions cm-2 may be the optimum dose for use in dry J. curcas seed mutation breeding. CAT, HAsA and GSH contributed to the increase of TAC, but CAT was the most important. POD performed its important role as seed was severely damaged. The main role of the HAsA-GSH cycle appeared to be for regeneration of HAsA.

Experimental and theoretical studies of nuclear generation of ozone from oxygen and oxygen-sulfur hexafluoride mixtures

NASA Astrophysics Data System (ADS)

Elsayed-Ali, H. E.; Miley, G. H.

1986-08-01

A series of experimental measurements of the yield of O3 in nuclear-induced O2 and O2-SF6 discharges are reported. The discharges were created by bombardment with energetic particles from the 10B(n,α)7Li reaction. Continuous irradiation at dose rates of 1015-1017 eV cm-3 s-1 and pulsed irradiation (˜10 ms FWHM) at a peak dose rate of ˜1020 eV cm-3 s-1 were conducted. At the lower dose rates, the addition of SF6 generally increased the ozone yield due to the slowing of ozone destruction by negative oxygen and ozone ions. In contrast, at the high dose rates, the ozone concentration decreased due to SF6 suppression of atomic oxygen formation by ion-ion recombination. A numerical model was developed and tested against experimental conditions. This model indicates that the steady-state ozone concentration was limited by the reaction O-3+O3→2O2+O-2 with a rate coefficient of ˜1×10-12 cm3 s-1. In addition to dose rate effects, pressure and temperature effects on ozone production are discussed and methods for increasing the ozone yield are suggested.

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.

Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation.

PubMed

Tran, Van; Little, Mark P

2017-11-01

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and non-malignant, show downward curvature in the dose response, and for most endpoints this is statistically significant (p < 0.05). Associated with this, the low-dose extrapolation factor associated with neutron exposure is generally statistically significantly less than 1 for most malignant and non-malignant endpoints, with central estimates mostly in the range 0.1-0.9. In contrast to the situation at higher dose rates, there are statistically non-significant decreases of risk per unit dose at gamma dose rates of less than or equal to 5 mGy/h for most malignant endpoints, and generally non-significant increases in risk per unit dose at gamma dose rates ≤5 mGy/h for most non-malignant endpoints. Associated with this, the dose-rate extrapolation factor, the ratio of high dose-rate to low dose-rate (≤5 mGy/h) gamma dose response slopes, for many tumour sites is in the range 1.2-2.3, albeit not statistically significantly elevated from 1, while for most non-malignant endpoints the gamma dose-rate extrapolation factor is less than 1, with most estimates in the range 0.2-0.8. After neutron exposure there are non-significant indications of lower risk per unit dose at dose rates ≤5 mGy/h compared to higher dose rates for most malignant endpoints, and for all tumours (p = 0.001), and respiratory tumours (p = 0.007) this reduction is conventionally statistically significant; for most non-malignant outcomes risks per unit dose non-significantly increase at lower dose rates. Associated with this, the neutron dose-rate extrapolation factor is less than 1 for most malignant and non-malignant endpoints, in many cases statistically significantly so, with central estimates mostly in the range 0.0-0.2.

The use of preoperative aspirin in cardiac surgery: A systematic review and meta-analysis.

PubMed

Aboul-Hassan, Sleiman Sebastian; Stankowski, Tomasz; Marczak, Jakub; Peksa, Maciej; Nawotka, Marcin; Stanislawski, Ryszard; Kryszkowski, Bartosz; Cichon, Romuald

2017-12-01

Despite the fact that aspirin is of benefit to patients following coronary artery bypass grafting (CABG), continuation or administration of preoperative aspirin before CABG or any cardiac surgical procedure remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the influence of preoperative aspirin administration on patients undergoing cardiac surgery. Medline database was searched using OVID SP interface. Similar searches were performed separately in EMBASE, PubMed, and Cochrane Central Registry of Controlled Trials. Twelve randomized controlled trials and 28 observational studies met our inclusion criteria and were included in the meta-analysis. The use of preoperative aspirin in patients undergoing CABG at any dose is associated with reduced early mortality as well as a reduced incidence of postoperative acute kidney injury (AKI). Low-dose aspirin (≤160 mg/d) is associated with a decreased incidence of perioperative myocardial infarction (MI). Administration of preoperative aspirin at any dose in patients undergoing cardiac surgery increases postoperative bleeding. Despite this effect of preoperative aspirin, it did not increase the rates of surgical re-exploration due to excessive postoperative bleeding nor did it increase the rates of packed red blood cell transfusions (PRBC) when preoperative low-dose aspirin (≤160 mg/d) was administered. Preoperative aspirin increases the risk for postoperative bleeding. However, this did not result in an increased need for chest re-exploration and did not increase the rates of PRBC transfusion when preoperative low-dose (≤160 mg/d) aspirin was administered. Aspirin at any dose is associated with decreased mortality and AKI and low-dose aspirin (≤160 mg/d) decreases the incidence of perioperative MI. © 2017 Wiley Periodicals, Inc.

Low doses of glyphosate enhance growth, CO2 assimilation, stomatal conductance and transpiration in sugarcane and eucalyptus.

PubMed

Nascentes, Renan F; Carbonari, Caio A; Simões, Plinio S; Brunelli, Marcela C; Velini, Edivaldo D; Duke, Stephen O

2018-05-01

Sublethal doses of herbicides can enhance plant growth and stimulate other process, an effect known as hormesis. The magnitude of hormesis is dependent on the plant species, the herbicide and its dose, plant development stage and environmental parameters. Glyphosate hormesis is well established, but relatively little is known of the mechanism of this phenomenon. The objective of this study was to determine if low doses of glyphosate that cause growth stimulation in sugarcane and eucalyptus concomitantly stimulate CO 2 assimilation. Shoot dry weight in both species increased at both 40 and 60 days after application of 6.2 to 20.2 g a.e. ha -1 glyphosate. The level of enhanced shoot dry weight was 11 to 37%, depending on the time after treatment and the species. Concomitantly, CO 2 assimilation, stomatal conductance and transpiration were increased by glyphosate doses similar to those that caused growth increases. Glyphosate applied at low doses increased the dry weight of sugarcane and eucalyptus plants in all experiments. This hormetic effect was related to low dose effects on CO 2 assimilation rate, stomatal conductance and transpiration rate, indicating that low glyphosate doses enhance photosynthesis of plants. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha-emitting nuclides, uranium-233, plutonium-239 and amercium-241.

PubMed

Ellender, M; Harrison, J D; Pottinger, H; Thomas, J M

2001-01-01

To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues. Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques. Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7-6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4-2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U. For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow.

Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.

PubMed

Sarashina, Akiko; Koiwai, Kazuki; Seman, Leo J; Yamamura, Norio; Taniguchi, Atsushi; Negishi, Takahiro; Sesoko, Shogo; Woerle, Hans J; Dugi, Klaus A

2013-01-01

This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN TUNGSTEN

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

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.

2015-04-16

We used our recently developed lattice-based object kinetic Monte Carlo code; KSOME [1] to carryout simulations of radiation damage in bulk tungsten at temperatures of 300, and 2050 K for various dose rates. Displacement cascades generated from molecular dynamics (MD) simulations for PKA energies at 60, 75 and 100 keV provided residual point defect distributions. It was found that the number density of vacancies in the simulation box does not change with dose rate while the number density of vacancy clusters slightly decreases with dose rate indicating that bigger clusters are formed at larger dose rates. At 300 K, althoughmore » the average vacancy cluster size increases slightly, the vast majority of vacancies exist as mono-vacancies. At 2050 K no accumulation of defects was observed during irradiation over a wide range of dose rates for all PKA energies studied in this work.« less

Ion-recombination correction for different ionization chambers in high dose rate flattening-filter-free photon beams

NASA Astrophysics Data System (ADS)

Lang, Stephanie; Hrbacek, Jan; Leong, Aidan; Klöck, Stephan

2012-05-01

Recently, there has been an increased interest in flattening-filter-free (FFF) linear accelerators. Removal of the filter results in available dose rates up to 24 Gy min-1 (for nominal energy 10 MV in depth of maximum dose, a source-surface distance of 100 cm and a field size of 10×10 cm2). To guarantee accurate relative and reference dosimetry for the FFF beams, we investigated the charge collection efficiency of multiple air-vented and one liquid ionization chamber for dose rates up to 31.9 Gy min-1. For flattened beams, the ion-collection efficiency of all air-vented ionization chambers (except for the PinPoint chamber) was above 0.995. By removing the flattening filter, we found a reduction in collection efficiency of approximately 0.5-0.9% for a 10 MV beam. For FFF beams, the Markus chamber showed the largest collection efficiency of 0.994. The observed collection efficiencies were dependent on dose per pulse, but independent of the pulse repetition frequency. Using the liquid ionization chamber, the ion-collection efficiency for flattened beams was above 0.990 for all dose rates. However, this chamber showed a low collection efficiency of 0.940 for the FFF 10 MV beam at a dose rate of 31.9 Gy min-1. All investigated air-vented ionization chambers can be reliably used for relative dosimetry of FFF beams. The order of correction for reference dosimetry is given in the manuscript. Due to their increased saturation in high dose rate FFF beams, liquid ionization chambers appear to be unsuitable for dosimetry within these contexts.

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

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

Jakobsen, Anders, E-mail: anders.jakobsen@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2012-11-15

Purpose: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. Methods and Materials: The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of {<=}5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; armmore » B). Concomitant chemotherapy, uftoral 300 mg/m{sup 2} and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). Results: The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). Conclusions: This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.« less

Commentary 2 to Cox and Little: radiation-induced oncogenic transformation: the interplay between dose, dose protraction, and radiation quality

NASA Technical Reports Server (NTRS)

Brenner, D. J.; Hall, E. J.

1992-01-01

There is now a substantial body of evidence for end points such as oncogenic transformation in vitro, and carcinogenesis and life shortening in vivo, suggesting that dose protraction leads to an increase in effectiveness relative to a single, acute exposure--at least for radiations of medium linear energy transfer (LET) such as neutrons. Table I contains a summary of the pertinent data from studies in which the effect is seen. [table: see text] This phenomenon has come to be known as the "inverse dose rate effect," because it is in marked contrast to the situation at low LET, where protraction in delivery of a dose of radiation, either by fractionation or low dose rate, results in a decreased biological effect; additionally, at medium and high LET, for radiobiological end points such as clonogenic survival, the biological effectiveness is independent of protraction. The quantity and quality of the published reports on the "inverse dose rate effect" leaves little doubt that the effect is real, but the available evidence indicates that the magnitude of the effect is due to a complex interplay between dose, dose rate, and radiation quality. Here, we first summarize the available data on the inverse dose rate effect and suggest that it follows a consistent pattern in regard to dose, dose rate, and radiation quality; second, we describe a model that predicts these features; and, finally, we describe the significance of the effect for radiation protection.

Charged particles radiation measurements with Liulin-MO dosimeter of FREND instrument aboard ExoMars Trace Gas Orbiter during the transit and in high elliptic Mars orbit

NASA Astrophysics Data System (ADS)

Semkova, Jordanka; Koleva, Rositza; Benghin, Victor; Dachev, Tsvetan; Matviichuk, Yuri; Tomov, Borislav; Krastev, Krasimir; Maltchev, Stephan; Dimitrov, Plamen; Mitrofanov, Igor; Malahov, Alexey; Golovin, Dmitry; Mokrousov, Maxim; Sanin, Anton; Litvak, Maxim; Kozyrev, Andrey; Tretyakov, Vladislav; Nikiforov, Sergey; Vostrukhin, Andrey; Fedosov, Fedor; Grebennikova, Natalia; Zelenyi, Lev; Shurshakov, Vyacheslav; Drobishev, Sergey

2018-03-01

ExoMars is a joint ESA-Rosscosmos program for investigating Mars. Two missions are foreseen within this program: one consisting of the Trace Gas Orbiter (TGO), that carries scientific instruments for the detection of trace gases in the Martian atmosphere and for the location of their source regions, plus an Entry, Descent and landing demonstrator Module (EDM), launched on March 14, 2016; and the other, featuring a rover and a surface platform, with a launch date of 2020. On October 19, 2016 TGO was inserted into high elliptic Mars' orbit. The dosimetric telescope Liulin-MO for measuring the radiation environment onboard the ExoMars 2016 TGO is a module of the Fine Resolution Epithermal Neutron Detector (FREND). Here we present first results from measurements of the charged particle fluxes, dose rates, Linear Energy Transfer (LET) spectra and estimation of dose equivalent rates in the interplanetary space during the cruise of TGO to Mars and first results from dosimetric measurements in high elliptic Mars' orbit. A comparison is made with the dose rates obtained by RAD instrument onboard Mars Science Laboratory during the cruise to Mars in 2011-2012 and with the Galactic Cosmic Rays (GCR) count rates provided by other particle detectors currently in space. The average measured dose rate in Si from GCR during the transit to Mars for the period April 22-September 15, 2016 is 372 ± 37 μGy d-1 and 390 ± 39 μGy d-1 in two perpendicular directions. The dose equivalent rate from GCR for the same time period is about 2 ± 0.3 mSv d-1. This is in good agreement with RAD results for radiation dose rate in Si from GCR in the interplanetary space, taking into account the different solar activity during the measurements of both instruments. About 10% increase of the dose rate, and 15% increase of the dose equivalent rate for 10.5 months flight is observed. It is due to the increase of Liulin-MO particle fluxes for that period and corresponds to the overall GCR intensity increase during the declining phase of the solar activity. Data show that during the cruise to Mars and back (6 months in each direction), taken during the declining of solar activity, the crewmembers of future manned flights to Mars will accumulate at least 60% of the total dose limit for the cosmonaut's/astronaut's career in case their shielding conditions are close to the average shielding of Liulin-MO detectors-about 10 g cm-2. The dosimetric measurements in high elliptic Mars' orbit demonstrate strong dependence of the GCR fluxes near the TGO pericenter on satellite's field of view shadowed by Mars.

The effect of low dose rate irradiation on the tensile properties and microstructure of austenitic stainless steel.

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

Allen, T. R.; Tsai, H.; Cole, J. I.

2002-09-17

To assess the effects of long-term, low-dose-rate neutron exposure on mechanical strength and ductility, tensile properties were measured on 12% and 20% cold-worked Type 316 stainless steel. Samples were prepared from reactor core components retrieved from the EBR-II reactor following final shutdown. Sample locations were chosen to cover a dose range of 1-56 dpa at temperatures from 371-440 C and dose rates from 0.5-5.8 x10{sup -7} dpa/s. These dose rates are approximately an order of magnitude lower than those of typical EBR-II test sample locations. The tensile tests for the 12% CW material were performed at 380 C and 430more » C while those for the 20% CW samples were performed at 370 C. In each case, the tensile test temperature approximately matched the irradiation temperature. To help understand the tensile properties, microstructural samples with similar irradiation history were also examined. The strength and loss of work hardening increase the fastest as a function of irradiation dose for the 12% CW material irradiated at lower temperature. The decrease in ductility with increasing dose occurs more rapidly for the 12% CW material irradiated at lower temperature and the 20% cold-worked material. Post-tensile test fractography indicates that at higher dose, the 20% CW samples begin a shift in fracture mode from purely ductile to mainly small facets and slip bands, suggesting a transition toward channel fracture. The fracture for all of the 12% cold-worked samples was ductile. For both the 12% and 20% CW materials, the yield strength increases correlate with changes in void and loop density and size.« less

Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

PubMed

Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

2016-07-01

Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration.

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg.

PubMed

Abadelah, Mohamad; Chrystyn, Henry; Bagherisadeghi, Golshan; Abdalla, Gaballa; Larhrib, Hassan

2018-01-01

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.

PubMed

Lin, Jin Xin; Krishna, Sanjeev; Su'a, Bruce; Hill, Andrew G

2016-09-01

Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites. This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen. A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015. All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria. The interventions used were various doses of botulinum toxin. Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals. There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined. This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented. Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.

Pharmacological doses of dietary curcumin increase colon epithelial cell proliferation in vivo in rats.

PubMed

Kim, Sylvia Jeewon; Hellerstein, Marc K

2007-10-01

Although curcumin has preventive actions in animal models of colon cancer, whether the mechanism of action is through anti-proliferation in normal environment is not clearly understood. Here, we studied the effects of chemopreventive doses of curcumin on the proliferation rate of colon epithelial cells (CEC), using a recently developed stable isotope-mass spectrometric method for measuring DNA synthesis rate. Adult male F344 rats were given diets containing 0, 2 and 4% curcumin for 5 weeks. 4% (2)H(2)O was given in drinking water to label DNA, after a priming bolus, for 4 days prior to sacrifice. The isotopic enrichment of the deoxyribose moiety of deoxyadenosine from DNA was measured by gas chromatography - mass spectrometry. Cell cycle analysis was performed after propidium iodide staining of CECs. Curcumin administration did not reduce but instead resulted in dose-dependent increases in CEC proliferation rate (p < 0.05) for 2% and 4% curcumin vs 0%). The length of the colon crypts and the fraction of cells in S-phase were also increased in the 2% and 4% curcumin groups (p < 0.05). Thus, pharmacological doses of curcumin increase CEC proliferation rate and pool size in normal rats. Reduction of CEC proliferation therefore cannot explain the proposed chemopreventive actions of curcumin in colon cancer.

Contributions of Various Radiological Sources to Background in a Suburban Environment

DOE PAGES

Milvenan, Richard D.; Hayes, Robert B.

2016-11-01

This work is a brief overview and comparison of dose rates stemming from both indoor and outdoor natural background radiation and household objects within a suburban environment in North Carolina. Combined gamma and beta dose rates were taken from indoor objects that ranged from the potassium in fruit to the americium in smoke detectors. For outdoor measurements, various height and time data samples were collected to show fluctuations in dose rate due to temperature inversion and geometric attenuation. Although each sample tested proved to have a statistically significant increase over background using Students t-test, no sample proved to be moremore » than a minor increase in natural radiation dose. Furthermore, the relative contributions from natural radioactivity such as potassium in foods and common household items are shown to be easily distinguished from background using standard handheld instrumentation when applied in a systematic, methodological manner.« less

Contributions of Various Radiological Sources to Background in a Suburban Environment

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

Milvenan, Richard D.; Hayes, Robert B.

This work is a brief overview and comparison of dose rates stemming from both indoor and outdoor natural background radiation and household objects within a suburban environment in North Carolina. Combined gamma and beta dose rates were taken from indoor objects that ranged from the potassium in fruit to the americium in smoke detectors. For outdoor measurements, various height and time data samples were collected to show fluctuations in dose rate due to temperature inversion and geometric attenuation. Although each sample tested proved to have a statistically significant increase over background using Students t-test, no sample proved to be moremore » than a minor increase in natural radiation dose. Furthermore, the relative contributions from natural radioactivity such as potassium in foods and common household items are shown to be easily distinguished from background using standard handheld instrumentation when applied in a systematic, methodological manner.« less

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

PubMed

van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

2017-12-01

Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8-10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). T.C.T., H.L.T. and S.C.O. received an unrestricted personal grant from Merck BV. H.R.V. receives monetary compensation as a member on an external advisory board for Ferring pharmaceutical BV. B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. F.J.M.B. receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number NTR2657. 20 December 2010. 12 May 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

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.

Safety of an i.v. β-adrenergic blockade protocol for heart rate optimization before coronary CT angiography.

PubMed

Kassamali, Rahil H; Kim, Daniel H; Patel, Hiten; Raichura, Nitin; Hoey, Edward T D; Hodson, James; Hussain, Shahid

2014-10-01

The purpose of this study was to assess the safety of heart rate optimization by use of β-adrenergic blockade solely by the i.v. route before coronary CT angiography. The records of 679 patients undergoing CT coronary angiography after receiving i.v. β-adrenergic blockade were retrospectively analyzed. Health screening was completed before scanning, and heart rate was optimized by administration of i.v. metoprolol titrated to a maximum of 70 mg to achieve a heart rate less than 65 beats/min. The median i.v. dose was 20 mg (range, 5-70 mg). The 679 patients analyzed had a total of 10 complications (1.47%). Major complications, defined as not resolving with observation and analgesia alone, occurred in only three patients (0.44%). These complications included a second-degree atrioventricular block. A total of 299 patients (44.0%) needed more than 20 mg of i.v. metoprolol to achieve target heart rate. Only three patients needed the maximum i.v. dose of 70 mg metoprolol. Target heart rate was reached successfully in 666 patients (98.1%) with doses of less than 70 mg. This study did not show a statistically significant association between increasing complication frequency and increasing dose. This study showed that high doses of i.v. metoprolol can be used effectively and with a low rate of major complications to control heart rate before coronary CT angiography in correctly screened patients.

Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II

NASA Technical Reports Server (NTRS)

Pecaut, Michael J.; Gridley, Daila S.; Smith, Anna L.; Nelson, Gregory A.

2002-01-01

The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.

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

PubMed

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

2003-02-01

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

SU-F-T-322: A Comparison of Two Si Detectors for in Vivo Dosimetry

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

Talarico, O; Krylova, T; Lebedenko, I

Purpose: To compare two types of semiconductor detectors for in vivo dosimetry by their dependence from various parameters in different conditions. Methods: QED yellow (Sun Nuclear) and EDP (Scanditronix) Si detectors were radiated by a Varian Clinac 2300 ix with 6 and 18 MV energies. 10 cm thickness water equivalent phantom consisted of 30×30 cm{sup 2} squared plates was used for experiments. Dose dependencies for different beam angles (0 – 180°), field size (3–40 cm), dose (50 – 300 MU), and dose rates (50 – 300 MU/min) were obtained and calibrated with Standard Farmer chamber (PTW). Results: Reproducibility, linearity, dosemore » rate, angular dependence, and field size dependence were obtained for QED and EDP. They show no dose-rate dependence in available clinical dose rate range (100–600 MU/min). Both diodes have linear dependence with increasing the dose. Therefore even in case of high radiation therapy (including total body irradiation) it is not necessary to apply an additional correction during in vivo dosimetry. The diodes have different behavior for angular and field size dependencies. QED diode showed that dose value is stable for beam angles from 0 to 60°, for 60–180° correction factor has to be applied for each beam angle during in vivo measurements. For EDP diode dose value is sensitive to beam angle in whole range of angles. Conclusion: The study shows that QED diode is more suitable for in vivo dosimetry due to dose value independence from incident beam angle in the range 0–60°. There is no need in correction factors for increasing of dose and dose rate for both diodes. The next step will be to carry out measurements in non-standard conditions of total body irradiation. After this modeling of these experiments with Monte Carlo simulation for comparison calculated and obtained data is planned.« less

Seasonal regulation of condensed tannin consumption by free-ranging goats in a semi-arid savanna

PubMed Central

Heitkӧnig, Ignas M. A.; Scogings, Peter F.; Hattas, Dawood; Dziba, Luthando E.; Prins, Herbert H. T.; de Boer, Willem F.

2018-01-01

Although condensed tannins (CTs) are known to reduce forage intake by mammalian herbivores in controlled experiments, few studies have tested these effects in the field. Thus the role of CTs on foraging ecology of free-ranging herbivores is inadequately understood. To investigate the effects of CTs under natural savanna conditions, we pre-dosed groups of goats with polyethylene glycol (PEG, a CT-neutralising chemical), CT powder or water before observing their foraging behaviour. While accounting for the effects of season and time of the day, we tested the hypothesis that herbivores forage in ways that reduce the intake rate (g DM per minute) of CTs. We expected pre-dosing goats with CTs to reduce CT intake rates by (1) consuming diets low in CTs, (2) reducing bite rates, (3) increasing the number of foraging bouts, or (4) reducing the length of foraging bouts. Lastly, (5) expected CT to have no influence the number of dietary forage species. In both wet and dry seasons, pre-dosing goats with CTs resulted in lower CT consumption rates compared to PEG goats which seemed relieved from the stress associated with CT consumption. During dry season, the number of dietary forage species was similar across treatments, although goats that were dosed with PEG significantly increased this number in the wet season. Dosing goats with PEG increased the number and length of browsing bouts compared to goats from the other treatments. Pre-loading goats with PEG also tended to increase bite rates on browse forages, which contributed to increased consumption rates of CTs. Based on the behavioural adjustments made by goats in this study and within the constraints imposed by chemical complexity in savanna systems, we concluded that herbivores under natural conditions foraged in ways that minimised CTs consumption. More research should further elucidate the mechanism through which CTs regulated feeding behaviour. PMID:29293513

Radiation dose rates now and in the future for residents neighboring restricted areas of the Fukushima Daiichi Nuclear Power Plant

PubMed Central

Harada, Kouji H.; Niisoe, Tamon; Imanaka, Mie; Takahashi, Tomoyuki; Amako, Katsumi; Fujii, Yukiko; Kanameishi, Masatoshi; Ohse, Kenji; Nakai, Yasumichi; Nishikawa, Tamami; Saito, Yuuichi; Sakamoto, Hiroko; Ueyama, Keiko; Hisaki, Kumiko; Ohara, Eiji; Inoue, Tokiko; Yamamoto, Kanako; Matsuoka, Yukiyo; Ohata, Hitomi; Toshima, Kazue; Okada, Ayumi; Sato, Hitomi; Kuwamori, Toyomi; Tani, Hiroko; Suzuki, Reiko; Kashikura, Mai; Nezu, Michiko; Miyachi, Yoko; Arai, Fusako; Kuwamori, Masanori; Harada, Sumiko; Ohmori, Akira; Ishikawa, Hirohiko; Koizumi, Akio

2014-01-01

Radiation dose rates were evaluated in three areas neighboring a restricted area within a 20- to 50-km radius of the Fukushima Daiichi Nuclear Power Plant in August–September 2012 and projected to 2022 and 2062. Study participants wore personal dosimeters measuring external dose equivalents, almost entirely from deposited radionuclides (groundshine). External dose rate equivalents owing to the accident averaged 1.03, 2.75, and 1.66 mSv/y in the village of Kawauchi, the Tamano area of Soma, and the Haramachi area of Minamisoma, respectively. Internal dose rates estimated from dietary intake of radiocesium averaged 0.0058, 0.019, and 0.0088 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. Dose rates from inhalation of resuspended radiocesium were lower than 0.001 mSv/y. In 2012, the average annual doses from radiocesium were close to the average background radiation exposure (2 mSv/y) in Japan. Accounting only for the physical decay of radiocesium, mean annual dose rates in 2022 were estimated as 0.31, 0.87, and 0.53 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. The simple and conservative estimates are comparable with variations in the background dose, and unlikely to exceed the ordinary permissible dose rate (1 mSv/y) for the majority of the Fukushima population. Health risk assessment indicates that post-2012 doses will increase lifetime solid cancer, leukemia, and breast cancer incidences by 1.06%, 0.03% and 0.28% respectively, in Tamano. This assessment was derived from short-term observation with uncertainties and did not evaluate the first-year dose and radioiodine exposure. Nevertheless, this estimate provides perspective on the long-term radiation exposure levels in the three regions. PMID:24567380

Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.

PubMed

Belke, T W; Oldford, A C; Forgie, M Y; Beye, J A

2005-07-01

The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.

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.

Differences in rates of decrease of environmental radiation dose rates by ground surface property in Fukushima City after the Fukushima Daiichi nuclear power plant accident.

PubMed

Kakamu, Takeyasu; Kanda, Hideyuki; Tsuji, Masayoshi; Kobayashi, Daisuke; Miyake, Masao; Hayakawa, Takehito; Katsuda, Shin-ichiro; Mori, Yayoi; Okouchi, Toshiyasu; Hazama, Akihiro; Fukushima, Tetsuhito

2013-01-01

After the Great East Japan Earthquake on 11 March 2011, the environmental radiation dose in Fukushima City increased. On 11 April, 1 mo after the earthquake, the environmental radiation dose rate at various surfaces in the same area differed greatly by surface property. Environmental radiation measurements continue in order to determine the estimated time to 50% reduction in environmental radiation dose rates by surface property in order to make suggestions for decontamination in Fukushima. The measurements were carried out from 11 April to 11 November 2011. Forty-eight (48) measurement points were selected, including four kinds of ground surface properties: grass (13), soil (5), artificial turf (7), and asphalt (23). Environmental radiation dose rate was measured at heights of 100 cm above the ground surface. Time to 50% reduction of environmental radiation dose rates was estimated for each ground surface property. Radiation dose rates on 11 November had decreased significantly compared with those on 11 April for all surface properties. Artificial turf showed the longest time to 50% reduction (544.32 d, standard error: 96.86), and soil showed the shortest (213.20 d, standard error: 35.88). The authors found the environmental radiation dose rate on artificial materials to have a longer 50% reduction time than that on natural materials. These results contribute to determining an order of priority for decontamination after nuclear disasters.

Overdose and prescribed opioids: Associations among chronic non-cancer pain patients

PubMed Central

Dunn, Kate M; Saunders, Kathleen W; Rutter, Carolyn M; Banta-Green, Caleb J; Merrill, Joseph O; Sullivan, Mark D; Weisner, Constance M; Silverberg, Michael J; Campbell, Cynthia I; Psaty, Bruce M; Von Korff, Michael

2010-01-01

Background Chronic opioid therapy for chronic non-cancer pain (CNCP) is increasingly common in community practice. Concomitant with this practice change, rates of fatal opioid overdose have increased. It is not known to what extent overdose risks are elevated among patients receiving medically prescribed chronic opioid therapy. Objective To estimate rates of opioid overdose and their association with average prescribed daily opioid dose among patients receiving medically prescribed chronic opioid therapy. Design Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at time of overdose. Setting Health maintenance organization. Patients Individuals (n=9940) who received 3+ opioid prescriptions within 90-days for CNCP between 1997 and 2005. Measurements Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes, non-fatal and fatal overdoses, were identified through diagnostic codes from inpatient and outpatient care and death certificates and confirmed by medical record review. Results Fifty-one opioid-related overdoses were identified, including six deaths. Compared to patients receiving 1-20mg of opioids per day (0.2% annual overdose rate), patients receiving 50-99 mg had a 3.7 fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7% annual overdose rate. Patients receiving 100mg or more per day had an 8.9 fold increase in overdose risk (95% C.I. 4.0, 19.7) and a 1.8% annual overdose rate. Limitations Increased overdose risk among patients on higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation. Conclusions Patients receiving higher doses of prescribed opioids are at increased risk of opioid overdose, underscoring the need for close supervision of these patients. PMID:20083827

Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows.

PubMed

Laporta, Jimena; Moore, Spencer A E; Weaver, Samantha R; Cronick, Callyssa M; Olsen, Megan; Prichard, Austin P; Schnell, Brian P; Crenshaw, Thomas D; Peñagaricano, Francisco; Bruckmaier, Rupert M; Hernandez, Laura L

2015-07-01

A 4×4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-l-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre- and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre- and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (βHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism. © 2015 Society for Endocrinology.

Chromosomal Aberrations in Wild Mice Captured in Areas Differentially Contaminated by the Fukushima Dai-Ichi Nuclear Power Plant Accident.

PubMed

Kubota, Yoshihisa; Tsuji, Hideo; Kawagoshi, Taiki; Shiomi, Naoko; Takahashi, Hiroyuki; Watanabe, Yoshito; Fuma, Shoichi; Doi, Kazutaka; Kawaguchi, Isao; Aoki, Masanari; Kubota, Masahide; Furuhata, Yoshiaki; Shigemura, Yusaku; Mizoguchi, Masahiko; Yamada, Fumio; Tomozawa, Morihiko; Sakamoto, Shinsuke H; Yoshida, Satoshi

2015-08-18

Following the Fukushima Dai-ichi Nuclear Power Plant accident, radiation effects on nonhuman biota in the contaminated areas have been a great concern. The induction of chromosomal aberrations in splenic lymphocytes of small Japanese field mice (Apodemus argenteus) and house mice (Mus musculus) inhabiting Fukushima Prefecture was investigated. In mice inhabiting the slightly contaminated area, the average frequency of dicentric chromosomes was similar to that seen in mice inhabiting a noncontaminated control area. In contrast, mice inhabiting the moderately and heavily contaminated areas showed a significant increase in the average frequencies of dicentric chromosomes. Total absorbed dose rate was estimated to be approximately 1 mGy d(-1) and 3 mGy d(-1) in the moderately and heavily contaminated areas, respectively. Chromosomal aberrations tended to roughly increase with dose rate. Although theoretically, the frequency of chromosomal aberrations was considered proportional to the absorbed dose, chromosomal aberrations in old mice (estimated median age 300 days) did not increase with radiation dose at the same rate as that observed in young mice (estimated median age 105 days).

Vascular dilation, tachycardia, and increased inotropy occur sequentially with increasing epinephrine dose rate, plasma and myocardial concentrations, and cAMP

PubMed Central

Maslov, Mikhail Y.; Wei, Abraham E.; Pezone, Matthew J.; Edelman, Elazer R.; Lovich, Mark A.

2015-01-01

Background While epinephrine infusion is widely used in critical care for inotropic support, there is no direct method to detect the onset and measure the magnitude of this response. We hypothesized that surrogate measurements, such as heart rate and vascular tone, may indicate if the plasma and tissue concentrations of epinephrine and cAMP are in a range sufficient to increase myocardial contractility. Methods Cardiovascular responses to epinephrine infusion (0.05–0.5 mcg·kg−1·min−1) were measured in rats using arterial and left ventricular catheters. Epinephrine and cAMP levels were measured using ELISA techniques. Results The lowest dose of epinephrine infusion (0.05 mcg·kg−1·min−1) did not raise plasma epinephrine level and did not lead to cardiovascular response. Incremental increase in epinephrine infusion (0.1 mcg·kg−1·min−1) elevated plasma but not myocardial epinephrine levels, providing vascular, but not cardiac effects. Further increase in the infusion rate (0.2 mcg·kg−1·min−1) raised myocardial tissue epinephrine levels sufficient to increase heart rate but not contractility. Inotropic and lusitropic effects were significant at the infusion rate of 0.3 mcg·kg−1·min−1. Correlation of plasma epinephrine to hemodynamic parameters suggest that as plasma concentration increases, systemic vascular resistance falls (EC50=47 pg/ml), then HR increases (ED50=168 pg/ml), followed by a rise in contractility and lusitropy (ED50=346 pg/ml and ED50=324 pg/ml accordingly). Conclusions The dose response of epinephrine is distinct for vascular tone, HR and contractility. The need for higher doses to see cardiac effects is likely due to the threshold for drug accumulation in tissue. Successful inotropic support with epinephrine cannot be achieved unless the infusion is sufficient to raise the heart rate. PMID:25790776

Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule.

PubMed

Anand, Abhijeet; Molodecky, Natalie A; Pallansch, Mark A; Sutter, Roland W

2017-05-19

The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19-42% (median: 37%, p<0.001) and relative increase of 53-125% (median: 82%), and antibody titer to type 2 increasing by 2-32-fold (median: 10-fold). Early age of administration and shorter intervals between doses were associated with lower immunogenicity. Overall, two fIPV doses are more immunogenic than a single full-dose, associated with significantly increased seroconversion rates and antibody titers. Two fIPV doses together use two-fifth of the vaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14weekshas been endorsed by technical oversight committees and has been introduced in some affected countries. Copyright © 2017. Published by Elsevier Ltd.

Total Dose Effects on Error Rates in Linear Bipolar Systems

NASA Technical Reports Server (NTRS)

Buchner, Stephen; McMorrow, Dale; Bernard, Muriel; Roche, Nicholas; Dusseau, Laurent

2007-01-01

The shapes of single event transients in linear bipolar circuits are distorted by exposure to total ionizing dose radiation. Some transients become broader and others become narrower. Such distortions may affect SET system error rates in a radiation environment. If the transients are broadened by TID, the error rate could increase during the course of a mission, a possibility that has implications for hardness assurance.

Time-resolved in vivo luminescence dosimetry for online error detection in pulsed dose-rate brachytherapy.

PubMed

Andersen, Claus E; Nielsen, Søren Kynde; Lindegaard, Jacob Christian; Tanderup, Kari

2009-11-01

The purpose of this study is to present and evaluate a dose-verification protocol for pulsed dose-rate (PDR) brachytherapy based on in vivo time-resolved (1 s time resolution) fiber-coupled luminescence dosimetry. Five cervix cancer patients undergoing PDR brachytherapy (Varian GammaMed Plus with 192Ir) were monitored. The treatments comprised from 10 to 50 pulses (1 pulse/h) delivered by intracavitary/interstitial applicators (tandem-ring systems and/or needles). For each patient, one or two dosimetry probes were placed directly in or close to the tumor region using stainless steel or titanium needles. Each dosimeter probe consisted of a small aluminum oxide crystal attached to an optical fiber cable (1 mm outer diameter) that could guide radioluminescence (RL) and optically stimulated luminescence (OSL) from the crystal to special readout instrumentation. Positioning uncertainty and hypothetical dose-delivery errors (interchanged guide tubes or applicator movements from +/-5 to +/-15 mm) were simulated in software in order to assess the ability of the system to detect errors. For three of the patients, the authors found no significant differences (P>0.01) for comparisons between in vivo measurements and calculated reference values at the level of dose per dwell position, dose per applicator, or total dose per pulse. The standard deviations of the dose per pulse were less than 3%, indicating a stable dose delivery and a highly stable geometry of applicators and dosimeter probes during the treatments. For the two other patients, the authors noted significant deviations for three individual pulses and for one dosimeter probe. These deviations could have been due to applicator movement during the treatment and one incorrectly positioned dosimeter probe, respectively. Computer simulations showed that the likelihood of detecting a pair of interchanged guide tubes increased by a factor of 10 or more for the considered patients when going from integrating to time-resolved dose verification. The likelihood of detecting a +/-15 mm displacement error increased by a factor of 1.5 or more. In vivo fiber-coupled RL/OSL dosimetry based on detectors placed in standard brachytherapy needles was demonstrated. The time-resolved dose-rate measurements were found to provide a good way to visualize the progression and stability of PDR brachytherapy dose delivery, and time-resolved dose-rate measurements provided an increased sensitivity for detection of dose-delivery errors compared with time-integrated dosimetry.

Study of variations in structural, optical parameters and bulk etch rate of CR-39 polymer due to electron irradiation

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

Sahoo, G. S.; Joshi, D. S.; Tripathy, S. P., E-mail: sam.tripathy@gmail.com, E-mail: tripathy@barc.gov.in

2016-07-14

In this work, electron induced modifications on the bulk etch rate, structural and optical parameters of CR-39 polymer were studied using gravimetric, FTIR (Fourier Transform Infrared) and UV–vis (Ultraviolet–Visible) techniques, respectively. CR-39 samples were irradiated with 10 MeV electron beam for different durations to have the absorbed doses of 1, 10, 550, 5500, 16 500, and 55 000 kGy. From the FTIR analysis, the peak intensities at different bands were found to be changing with electron dose. A few peaks were observed to shift at high electron doses. From the UV-vis analysis, the optical band gaps for both direct and indirect transitions weremore » found to be decreasing with the increase in electron dose whereas the opacity, number of carbon atoms in conjugation length, and the number of carbon atoms per cluster were found to be increasing. The bulk etch rate was observed to be increasing with the electron dose. The primary objective of this investigation was to study the response of CR-39 to high electron doses and to determine a suitable pre-irradiation condition. The results indicated that, the CR-39 pre-irradiated with electrons can have better sensitivity and thus can be potentially applied for neutron dosimetry.« less

Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol.

PubMed

Rönn, O; Bengtsson, B; Edgar, B; Raner, S

1985-01-01

In a single-blind randomised study in 9 healthy men we compared the acute haemodynamic effects of the calcium antagonists felodipine and verapamil, singly and in combination with metoprolol. Three different cumulative intravenous doses of 0.25, 0.75 and 1.5 mg felodipine and of 2.0, 4.0 and 8.0 mg verapamil or placebo were given as constant infusions over 5 minutes on 3 occasions and were followed by intravenous metoprolol (15 mg). Felodipine caused a significant and dose-dependent decrease in the total peripheral resistance, and an increase in the forearm blood flow by 8, 48 and 163% with progressively increasing doses showing that the drug is a potent arteriolar vasodilator. A significant and dose-dependent increase in heart rate and a decrease in the pre-ejection period/left ventricular ejection time (PEP/LVET) ratio of up to 15% was also recorded, mainly reflecting a reflexogenic increase in the sympathetic tone. Total peripheral resistance, forearm blood flow, heart rate and the systolic time intervals were mainly unchanged after verapamil, whereas the PQ interval was prolonged. Metoprolol given after the 2 calcium antagonists caused a decrease in heart rate and blood flow and an increase in the total peripheral resistance and PEP/LVET ratio. The tolerability was good to all infusions.

Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using 125I seeds

PubMed Central

Wang, Zhong-Min; Lu, Jian; Zhang, Li-Yun; Lin, Xiao-Zhu; Chen, Ke-Min; Chen, Zhi-Jin; Liu, Fen-Ju; Yan, Fu-Hua; Teng, Gao-Jun; Mao, Ai-Wu

2015-01-01

AIM: To determine the mechanism of the radiation-induced biological effects of 125I seeds on pancreatic carcinoma cells in vitro. METHODS: SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment. Gray’s model of iodine-125 (125I) seed irradiation was used. In vitro, exponential phase SW1990, and PANC-1 cells were exposed to 0, 2, 4, 6, and 8 Gy using 125I radioactive seeds, with an initial dose rate of 12.13 cGy/h. A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies. Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells. DNA synthesis was measured via a tritiated thymidine (3H-TdR) incorporation experiment. After continuous low-dose-rate irradiation with 125I radioactive seeds, the survival fractions at 2 Gy (SF2), percentage apoptosis, and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared. RESULTS: The survival fractions of the PANC-1 and SW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased. No significant difference in SF2 was observed between SW1990 and PANC-1 cells (0.766 ± 0.063 vs 0.729 ± 0.045, P < 0.05). The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990 and PANC-1 cells. The rate of apoptosis increased with increasing radiation dosage. The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells. Dose-dependent G2/M cell-cycle arrest was observed after 125I seed irradiation, with a peak value at 6 Gy. As the dose increased, the percentage of G2/M cell cycle arrest increased in both cell lines, whereas the rate of DNA incorporation decreased. In the 3H-TdR incorporation experiment, the dosimetry results of both the SW1990 and PANC-1 cells decreased as the radiation dose increased, with a minimum at 6 Gy. There were no significant differences in the dosimetry results of the two cell lines when they were exposed to the same dose of radiation. CONCLUSION: The pancreatic cancer cell-killing effects induced by 125I radioactive seeds mainly occurred via apoptosis and G2/M cell cycle arrest. PMID:25741139

Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators.

PubMed

Wang, Jinghui; Trovati, Stefania; Borchard, Philipp M; Loo, Billy W; Maxim, Peter G; Fahrig, Rebecca

2017-12-01

To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs. The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz. For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 μs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500°C in our study. A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs. © 2017 American Association of Physicists in Medicine.

Low temperature neutron irradiation effects on microstructure and tensile properties of molybdenum

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

Li, Meimei; Eldrup, M.; Byun, Thak Sang

2008-01-01

Polycrystalline molybdenum was irradiated in the hydraulic tube facility at the High Flux Isotope Reactor to doses ranging from 7.2 x 10{sup -5} to 0.28 dpa at {approx} 80 C. As-irradiated microstructure was characterized by room-temperature electrical resistivity measurements, transmission electron microscopy (TEM) and positron annihilation spectroscopy (PAS). Tensile tests were carried out between -50 and 100 C over the strain rate range 1 x 10{sup -5} to 1 x 10{sup -2} s{sup -1}. Fractography was performed by scanning electron microscopy (SEM), and the deformation microstructure was examined by TEM after tensile testing. Irradiation-induced defects became visible by TEM atmore » {approx}0.001 dpa. Both their density and mean size increased with increasing dose. Submicroscopic three-dimensional cavities were detected by PAS even at {approx}0.0001 dpa. The cavity density increased with increasing dose, while their mean size and size distribution was relatively insensitive to neutron dose. It is suggested that the formation of visible dislocation loops was predominantly a nucleation and growth process, while in-cascade vacancy clustering may be significant in Mo. Neutron irradiation reduced the temperature and strain rate dependence of the yield stress, leading to radiation softening in Mo at lower doses. Irradiation had practically no influence on the magnitude and the temperature and strain rate dependence of the plastic instability stress.« less

Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope.

PubMed

Johnston-Peck, Aaron C; DuChene, Joseph S; Roberts, Alan D; Wei, Wei David; Herzing, Andrew A

2016-11-01

Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO 2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. Published by Elsevier B.V.

Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope

PubMed Central

Johnston-Peck, Aaron C.; DuChene, Joseph S.; Roberts, Alan D.; Wei, Wei David; Herzing, Andrew A.

2016-01-01

Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300 keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. PMID:27469265

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

PubMed

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells

PubMed Central

Neumaier, Teresa; Swenson, Joel; Pham, Christopher; Polyzos, Aris; Lo, Alvin T.; Yang, PoAn; Dyball, Jane; Asaithamby, Aroumougame; Chen, David J.; Bissell, Mina J.; Thalhammer, Stefan; Costes, Sylvain V.

2012-01-01

The concept of DNA “repair centers” and the meaning of radiation-induced foci (RIF) in human cells have remained controversial. RIFs are characterized by the local recruitment of DNA damage sensing proteins such as p53 binding protein (53BP1). Here, we provide strong evidence for the existence of repair centers. We used live imaging and mathematical fitting of RIF kinetics to show that RIF induction rate increases with increasing radiation dose, whereas the rate at which RIFs disappear decreases. We show that multiple DNA double-strand breaks (DSBs) 1 to 2 μm apart can rapidly cluster into repair centers. Correcting mathematically for the dose dependence of induction/resolution rates, we observe an absolute RIF yield that is surprisingly much smaller at higher doses: 15 RIF/Gy after 2 Gy exposure compared to approximately 64 RIF/Gy after 0.1 Gy. Cumulative RIF counts from time lapse of 53BP1-GFP in human breast cells confirmed these results. The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation. However, our discovery of DSB clustering over such large distances casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation. PMID:22184222

The relation between doses or post-plasma time points and apoptosis of leukemia cells induced by dielectric barrier discharge plasma

NASA Astrophysics Data System (ADS)

Wang, Chao; Zhang, Haixia; Xue, Zhixiao; Yin, Huijuan; Niu, Qing; Chen, Hongli

2015-12-01

The dielectric barrier discharge (DBD) plasma was applied to induce apoptosis of LT-12 leukemia cells. Plasma effects on cell death was evaluated by MTT assay and FCM apoptosis assay with Annexin V/PI double staining, suggesting that plasma killing cells rate and inducing cell apoptosis rate both positively were related to the plasma doses or the post-plasma time points. The cell death rates increased from 15.2% to 33.1% and the apoptosis rate raise from 23.8% to 28% when the dose raise from 60s to 120 s at 8 h post-plasma, while they increased from 15.4% to 34.9% and from 48% to 55.3% respectively at the same doses at 12 h post-plasma. Furthermore, the production of reactive oxygen species (ROS), gene and protein expression for Caspases and Bcl-2 family members were measured for exploring the related apoptotic mechanisms phenomenon. We found ROS immediately increased to 1.24 times of the original amount, then increasing to 5.39-fold at 20 h after treatment. The gene and protein expression for Caspases and Bcl-2 family members are very active at 8-12 h post-plasma. Our results demonstrate that DBD plasma can effectively induce tumor cell death through primarily related apoptotic mechanisms.

Biological effective dose for comparison and combination of external beam and low-dose rate interstitial brachytherapy prostate cancer treatment plans

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

Jani, Ashesh B.; Hand, Christopher M.; Lujan, Anthony E.

2004-03-31

We report a methodology for comparing and combining dose information from external beam radiotherapy (EBRT) and interstitial brachytherapy (IB) components of prostate cancer treatment using the biological effective dose (BED). On a prototype early-stage prostate cancer patient treated with EBRT and low-dose rate I-125 brachytherapy, a 3-dimensional dose distribution was calculated for each of the EBRT and IB portions of treatment. For each component of treatment, the BED was calculated on a point-by-point basis to produce a BED distribution. These individual BED distributions could then be summed for combined therapies. BED dose-volume histograms (DVHs) of the prostate, urethra, rectum, andmore » bladder were produced and compared for various combinations of EBRT and IB. Transformation to BED enabled computation of the relative contribution of each modality to the prostate dose, as the relative weighting of EBRT and IB was varied. The BED-DVHs of the prostate and urethra demonstrated dramatically increased inhomogeneity with the introduction of even a small component of IB. However, increasing the IB portion relative to the EBRT component resulted in lower dose to the surrounding normal structures, as evidenced by the BED-DVHs of the bladder and rectum. Conformal EBRT and low-dose rate IB conventional dose distributions were successfully transformed to the common 'language' of BED distributions for comparison and for merging prostate cancer radiation treatment plans. The results of this analysis can assist physicians in quantitatively determining the best combination and weighting of radiation treatment modalities for individual patients.« less

Analgesia/anesthesia for external cephalic version.

PubMed

Weiniger, Carolyn F

2013-06-01

Professional society guidelines recommend that women with breech presentation be delivered surgically due to a higher incidence of fetal risks compared with vaginal delivery. An alternative is attempted external cephalic version, which if successful, enables attempted vaginal delivery. Attitudes towards external cephalic version (ECV) will be considered in this review, along with pain relief methods and their impact on ECV success rates. Articles suggest that ECV is infrequently offered, due to both physician and patient factors. Success of ECV is higher in multiparous women, complete breech, posterior placenta, or smaller fetus. Preterm ECV performance does not increase vaginal delivery rates. Neuraxial techniques (spinal or epidural) significantly increase ECV success rates, as do moxibustion and hypnosis. Four reviews summarized studies considering ECV and neuraxial techniques. These reviews suggest that neuraxial techniques using high (surgical) doses of local anesthetic are efficacious compared with control groups not using anesthesia, whereas techniques using low-doses are not. Low-dose versus high-dose neuraxial analgesia/anesthesia has not been directly compared in a single study. Based on currently available data, the rate of cephalic presentation is not increased using neuraxial techniques, but vaginal delivery rates are higher. ECV appears to be a low-risk procedure. The logistics of routine ECV and provision of optimal neuraxial techniques for successful ECV require additional research. Safety aspects of neuraxial anesthesia for ECV require further investigation.

The effects of proton radiation on the prothrombin and partial thromboplastin times of irradiated ferrets

PubMed Central

Krigsfeld, Gabriel S.; Sanzari, Jenine K.; Kennedy, Ann R.

2013-01-01

Purpose To determine whether proton radiation affects coagulation. Material and methods Ferrets were exposed to solar particle event-like proton radiation at doses of 0, 25, 100, or 200 centigray (cGy), and dose rates of 50 cGy/minute (high dose rate or HDR) or 50 cGy/hour (low dose rate or LDR). Plasma was isolated from blood collected prior to radiation exposure and at 3–7 h post-radiation. Prothrombin time (PT) assays and activated partial thromboplastin time (aPTT) assays were performed as were mixing studies to determine the coagulation factors involved. Results HDR and LDR exposure led to statistically significant increases in PT values. It was determined that the HDR-induced increase in PT was due to Factor VII, while Factors II, V, and VII contributed to the LDR-induced increase in PT values. Only acute LDR exposure caused an increase in aPTT values, which remained elevated for 48 h post-irradiation (which was the latest time assayed in these studies). Mixing studies revealed that Factor IX contributed to the increased aPTT values. A majority of the animals exposed at the LDR had an International Normalized Ratio approaching or surpassing 2.0. Conclusions PT/aPTT assays resulted in increased clotting times due to different coagulation factors, indicating potential radiation-induced coagulopathy. PMID:22221163

Amlodipine at high dose increases preproendothelin-1 expression in the ventricles and aorta of normotensive rats.

PubMed

Krenek, Peter; Morel, Nicole; Kyselovic, Jan; Wibo, Maurice

2004-04-01

High doses of dihydropyridine calcium channel blockers can activate the sympathetic nervous system and the renin-angiotensin system. Both noradrenaline and angiotensin II stimulate preproendothelin-1 gene expression, yet the effects of high doses of dihydropyridines on preproendothelin-1 expression in vivo remain unknown. To investigate the effects of high doses of dihydropyridines on preproendothelin-1 expression in the ventricles and aorta of normotensive rats. Sprague-Dawley rats were treated with amlodipine 5 or 20 mg/kg per day (Amlo 5 or Amlo 20) in drinking water for 5 days or 5 weeks. Systolic blood pressure and heart rate were measured by tail-cuff plethysmography. Gene expression was examined by reverse transcriptase polymerase chain reaction. Amlo 5 increased heart rate during the first week only and had no effect on blood pressure and ventricular weight and gene expression. Amlo 20 reduced blood pressure transiently and increased heart rate consistently. It did not change relative left ventricular weight (corrected for body weight) after 5 days, but increased it after 5 weeks; it increased relative right ventricular weight at both time points. Aorta weight (mg/mm) was decreased after 5 weeks of treatment with both dosages of amlodipine. Preproendothelin-1 mRNA levels were increased by Amlo 20 in the ventricles and aorta and, concomitantly, renin mRNA was increased in the kidney. Less consistently, interleukin-6 mRNA also increased in ventricles, whereas cardiotrophin-1 mRNA remained unchanged. The sensitivity of isolated aorta to the contractile effect of noradrenaline was decreased by Amlo 5, but not by Amlo 20. In Sprague-Dawley rats, high-dose amlodipine, while promoting neurohormonal activation, induced overexpression of preproendothelin-1 mRNA in the ventricles and aorta. Endothelin-1 overexpression could contribute to the lack of inhibitory effect of high-dose amlodipine on ventricular mass in normotensive rats.

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.

Characterisation of MR reactor pond in nNRC 'Kurchatov institute' before dismantling work

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

Stepanov, Alexey; Simirsky, Yury; Semin, Ilya

2013-07-01

In this work complex α-, β-, γ-spectrometric research of water, bottom slimes and deposits on walls of the reactor pond and the storage pond of the MR reactor was made. Identify, that the main dose forming radionuclide, during dismantling work on the reactor MR, is Cs-137. It is shown, that specific activity of radionuclides in bottom slimes considerably exceed specific activity of radionuclides in water from ponds, and near to high level radioactive waste. It is detected that decreasing the water level in reactor ponds on 1 m, increase the exposure dose rate at a distance 1 m from themore » pond in 2 times. The observed increase in exposure dose rate can be explained by contribution on dose rate the cesium-137 deposed on walls of the storage pond. Effectiveness of cleaning of walls of the pool of storage from deposits by a water jet of high pressure is investigated. (authors)« less

Using rainfall radar data to improve interpolated maps of dose rate in the Netherlands.

PubMed

Hiemstra, Paul H; Pebesma, Edzer J; Heuvelink, Gerard B M; Twenhöfel, Chris J W

2010-12-01

The radiation monitoring network in the Netherlands is designed to detect and track increased radiation levels, dose rate more specifically, in 10-minute intervals. The network consists of 153 monitoring stations. Washout of radon progeny by rainfall is the most important cause of natural variations in dose rate. The increase in dose rate at a given time is a function of the amount of progeny decaying, which in turn is a balance between deposition of progeny by rainfall and radioactive decay. The increase in progeny is closely related to average rainfall intensity over the last 2.5h. We included decay of progeny by using weighted averaged rainfall intensity, where the weight decreases back in time. The decrease in weight is related to the half-life of radon progeny. In this paper we show for a rainstorm on the 20th of July 2007 that weighted averaged rainfall intensity estimated from rainfall radar images, collected every 5min, performs much better as a predictor of increases in dose rate than using the non-averaged rainfall intensity. In addition, we show through cross-validation that including weighted averaged rainfall intensity in an interpolated map using universal kriging (UK) does not necessarily lead to a more accurate map. This might be attributed to the high density of monitoring stations in comparison to the spatial extent of a typical rain event. Reducing the network density improved the accuracy of the map when universal kriging was used instead of ordinary kriging (no trend). Consequently, in a less dense network the positive influence of including a trend is likely to increase. Furthermore, we suspect that UK better reproduces the sharp boundaries present in rainfall maps, but that the lack of short-distance monitoring station pairs prevents cross-validation from revealing this effect. Copyright © 2010 Elsevier B.V. All rights reserved.

A quality improvement initiative to increase HPV vaccine rates using an educational and reminder strategy with parents of preteen girls.

PubMed

Cassidy, Brenda; Braxter, Betty; Charron-Prochownik, Denise; Schlenk, Elizabeth A

2014-01-01

A quality improvement project was undertaken to determine if an evidence-based educational brochure and reminder system can increase human papillomavirus (HPV) vaccine uptake and dose completion rates. Development of a brochure to promote HPV vaccine uptake was based on predictors of parental acceptance and Health Belief Model concepts. Electronic alerts prompted telephone reminders for dose completion. This quality improvement project utilized a quasi-experimental design with 24 parents of preteen girls from a private pediatric practice and a historical control group of 29 parents. HPV vaccine rates were compared between the groups. A significant difference in HPV vaccine uptake (χ(2) = 11.668, P = .001; odds ratio [OR] = 9.429, 95% confidence interval [CI] = 2.686-33.101) and dose completion (χ(2) = 16.171, P < .001; OR = 22.500, 95% CI = 4.291-117.990) rates were found between the historical control and intervention groups. Parents who received the clinical protocol were 9.4 times and 22.5 times more likely to have HPV vaccine uptake and dose completion, respectively. Low national HPV vaccine rates demonstrate the need for theory-based vaccine delivery programs. These results show that an evidence-based educational brochure and reminder system appeared to improve HPV vaccine uptake and dose completion rates at this private pediatric practice. Copyright © 2014 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

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

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi

2012-09-15

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase weremore » extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.« less

β-blocker dosage and outcomes after acute coronary syndrome.

PubMed

Allen, Jason E; Knight, Stacey; McCubrey, Raymond O; Bair, Tami; Muhlestein, Joseph Brent; Goldberger, Jeffrey J; Anderson, Jeffrey L

2017-02-01

Although β-blockers increase survival in acute coronary syndrome (ACS) patients, the doses used in trials were higher than doses used in practice, and recent data do not support an advantage of higher doses. We hypothesized that rates of major adverse cardiac events (MACE), all-cause death, myocardial infarction, and stroke are equivalent for patients on low-dose and high-dose β-blocker. Patients admitted to Intermountain Healthcare with ACS and diagnosed with ≥70% coronary stenosis between 1994 and 2013 were studied (N = 7,834). We classified low dose as ≤25% and high dose as ≥50% of an equivalent daily dose of 200 mg of metoprolol. Multivariate analyses were used to test association between low-dose versus high-dose β-blocker dosage and MACE at 0-6 months and 6-24 months. A total of 5,287 ACS subjects were discharged on β-blockers (87% low dose, 12% high dose, and 1% intermediate dose). The 6-month MACE outcomes rates for the β-blocker dosage (low versus high) were not equivalent (P = .18) (hazard ratio [HR] = 0.76; 95% CI, 0.52-1.10). However, subjects on low-dose β-blocker therapy did have a significantly decreased risk of myocardial infarction for 0-6 months (HR = 0.53; 95% CI, 0.33-0.86). The rates of MACE events during the 6-24 months after presentation with ACS were equivalent for the 2 doses (P = .009; HR = 1.03 [95% CI, 0.70-1.50]). In ACS patients, rates of MACE for high-dose and low-dose β-blocker doses are similar. These findings question the importance of achieving a high dose of β-blocker in ACS patients and highlight the need for further investigation of this clinical question. Copyright © 2016 Elsevier Inc. All rights reserved.

Technical Note: On maximizing Cherenkov emissions from medical linear accelerators.

PubMed

Shrock, Zachary; Yoon, Suk W; Gunasingha, Rathnayaka; Oldham, Mark; Adamson, Justus

2018-04-19

Cherenkov light during MV radiotherapy has recently found imaging and therapeutic applications but is challenged by relatively low fluence. Our purpose is to investigate the feasibility of increasing Cherenkov light production during MV radiotherapy by increasing photon energy and applying specialized beam-hardening filtration. GAMOS 5.0.0, a GEANT4-based framework for Monte Carlo simulations, was used to model standard clinical linear accelerator primary photon beams. The photon source was incident upon a 17.8 cm 3 cubic water phantom with a 94 cm source to surface distance. Dose and Cherenkov production was determined at depths of 3-9 cm. Filtration was simulated 15 cm below the photon beam source. Filter materials included aluminum, iron, and copper with thicknesses of 2-20 cm. Histories used depended on the level of attenuation from the filter, ranging from 100 million to 2 billion. Comparing average dose per history also allowed for evaluation of dose-rate reduction for different filters. Overall, increasing photon beam energy is more effective at improving Cherenkov production per unit dose than is filtration, with a standard 18 MV beam yielding 3.3-4.0× more photons than 6 MV. Introducing an aluminum filter into an unfiltered 2400 cGy/min 10 MV beam increases the Cherenkov production by 1.6-1.7×, while maintaining a clinical dose rate of 300 cGy/min, compared to increases of ~1.5× for iron and copper. Aluminum was also more effective than the standard flattening filter, with the increase over the unfiltered beam being 1.4-1.5× (maintaining 600 cGy/min dose rate) vs 1.3-1.4× for the standard flattening filter. Applying a 10 cm aluminum filter to a standard 18 MV, photon beam increased the Cherenkov production per unit dose to 3.9-4.3× beyond that of 6 MV (vs 3.3-4.0× for 18 MV with no aluminum filter). Through a combination of increasing photon energy and applying specialized beam-hardening filtration, the amount of Cherenkov photons per unit radiotherapy dose can be increased substantially. © 2018 American Association of Physicists in Medicine.

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning.

PubMed

Abugideiri, Mustafa; Nanda, Ronica H; Butker, Charlotte; Zhang, Chao; Kim, Sungjin; Chiang, Kuang-Yueh; Butker, Elizabeth; Khan, Mohammad K; Haight, Ann E; Chen, Zhengjia; Esiashvili, Natia

2016-02-01

This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS. Copyright © 2016 Elsevier Inc. All rights reserved.

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning

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

Abugideiri, Mustafa, E-mail: Mabugid@emory.edu; Nanda, Ronica H.; Butker, Charlotte

Purpose: This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). Methods and Materials: The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified usingmore » clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. Results: PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. Conclusions: A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS.« less

Experimental study of radiation dose rate at different strategic points of the BAEC TRIGA Research Reactor.

PubMed

Ajijul Hoq, M; Malek Soner, M A; Salam, M A; Haque, M M; Khanom, Salma; Fahad, S M

2017-12-01

The 3MW TRIGA Mark-II Research Reactor of Bangladesh Atomic Energy Commission (BAEC) has been under operation for about thirty years since its commissioning at 1986. In accordance with the demand of fundamental nuclear research works, the reactor has to operate at different power levels by utilizing a number of experimental facilities. Regarding the enquiry for safety of reactor operating personnel and radiation workers, it is necessary to know the radiation level at different strategic points of the reactor where they are often worked. In the present study, neutron, beta and gamma radiation dose rate at different strategic points of the reactor facility with reactor power level of 2.4MW was measured to estimate the rising level of radiation due to its operational activities. From the obtained results high radiation dose is observed at the measurement position of the piercing beam port which is caused by neutron leakage and accordingly, dose rate at the stated position with different reactor power levels was measured. This study also deals with the gamma dose rate measurements at a fixed position of the reactor pool top surface for different reactor power levels under both Natural Convection Cooling Mode (NCCM) and Forced Convection Cooling Mode (FCCM). Results show that, radiation dose rate is higher for NCCM in compared with FCCM and increasing with the increase of reactor power. Thus, concerning the radiological safety issues for working personnel and the general public, the radiation dose level monitoring and the experimental analysis performed within this paper is so much effective and the result of this work can be utilized for base line data and code verification of the nuclear reactor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of proton beam irradiation on seed germination and growth of soybean ( Glycine max L. Merr.)

NASA Astrophysics Data System (ADS)

Im, Juhyun; Kim, Woon Ji; Kim, Sang Hun; Ha, Bo-Keun

2017-12-01

The present study aimed to evaluate the morphological effects of proton beam irradiation on the seed germination, seedling survival, and plant growth of soybean. Seeds of three Korean elite cultivars (Kwangankong, Daepungkong, and Pungsannamulkong) were irradiated with a 57-MeV proton beam in the range of 50 - 400 Gy. The germination rates of all the varieties increased to > 95%; however, the survival rates were significantly reduced. At doses of > 300 Gy irradiation, the Daepungkong, Kwangankong, and Pungsannamulkong cultivars exhibited 39, 75, and 71% survival rates, respectively. In addition, plant height and the fresh weight of shoots and roots were significantly decreased by doses of > 100 Gy irradiation, as were the dry weights of the shoots and roots. However, SPAD values increased with increasing doses of irradiation. Abnormal plants with atypically branched stems, modified leaves, and chlorophyll mutations were observed. Based on the survival rate, plant growth inhibition, and mutation frequency, it appears that the optimum dosage of proton beam irradiation for soybean mutation breeding is between 250 and 300 Gy.

Effect of radiocesium transfer on ambient dose rate in forest environments affected by the Fukushima Nuclear Power Plant accident

NASA Astrophysics Data System (ADS)

Kato, H.

2015-12-01

We investigated the transfer of canopy-intercepted radiocesium to the forest floor during 3 years following the Fukushima Daiichi Nuclear Power Plant accident. The cesium-137 (Cs-137) contents in throughfall, stemflow, and litterfall were monitored in two coniferous stands (plantation of Japanese cedar) and a deciduous broad-leaved forest stand (Japanese oak with red pine). We also measured the ambient dose rate (ADR) at different heights in the forest using a survey meter and a portable Ge gamma-ray detector. Total Cs-137 deposition flux from the canopy to forest floor for the mature cedar, young cedar, and the mixed broad-leaved stands were 166 kBq/m2, 174 kBq/m2, and 60 kBq/m2, respectively. These values correspond to 38%, 40% and 13% of total atmospheric input after the accident. The ambient dose rate in forest exhibited height dependency and its vertical distribution varied with forest type and stand age. The ambient dose rate showed an exponential decrease with time for all the forest sites, however the decreasing trend differed depending on the height of dose measurement and forest type. The ambient dose rate at the canopy (approx. 10 m-height) decreased faster than that expected from physical decay of the two radiocesium isotopes, whereas those at the forest floor varied between the three forest stands. The radiocesium deposition via throughfall seemed to increase ambient dose rate during the first 200 days after the accident, however there was no clear relationship between litterfall and ambient dose rate since 400 days after the accident. These data suggested that the ambient dose rate in forest environment varied both spatially and temporally reflecting the transfer of radiocesium from canopy to forest floor. However, further monitoring investigation and analysis are required to determine the effect of litterfall on long-term trend of ambient dose rate in forest environments.

Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

PubMed

Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Waite, Susan; Loo, Colleen K

2017-12-01

Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.

Thromboelastogram-guided enoxaparin dosing does not confer protection from deep venous thrombosis: a randomized controlled pilot trial.

PubMed

Louis, Scott G; Van, Philbert Y; Riha, Gordon M; Barton, Jeffrey S; Kunio, Nicholas R; Underwood, Samantha J; Differding, Jerome A; Rick, Elizabeth; Ginzburg, Enrique; Schreiber, Martin A

2014-04-01

The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates. A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations. A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency. TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway. Therapeutic study, level III.

SU-F-T-236: Comparison of Two IMRT/VMAT QA Systems Using Gamma Index Analysis

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

Dogan, N; Denissova, S

2016-06-15

Purpose: The goal of this study is to assess differences in the Gamma index pass rates when using two commercial QA systems and provide optimum Gamma index parameters for pre-treatment patient specific QA. Methods: Twenty-two VMAT cases that consisted of prostate, lung, head and neck, spine, brain and pancreas, were included in this study. The verification plans have been calculated using AcurosXB(V11) algorithm for different dose grids (1.5mm, 2.5mm, 3mm). The measurements were performed on TrueBeam(Varian) accelerator using both EPID(S1000) portal imager and ArcCheck(SunNuclearCorp) devices. Gamma index criteria variation of 3%/3mm, 2%/3mm, 2%/2mm and threshold (TH) doses of 5% tomore » 50% were used in analysis. Results: The differences in Gamma pass rates between two devices are not statistically significant for 3%/3mm, yielding pass rate higher than 95%. Increase of lower dose TH showed reduced pass rates for both devices. ArcCheck’s more pronounced effect can be attributed to higher contribution of lower dose region spread. As expected, tightening criteria to 2%/2mm (TH: 10%) decreased Gamma pass rates below 95%. Higher EPID (92%) pass rates compared to ArcCheck (86%) probably due to better spatial resolution. Portal Dosimetry results showed lower Gamma pass rates for composite plans compared to individual field pass rates. This may be due to the expansion in the analyzed region which includes pixels not included in the separate field analysis. Decreasing dose grid size from 2.5mm to 1.5mm did not show statistically significant (p<0.05) differences in Gamma pass rates for both QA devices. Conclusion: Overall, both system measurements agree well with calculated dose when using gamma index criteria of 3%/3mm for a variety of VMAT cases. Variability between two systems increases using different dose GRID, TH and tighter gamma criteria and must be carefully assessed prior to clinical use.« less

Cocaine self-administration under variable-dose schedules in squirrel monkeys.

PubMed

Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W

2006-06-01

Squirrel monkeys self-administered cocaine under a variable-dose schedule, with the dose varied from injection to injection. As in earlier studies with rats, post-injection pauses varied as a monotonic function of dose, allowing a cocaine dose-effect curve to be obtained during each session. These curves were shifted by pretreatment with dopamine antagonists, demonstrating that this procedure may provide an efficient means of evaluating treatments that affect drug self-administration. However, drug intake eventually became "dysregulated" after extensive training (100-300 sessions), with relatively short pauses following all doses. Dose-sensitivity was restored by adding a 60-s timeout period after each injection, suggesting that dysregulation occurred because the monkeys developed a tendency to self-administer another injection before the previous injection had been adequately distributed. Finally, when the response requirement under the variable-dose schedule was increased from 1 to 10, both the post-injection pause and the rate of responding following the pause ("run rates") were found to vary with dose. The dose-dependency of run rates suggests that post-injection pauses reflect not only motivational factors, such as satiety, but also the direct effects of cocaine on leverpressing.

Environmental dose rate distribution along the Romanian Black Sea shore

NASA Astrophysics Data System (ADS)

Duliu, Octavian G.; Margineanu, Romul M.; Blebea-Apostu, Ana-Maria; Gomoiu, Claudia; Bercea, Sorin

2013-04-01

The radiometric investigation of the natural radioactivity dose rate distribution along the most important Romanian Black Sea tourist resorts showed values between 34 and 54 nSv/h, lower than the 59 nSv/h, the average background reported for the entire Romanian territory. At the same time we have noticed that the experimental dose rates monotonously increase northward, reaching a maximum in the vicinity of Vadu and Corbu beaches, both on the southern part of the Chituc sandbank. Concurrent gamma ray spectrometric measurements, performed at the Slanic-Prahova Low-Background Radiation Laboratory for sand samples collected from the same location, have shown that the natural radionuclides have a major contribution to background radiation while anthropogenic Cs-137 plays, 26 years after Chernobyl catastrophe, a negligible role. The experimental values of activity concentrations of all radionuclides present in sand samples were used to calculate the corresponding values of dose rates to which, by adding the contribution of cosmic rays, we have obtained values coincident, within experimental uncertainties, with the experimental ones. At the same time, on Chituc sandbank, a transverse profile of dose rate distribution revealed the presence of some local maxima, two to thee times higher then the average ones. Subsequent gamma ray spectrometry showed an increased content of natural radionuclides, most probably due to a local accumulation of heavy minerals, a common occurrence in the vicinity of river deltas, in our case the Danube Delta. In such a way, the monitoring of local dose rate distribution could be very useful not only in attesting the environmental quality of various resorts and beaches, but also, in signaling the presence of heavy minerals, with beneficent economic consequences.

High-dose MVCT image guidance for stereotactic body radiation therapy

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

Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.

Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machinemore » by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a clinical tomotherapy machine by increasing the LINAC pulse rate. Increasing the imaging dose results in increased CNRs; making it easier to distinguish the boundaries of low contrast objects. The imaging dose levels observed in this work are considered acceptable at our institution for SBRT treatments delivered in 3-5 fractions.« less

High-dose MVCT image guidance for stereotactic body radiation therapy.

PubMed

Westerly, David C; Schefter, Tracey E; Kavanagh, Brian D; Chao, Edward; Lucas, Dan; Flynn, Ryan T; Miften, Moyed

2012-08-01

Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp∕mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. High-dose imaging modes are made possible on a clinical tomotherapy machine by increasing the LINAC pulse rate. Increasing the imaging dose results in increased CNRs; making it easier to distinguish the boundaries of low contrast objects. The imaging dose levels observed in this work are considered acceptable at our institution for SBRT treatments delivered in 3-5 fractions.

Atomoxetine Increased Effect over Time in Adults with Attention-Deficit/Hyperactivity Disorder Treated for up to 6 Months: Pooled Analysis of Two Double-Blind, Placebo-Controlled, Randomized Trials.

PubMed

Wietecha, Linda A; Clemow, David B; Buchanan, Andrew S; Young, Joel L; Sarkis, Elias H; Findling, Robert L

2016-07-01

Changes in the magnitude of efficacy throughout 26 weeks of atomoxetine treatment, along with impact of dosing, were evaluated in adults with ADHD from two randomized, double-blind, placebo-controlled studies. Pooled placebo (n = 485) and atomoxetine (n = 518) patients, dosed 25, 40, 60, 80 (target dose), or 100 mg daily, were assessed. Change from baseline in Conners' Adult ADHD Rating Scale-Investigator Rated Scale: Screening Version (CAARS) total ADHD symptoms score and Adult ADHD Investigator Symptom Rating Scale (AISRS) total score were analyzed using mixed-model repeated measures, with least squares mean change, effect size, and response rate calculated at 1, 2, 4, 8, 12, 16, 22, and 26 weeks. Decreases on CAARS for atomoxetine- versus placebo-treated patients were consistently statistically significantly greater at every time point beginning at one week (P ≤ 0.006, 0.28 effect size). By 4 weeks, comparison was -13.19 compared with -8.84 (P < 0.0001, 0.45 effect size). By 26 weeks, mean change was -15.42 versus -9.71 (0.52 effect size); increase in effect size over time was most pronounced in the 80 mg group (0.82 effect size). AISRS demonstrated similar results. Atomoxetine response rate (CAARS 50% decrease) continued to increase throughout 26 weeks. Atomoxetine treatment in adults with ADHD was associated with small effect sizes after 4 weeks and moderate effect sizes by 6 months of treatment. The data support increased effect size and response rate over time during longer-term treatment at target dose. © 2016 Eli Lilly and Company. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Degradation and annealing studies on gamma rays irradiated COTS PPD CISs at different dose rates

NASA Astrophysics Data System (ADS)

Wang, Zujun; Ma, Yingwu; Liu, Jing; Xue, Yuan; He, Baoping; Yao, Zhibin; Huang, Shaoyan; Liu, Minbo; Sheng, Jiangkun

2016-06-01

The degradation and annealing studies on Colbalt-60 gamma-rays irradiated commercial-off-the-shelf (COTS) pinned photodiode (PPD) CMOS image sensors (CISs) at the various dose rates are presented. The irradiation experiments of COTS PPD CISs are carried out at 0.3, 3.0 and 30.0 rad(Si)/s. The COTS PPD CISs are manufactured using a standard 0.18-μm CMOS technology with four-transistor pixel PPD architecture. The behavior of the tested CISs shows a remarkable degradation after irradiation and differs in the dose rates. The dark current, dark signal non-uniformity (DSNU), random noise, saturation output, signal to noise ratio (SNR), and dynamic range (DR) versus the total ionizing dose (TID) at the various dose rates are investigated. The tendency of dark current, DSNU, and random noise increase and saturation output, SNR, and DR to decrease at 3.0 rad(Si)/s are far greater than those at 0.3 and 30.0 rad(Si)/s. The damage mechanisms caused by TID irradiation at the various dose rates are also analyzed. The annealing tests are carried out at room temperature with unbiased conditions after irradiation.

NOTE: Investigating the potential of polymer gel dosimetry for interventional radiology: first results

NASA Astrophysics Data System (ADS)

Antoniou, P. E.; Bousbouras, P.; Sandaltzopoulos, R.; Kaldoudi, E.

2008-04-01

Complex interventional radiology (IR) procedures contribute an increasing percentage of the overall medical radiation exposure of the population making accurate dosimetry a challenge. Magnetic resonance (MR) based polymer gel dosimetry has been widely employed in complex dosimetric problems in radiotherapy. The aim of this note is to investigate the feasibility of normoxic gel dosimetry in IR. Dose response, energy dependence and dose rate dependence were investigated in irradiation set-ups relevant to IR for a particular normoxic gel, based on methacrylic acid (MAA) as the monomer and including tetrakis-hydroxy-methyl-phosphonium chloride (THPC) as antioxidant. The gel presents a linear dose response beyond a 25 cGy threshold. No significant energy dependence was observed in the useful range of interventional radiology (80-110 kVp). A linear correlation between the gel response and dose rate was observed in the range of dose rates relevant to IR (5-8 cGy min-1). These results demonstrate a reduction of gel sensitivity at very low dose rate levels. A possible explanation of this effect is suggested.

Caffeine induces a second wave of apoptosis after low dose-rate gamma radiation of HL-60 cells.

PubMed

Vávrová, Jirina; Mareková-Rezácová, Martina; Vokurková, Doris; Szkanderová, Sylva; Psutka, Jan

2003-10-01

Most cell lines that lack functional p53 protein are arrested in the G(2) phase of the cell cycle due to DNA damage. It was previously found that the human promyelocyte leukemia cells HL-60 (TP53 negative) that had been exposed to ionizing radiation at doses up to 10 Gy were arrested in the G(2) phase for a period of 24 h. The radioresistance of HL-60 cells that were exposed to low dose-rate gamma irradiation of 3.9 mGy/min, which resulted in a pronounced accumulation of the cells in the G(2) phase during the exposure period, increased compared with the radioresistance of cells that were exposed to a high dose-rate gamma irradiation of 0.6 Gy/min. The D(0) value (i.e. the radiation dose leading to 37% cell survival) for low dose-rate radiation was 3.7 Gy and for high dose-rate radiation 2.2 Gy. In this study, prevention of G(2) phase arrest by caffeine (2 mM) and irradiation of cells with low dose-rate irradiation in all phases of the cell cycle proved to cause radiosensitization (D(0)=2.2 Gy). The irradiation in the presence of caffeine resulted in a second wave of apoptosis on days 5-7 post-irradiation. Caffeine-induced apoptosis occurring later than day 7 post-irradiation is postulated to be a result of unscheduled DNA replication and cell cycle progress.

Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum.

PubMed

Johnson, Matthew W; MacLean, Katherine A; Reissig, Chad J; Prisinzano, Thomas E; Griffiths, Roland R

2011-05-01

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2(A)) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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.

The Effect of Measurement Area on Modelling UVR Dose to the Inner Canthus

NASA Astrophysics Data System (ADS)

Birt, Benjamin; Cowling, Ian; Coyne, Steve

People are exposed to varying amounts of UVR throughout their life from both natural and artificial light sources. The dose and rate of UVR exposure required for the formation of non-melanoma skin cancers is inconclusive. Certain regions on the face appear to exhibit a high rate of occurrence of Basal Cell Carcinomas (BCCs) in relation to the perceived dose of UVR. One of these regions is the inner canthus located on the medial side of the eye. The inner canthus appears to be well protected from large direct doses of ultraviolet radiation (UVR). Facial features such as eyelids, eye brow ridge, nasal bridge and cheek, combine to limit the solid angle of the field of view of the inner canthus to UVR from overhead sources. To explain the unexpected high rate of BCCs it is hypothesized that a percentage of the radiation incident on the eye is reflected onto the inner canthus. This paper showed that a portion of the radiation incident onto the eye was reflected towards the inner canthus. The percentage increase above the direct dose was only 2% across the whole region. As the detector elements decrease in size it is observed on a cellular level that some of the cells dose increased by 30% when the reflections were considered.

Dose-Rate Effects in Breaking DNA Strands by Short Pulses of Extreme Ultraviolet Radiation.

PubMed

Vyšín, Luděk; Burian, Tomáš; Ukraintsev, Egor; Davídková, Marie; Grisham, Michael E; Heinbuch, Scott; Rocca, Jorge J; Juha, Libor

2018-05-01

In this study, we examined dose-rate effects on strand break formation in plasmid DNA induced by pulsed extreme ultraviolet (XUV) radiation. Dose delivered to the target molecule was controlled by attenuating the incident photon flux using aluminum filters as well as by changing the DNA/buffer-salt ratio in the irradiated sample. Irradiated samples were examined using agarose gel electrophoresis. Yields of single- and double-strand breaks (SSBs and DSBs) were determined as a function of the incident photon fluence. In addition, electrophoresis also revealed DNA cross-linking. Damaged DNA was inspected by means of atomic force microscopy (AFM). Both SSB and DSB yields decreased with dose rate increase. Quantum yields of SSBs at the highest photon fluence were comparable to yields of DSBs found after synchrotron irradiation. The average SSB/DSB ratio decreased only slightly at elevated dose rates. In conclusion, complex and/or clustered damages other than cross-links do not appear to be induced under the radiation conditions applied in this study.

Dose rate calculations around 192Ir brachytherapy sources using a Sievert integration model

NASA Astrophysics Data System (ADS)

Karaiskos, P.; Angelopoulos, A.; Baras, P.; Rozaki-Mavrouli, H.; Sandilos, P.; Vlachos, L.; Sakelliou, L.

2000-02-01

The classical Sievert integral method is a valuable tool for dose rate calculations around brachytherapy sources, combining simplicity with reasonable computational times. However, its accuracy in predicting dose rate anisotropy around 192 Ir brachytherapy sources has been repeatedly put into question. In this work, we used a primary and scatter separation technique to improve an existing modification of the Sievert integral (Williamson's isotropic scatter model) that determines dose rate anisotropy around commercially available 192 Ir brachytherapy sources. The proposed Sievert formalism provides increased accuracy while maintaining the simplicity and computational time efficiency of the Sievert integral method. To describe transmission within the materials encountered, the formalism makes use of narrow beam attenuation coefficients which can be directly and easily calculated from the initially emitted 192 Ir spectrum. The other numerical parameters required for its implementation, once calculated with the aid of our home-made Monte Carlo simulation code, can be used for any 192 Ir source design. Calculations of dose rate and anisotropy functions with the proposed Sievert expression, around commonly used 192 Ir high dose rate sources and other 192 Ir elongated source designs, are in good agreement with corresponding accurate Monte Carlo results which have been reported by our group and other authors.

Radiation Pneumopathy in the Rat After Intravenous Application of {sup 188}Re-Labeled Microspheres

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

Liepe, Knut; Faulhaber, Diana; Wunderlich, Gerd

2011-10-01

Purpose: To determine the dose dependence and kinetics of pneumopathy after systemic administration of rhenium-188 ({sup 188}Re)-labeled microspheres in a rat model. Methods and Materials: {sup 188}Re-microspheres were injected intravenously into adult Wistar rats (n = 54, age, 8 {+-} 2 months). The rats were divided into 6 groups according to the intended absorbed dose in the lung (maximum 60 Gy). Gamma camera scans were used to estimate the individual whole lung doses. One control group (n = 5) received nonlabeled microspheres. The breathing rate was measured before and weekly after the treatment using whole body plethysmography until 24 weeks.more » An increase in the breathing rate by 20% compared with the individual pretreatment control value was defined as the quantal endpoint for dose-effect analyses. Results: A biphasic increase in the breathing rate was observed. The first impairment of lung function occurred in Weeks 3-6. For late changes, the interval to onset was clearly dose dependent and was 17 weeks (10-30 Gy) and 10 weeks (50-60 Gy), respectively. The incidence of the response was highly dependent on the estimated lung dose. The median effective dose for an early and late response was virtually identical (19.9 {+-} 0.6 Gy and 20.4 {+-} 3.1 Gy, respectively). A significant correlation was found between the occurrence of an early and a late effect in the same rat, suggesting a strong consequential component. Conclusions: The effects of radiolabeled microspheres can be studied longitudinally in a rat model, using changes in the breathing rate as the functional, clinically relevant response. The isoeffective doses from the present study using radionuclide administration and those from published investigations of homogeneous external beam radiotherapy are almost similar.« less

Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial

PubMed Central

McAfee, Tim; Davis, Kevin C; Shafer, Paul; Patel, Deesha; Alexander, Robert; Bunnell, Rebecca

2017-01-01

Background While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose–response from the campaign was only assessed by self-report. Objective Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. Methods A 3-month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. Results In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard-dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. Conclusions The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non-smokers and further increasing quit attempts among smokers, especially African-Americans. PMID:26678518

Measuring in vitro biotransformation rates of super hydrophobic chemicals in rat liver s9 fractions using thin-film sorbent-phase dosing.

PubMed

Lee, Yung-Shan; Otton, S Victoria; Campbell, David A; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2012-01-03

Methods for rapid and cost-effective assessment of the biotransformation potential of very hydrophobic and potentially bioaccumulative chemicals in mammals are urgently needed for the ongoing global evaluation of the environmental behavior of commercial chemicals. We developed and tested a novel solvent-free, thin-film sorbent-phase in vitro dosing system to measure the in vitro biotransformation rates of very hydrophobic chemicals in male Sprague-Dawley rat liver S9 homogenates and compared the rates to those measured by conventional solvent-delivery dosing. The thin-film sorbent-phase dosing system using ethylene vinyl acetate coated vials was developed to eliminate the incomplete dissolution of very hydrophobic substances in largely aqueous liver homogenates, to determine biotransformation rates at low substrate concentrations, to measure the unbound fraction of substrate in solution, and to simplify chemical analysis by avoiding the difficult extraction of test chemicals from complex biological matrices. Biotransformation rates using sorbent-phase dosing were 2-fold greater than those measured using solvent-delivery dosing. Unbound concentrations of very hydrophobic test chemicals were found to decline with increasing S9 and protein concentrations, causing measured biotransformation rates to be independent of S9 or protein concentrations. The results emphasize the importance of specifying both protein content and unbound substrate fraction in the measurement and reporting of in vitro biotransformation rates of very hydrophobic substances, which can be achieved in a thin-film sorbent-phase dosing system.

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.

Room model based Monte Carlo simulation study of the relationship between the airborne dose rate and the surface-deposited radon progeny.

PubMed

Sun, Kainan; Field, R William; Steck, Daniel J

2010-01-01

The quantitative relationships between radon gas concentration, the surface-deposited activities of various radon progeny, the airborne radon progeny dose rate, and various residential environmental factors were investigated through a Monte Carlo simulation study based on the extended Jacobi room model. Airborne dose rates were calculated from the unattached and attached potential alpha-energy concentrations (PAECs) using two dosimetric models. Surface-deposited (218)Po and (214)Po were significantly correlated with radon concentration, PAECs, and airborne dose rate (p-values <0.0001) in both non-smoking and smoking environments. However, in non-smoking environments, the deposited radon progeny were not highly correlated to the attached PAEC. In multiple linear regression analysis, natural logarithm transformation was performed for airborne dose rate as a dependent variable, as well as for radon and deposited (218)Po and (214)Po as predictors. In non-smoking environments, after adjusting for the effect of radon, deposited (214)Po was a significant positive predictor for one dose model (RR 1.46, 95% CI 1.27-1.67), while deposited (218)Po was a negative predictor for the other dose model (RR 0.90, 95% CI 0.83-0.98). In smoking environments, after adjusting for radon and room size, deposited (218)Po was a significant positive predictor for one dose model (RR 1.10, 95% CI 1.02-1.19), while a significant negative predictor for the other model (RR 0.90, 95% CI 0.85-0.95). After adjusting for radon and deposited (218)Po, significant increases of 1.14 (95% CI 1.03-1.27) and 1.13 (95% CI 1.05-1.22) in the mean dose rates were found for large room sizes relative to small room sizes in the different dose models.

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

PubMed

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René; Chrystyn, Henry

2015-10-01

Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

Microfluidic Thrombosis under Multiple Shear Rates and Antiplatelet Therapy Doses

PubMed Central

Ku, David N.; Forest, Craig R.

2014-01-01

The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s−1) and therapy concentrations (0–2.4 µM for eptifibatide, 0–2 mM for acetyl-salicylic acid (ASA), 3.5–40 Units/L for heparin) using a microfluidic device. We also measured complete blood counts (CBC) and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose). Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment. PMID:24404131

Clinical outcomes and cost minimization with an alternative dosing regimen for meropenem in a community hospital.

PubMed

Patel, Gita Wasan; Duquaine, Susan M; McKinnon, Peggy S

2007-12-01

To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. Retrospective cohort study with a cost-minimization analysis. A 417-bed, privately owned community hospital. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

DTIC Science & Technology

2007-02-01

bladder and the rectum are overprotected while the PTV coverage is undesirably reduced. On the other hand, if their maximum dose is increased and/or...B, the bladder and rectum were overprotected with undesirably low PTV coverage (84.54%). The reduction of their weighting factor increased PTV

Multi-scale simulation of radiation damage accumulation and subsequent hardening in neutron-irradiated α-Fe

DOE PAGES

Dunn, Aaron; Dingreville, Remi; Capolungo, Laurent

2015-11-27

A hierarchical methodology is introduced to predict the effects of radiation damage and irradiation conditions on the yield stress and internal stress heterogeneity developments in polycrystalline α-Fe. Simulations of defect accumulation under displacement cascade damage conditions are performed using spatially resolved stochastic cluster dynamics. The resulting void and dislocation loop concentrations and average sizes are then input into a crystal plasticity formulation that accounts for the change in critical resolved shear stress due to the presence of radiation induced defects. The simulated polycrystalline tensile tests show a good match to experimental hardening data over a wide range of irradiation doses.more » With this capability, stress heterogeneity development and the effect of dose rate on hardening is investigated. The model predicts increased hardening at higher dose rates for low total doses. By contrast, at doses above 10 –2 dpa when cascade overlap becomes significant, the model does not predict significantly different hardening for different dose rates. In conclusion, the development of such a model enables simulation of radiation damage accumulation and associated hardening without relying on experimental data as an input under a wide range of irradiation conditions such as dose, dose rate, and temperature.« less

Acrosin activity is a suitable indicator of boar semen preservation at 17 °C when increasing environmental temperature and radiation.

PubMed

Pinart, E; Yeste, M; Puigmulé, M; Barrera, X; Bonet, S

2013-08-01

The effect of increasing environmental temperature and radiation on the sperm quality and the field fertility of refrigerated seminal doses from AI boars (N = 30) was analyzed throughout four experimental months (from March through June). In each experimental month, analyses of sperm quality were performed at days 0, 1, 3, 5, 7, and 9 of refrigeration of seminal doses; pregnancy rate and litter size were evaluated using double monospermic inseminations of multiparous female animals using seminal doses at Days 1 to 2 and Days 3 to 4 of refrigeration. Sperm quality was assessed from the evaluation of conventional parameters of sperm concentration, sperm motility, sperm morphology, and sperm viability, and capacitation parameters of membrane lipid disorder, intracellular calcium content, and acrosin activity. Results showed that sperm quality of boar seminal doses was negatively affected by increasing temperature and radiation, which resulted in significantly decreased sperm motility and viability, acrosin activity, pregnancy rate, and litter size, and significantly increased intracellular calcium levels in the trials performed in June. In any experimental month, aging of refrigerated doses was associated with the progressive increase of intracellular calcium levels and inactivation of acrosin, that began from Day 5 of storage in the trials performed in March and April, from Day 3 in those of May, and from Day 0 in those of June. Among the sperm parameters analyzed, only acrosin activity exhibited a clearly differentiated pattern in association with increasing temperature and radiation, and a significant correlation with pregnancy rate and litter size. These results highlighted the potential role of acrosin activity as an indicator of boar sperm preservation at 17 °C in boars. Copyright © 2013 Elsevier Inc. All rights reserved.

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

“Resting” CBF in the Epileptic Baboon: Correlation with Ketamine Dose and Interictal Epileptic Discharges

PubMed Central

Szabó, C. Ákos; Narayana, Shalini; Franklin, Crystal; Knape, Koyle D.; Davis, M. Duff; Fox, Peter T.; Leland, M. Michelle; Williams, Jeff T.

2011-01-01

Background Photosensitive epileptic (SZ) baboons demonstrate different cerebral blood flow (CBF) activation patterns from asymptomatic controls (CTL) during intermittent light stimulation (ILS). This study compares “resting” CBF between PS and CTL animals, and CBF correlations with ketamine dose and interictal epileptic discharges (IEDs) between PS and CTL animals. Methods Continuous intravenous ketamine was administered to eight PS and eight CTL baboons (matched for gender and weight), and maintained at subanesthetic doses (4.8–14.6 mg/kg/hr). Three resting H215O-PET studies were attempted in each animal (CTI/Siemens HR+ scanner). Images were acquired in 3D mode (63 contiguous slices, 2.4 mm thickness). PET images were co-registered with MRI images (3T Siemens Trio, T1-weighted 3D Turboflash sequence, TE/TR/TI = 3.04/2100/785 msec, flip angle=13 degrees). EEG was used to monitor depth of sedation and for quantification of IED rates. Regional CBF was compared between PS and CTL groups and correlations were analyzed for ketamine dose and IED rates. Results When subsets of animals of either group, receiving similar doses of ketamine were compared, PS animals demonstrated relative CBF increases in the occipital lobes and decreases in the frontal lobes. Correlation analyses with ketamine dose confirmed the frontal and occipital lobe changes in the PS animals. The negative correlations of CBF with ketamine dose and IED rate overlapped frontally. While frontal lobe CBF was also negatively correlated with IED rate, positive correlations were found in the parietal lobe. Conclusions “Resting” CBF differs between PS and CTL baboons. Correlation analyses of CBF and ketamine dose reveal that occipital lobe CBF increases and frontal lobe in PS animals are driven by ketamine. While frontal lobe CBF decreases may be related to ketamine’s propensity to activate IEDs, positive CBF correlations with IED rate suggest involvement of the parietal lobes in their generation. PMID:18801644

Cost comparison of unit dose and traditional drug distribution in a long-term-care facility.

PubMed

Lepinski, P W; Thielke, T S; Collins, D M; Hanson, A

1986-11-01

Unit dose and traditional drug distribution systems were compared in a 352-bed long-term-care facility by analyzing nursing time, medication-error rate, medication costs, and waste. Time spent by nurses in preparing, administering, charting, and other tasks associated with medications was measured with a stop-watch on four different nursing units during six-week periods before and after the nursing home began using unit dose drug distribution. Medication-error rate before and after implementation of the unit dose system was determined by patient profile audits and medication inventories. Medication costs consisted of patient billing costs (acquisition cost plus fee) and cost of medications destroyed. The unit dose system required a projected 1507.2 hours less nursing time per year. Mean medication-error rates were 8.53% and 0.97% for the traditional and unit dose systems, respectively. Potential annual savings because of decreased medication waste with the unit dose system were $2238.72. The net increase in cost for the unit dose system was estimated at $615.05 per year, or approximately $1.75 per patient. The unit dose system appears safer and more time-efficient than the traditional system, although its costs are higher.

Mechanical properties of carbon steel depending on the rate of the dose build-up of nitrogen and argon ions

NASA Astrophysics Data System (ADS)

Vorob'ev, V. L.; Bykov, P. V.; Bayankin, V. Ya.; Shushkov, A. A.; Vakhrushev, A. V.

2014-08-01

The effect of pulsed irradiation with argons and nitrogen ions on the mechanical properties, morphology, and structure of the surface layers of carbon steel St3 (0.2% C, 0.4% Mn, 0.15% Si, and Fe for balance) has been investigated depending on the rate of dose build-up at an average ion current density of 10, 20, and 40 μA/cm2. It has been established that the fatigue life and microhardness of surface layers increase in the entire studied range of dose build-up rates. This seems to be due to the hardening of the surface layers, which resulted from the generation of radiation defects and the irradiation-dynamic effect of fast ions. The sample irradiated by argon ions at the lowest of the selected dose build-up rates j av = 10 μA/cm2 withstands the largest number of cycles to failure.

Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

PubMed Central

Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

2018-01-01

A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR. PMID:29531508

The effects of caffeine in women during aerobic-dance bench stepping.

PubMed

Ahrens, Jennifer N; Lloyd, Lisa K; Crixell, Sylvia H; Walker, John L

2007-02-01

People of all ages and fitness levels participate regularly in aerobic-dance bench stepping (ADBS) to increase fitness and control body weight. Any reasonable method for enhancing the experience or effectiveness of ADBS would be beneficial. This study examined the acute effects of a single dose of caffeine on physiological responses during ADBS in women. When compared with a placebo, neither a 3- nor a 6-mg/kg dose of caffeine altered physiological responses or rating of perceived exertion (RPE) in 20 women (age 19-28 y) of average fitness level, not habituated to caffeine, while they performed an ADBS routine. Since neither dose of caffeine had any effect on VO2, VCO2, minute ventilation, respiratory-exchange ratio, rate of energy expenditure, heart rate, or RPE during ADBS exercise, it would not be prudent for a group exercise leader to recommend caffeine to increase energy cost or decrease perception of effort in an ADBS session. Furthermore, caffeine ingestion should not interfere with monitoring intensity using heart rate or RPE during ADBS.

EFFECTS OF REACTOR RADIATION ON THE ELECTRICAL PROPERTIES OF ELECTRONIC COMPONENTS. PART II. VACUUM TUBES, TRANSISTORS AND TRANSFORMERS

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

Miglicco, P.S.; Spears, A.B.; Howell, D.B.

1957-11-22

Several types of vacuum tubes, transistors and transformers were irradiated with the Convair-Fort Worth Ground Test Reactor. The components were subjected to five different fluxes ranging from 10/sup 6/ to 10/sup 10/n/sub F// cm/sup 2/-sec and 10/sup 8/ to 10/sup 12/ gamma /cm/sup 2/-sec. The total integrated flux received was 10/sup 14/n/sub F//cm/sup 2/ and 10/sup 16/ gamma / cm/sup 2/. An attempt was made to separate radiation damage as a function of dose rate from radiation damage as a function of dose. The components were irradiated first at several low dose rates so that dose rate effects could bemore » studied while the accumulated dose was small, and then at a high dose rate to obtain the desired dose. However, because of the long time required to complete a data gathering cycle, the accumulated dose hindered the separation of dose rate and dose effects. Thus, in the report, the damage to the components is reported as a function of integrated flux. For reference, the integrated flux accumulated at each power level is given. The transformers exhibited the greatest resistance to irradiation. Every important parameter of the transistors deteriorated in the radiation field. Postirradiation tests at room temperature showed no significant recovery in the transistor's characteristics. The plate current of 65% of the tubes tested increased during irradiation. This effect, based on postirradiation tests, is considered permanent. (auth)« less

Trivalent influenza vaccine-induced antibody response to circulating influenza a (H3N2) viruses in 2010/11 and 2011/12 seasons.

PubMed

Hiroi, Satoshi; Morikawa, Saeko; Nakata, Keiko; Maeda, Akiko; Kanno, Tsuneji; Irie, Shin; Ohfuji, Satoko; Hirota, Yoshio; Kase, Tetsuo

2015-01-01

To evaluate antibody response induced by trivalent inactivated influenza vaccine (TIV) against circulating influenza A (H3N2) strains in healthy adults during the 2010/11 and 2011/12 seasons, a hemagglutination-inhibition (HI) assay was utilized to calculate geometric mean antibody titer (GMT), seroprotection rate (post vaccination HI titers of ≥1 :40), and seroresponse rate (4-fold increase in antibody level). In the 2010/11 season, GMT increased 1.8- to 2.0-fold following the first dose of TIV against 3 circulating strains and 2.2-fold following the second compared to before vaccination. The seroresponse rate ranged from 22% to 26% following the first dose of TIV and from 31% to 33% following the second (n = 54 ). The seroprotection rate increased from a range of 6% to 13% to a range of 26% to 33% following the first dose of TIV and to a range of 37% to 42% following the second (n = 54 ). In the 2011/12 season, GMT increased 1.4-fold against A/Osaka/110/2011 and 1.8-fold against A/Osaka/5/2012. For A/Osaka/110/2011, the seroresponse rate was 29%, and the seroprotection rate increased from 26% to 55% following vaccination (n = 31 ). For A/Osaka/5/2012, the seroresponse rate was 26%, and the seroprotection rate increased from 68% to 84% following vaccination (n = 31 ). HI assays with reference antisera demonstrated that the strains in the 2011/12 season were antigenically distinct from vaccine strain (A/Victoria/210/2009). In conclusion, the vaccination increased the seroprotection rate against circulating H3N2 strains in the 2010/11 and 2011/12 seasons. Vaccination of TIV might have potential to induce reactive antibodies against antigenically distinct circulating H3N2 viruses.

Higher dose rate Gamma Knife radiosurgery may provide earlier and longer-lasting pain relief for patients with trigeminal neuralgia.

PubMed

Lee, John Y K; Sandhu, Sukhmeet; Miller, Denise; Solberg, Timothy; Dorsey, Jay F; Alonso-Basanta, Michelle

2015-10-01

Gamma Knife radiosurgery (GKRS) utilizes cobalt-60 as its radiation source, and thus dose rate varies as the fixed source decays over its half-life of approximately 5.26 years. This natural decay results in increasing treatment times when delivering the same cumulative dose. It is also possible, however, that the biological effective dose may change based on this dose rate even if the total dose is kept constant. Because patients are generally treated in a uniform manner, radiosurgery for trigeminal neuralgia (TN) represents a clinical model whereby biological efficacy can be tested. The authors hypothesized that higher dose rates would result in earlier and more complete pain relief but only if measured with a sensitive pain assessment tool. One hundred thirty-three patients were treated with the Gamma Knife Model 4C unit at a single center by a single neurosurgeon during a single cobalt life cycle from January 2006 to May 2012. All patients were treated with 80 Gy with a single 4-mm isocenter without blocking. Using an output factor of 0.87, dose rates ranged from 1.28 to 2.95 Gy/min. The Brief Pain Inventory (BPI)-Facial was administered before the procedure and at the first follow-up office visit 1 month from the procedure (mean 1.3 months). Phone calls were made to evaluate patients after their procedures as part of a retrospective study. Univariate and multivariate linear regression was performed on several independent variables, including sex, age in deciles, diagnosis, follow-up duration, prior surgery, and dose rate. In the short-term analysis (mean 1.3 months), patients' self-reported pain intensity at its worst was significantly correlated with dose rate on multivariate analysis (p = 0.028). Similarly, patients' self-reported interference with activities of daily living was closely correlated with dose rate on multivariate analysis (p = 0.067). A 1 Gy/min decrease in dose rate resulted in a 17% decrease in pain intensity at its worst and a 22% decrease in pain interference with activities of daily living. In longer-term follow-up (mean 1.9 years), GKRS with higher dose rates (> 2.0 Gy/min; p = 0.007) and older age in deciles (p = 0.012) were associated with a lower likelihood of recurrence of pain. Prior studies investigating the role of dose rate in Gamma Knife radiosurgical ablation for TN have not used validated outcome tools to measure pain preoperatively. Consequently, differences in pain outcomes have been difficult to measure. By administering pain scales both preoperatively as well as postoperatively, the authors have identified statistically significant differences in pain intensity and pain interference with activities of daily living when comparing higher versus lower dose rates. Radiosurgery with a higher dose rate results in more pain relief at the early follow-up evaluation, and it may result in a lower recurrence rate at later follow-up.

Improving the performance of membrane bioreactors by powdered activated carbon dosing with cost considerations.

PubMed

Yang, W; Paetkau, M; Cicek, N

2010-01-01

Effects of powdered activated carbon (PAC) dosing on the overall performance of membrane bioreactors (MBR) were investigated in two bench-scale submerged MBRs. Positive impacts of PAC dosing on membrane fouling and the removal of 17beta-estradiol (E2) and 17alpha-ethyinylestradiol (EE2) were demonstrated over a six-month stable operational period. PAC dosing in the MBR increased the removal rates of E2 and EE2 by 3.4% and 15.8%, respectively. The average soluble extracellular polymeric substances (EPS) and colloidal total organic carbon (TOC) concentrations in the PAC-MBR sludge was 60.1% and 61.8% lower than the control MBR sludge, respectively. Lower soluble EPS and colloidal TOC concentrations in the PAC-MBR sludge resulted in a slower rate of trans-membrane pressure (TMP) increase during MBRs operation, which could prolong the lifespan of membranes. Cost assessment showed that PAC dosing could reduce the operating cost for membrane cleaning and/or membrane replacement by about 25%. The operating cost for PAC dosing could be offset by the benefit from its reducing the cost for membrane maintenance.

Caffeine's Influence on Nicotine's Effects in Nonsmokers

PubMed Central

Blank, Melissa D.; Kleykamp, Bethea A.; Jennings, Janine M.; Eissenberg, Thomas

2011-01-01

Objective To determine if nicotine's effects are influenced by caffeine in nonsmoking, moderate-caffeine consuming individuals (N=20). Methods The first 3 sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75, or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in ascending order. The fourth session (single blind) repeated the 0 mg caffeine condition. Results Nicotine increased heart rate and subjective ratings indicative of aversive effects, and decreased reaction times. These effects were independent of caffeine dose and reliable across sessions. Conclusions In nonsmokers, nicotine effects are not influenced by moderate caffeine doses. PMID:17555378

Effects of Beta-blockers on Punished Responding and on Heart Rate in Pigeons

DTIC Science & Technology

1986-06-17

in pigeons. The present study attempted to confirm that fmding, to compare the effects of propranolol, metoprolol , and atenolol with that of...occurred at approximately 15% iii of the high unpunished response rates. Propranolol, atenolol, and metoprolol doses from 1.0 to 10.0 mg!kg, i.m. and...and, to a somewhat lesser extent, metoprolol produced large dose-related decreases. Atenolol’s effect was small. Chlordiazepoxide increased heart rate

The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin

PubMed Central

Media, Joseph; Chen, Ben; Valeriote, Fredrick

2013-01-01

Purpose UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. Materials and Methods BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg respectively on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and bodyweights were monitored. Results UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150% of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200% of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight-loss induced by cisplatin indicating that bodyweight may not be a sensitive enough measure for chemoprotection of UTL-5g against cisplatin. Conclusions In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted. PMID:23881213

The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.

PubMed

Shaw, Jiajiu; Media, Joseph; Chen, Ben; Valeriote, Fredrick

2013-09-01

UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored. UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin. In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.

Total dose radiation test methodologies for advanced spacecraft electronics experiencing enhanced low dose rate sensitivity

NASA Astrophysics Data System (ADS)

Ashton, Chris

The purpose of this thesis is to determine whether hydrogen can be implanted into elec- tronic components for the goal of investigating low ionising dose rate sensitivity, and using this to suggest whether hydrogen implantation can be used as an accelerated method to detect ELDRS (Enhanced Low Dose Rate Sensitivity) susceptability. Current ground testing methods for total ionising dose irradiate using cobalt-60 at dose rates greater than 10mGy(Si)/s up to 200Gy. It has been found that bipolar devices show an increased susceptibility to radiation induced damage at dose rates below 10mGy(Si)/s known as ELDRS. Current research has linked ELDRS susceptibility with hydrogen content within the integrated circuit and experiments based upon hydrogen soaking de-lidded bipolar devices demonstrate this relationship, however this has not led to an accepted method for testing ELDRS susceptibility in previously un-tested devices. In this thesis, a novel proposal is put forward whereby bipolar devices are directly implanted with hydrogen using a targeted ion beam in order to accelerate the testing process. Hydrogen implantation via a 600keV ion beam has been achieved to a level of 10. 17 H/cm. 2 in Analog Device’s AD590KF temperature transducer, and 10. 14-15 H/cm. 2in National Semiconductor’s LM124 quad operational amplifiers. Devices were decapped, optically analysed, and targeted with a focussed proton beam. These devices were then irradiated at 15mGy/s, 5mGy/s and 15mGy/s. Increased degradation was seen at lower dose rates which was matched by high dose rate irradiation of the implanted devices followed by a room temperature anneal. The use of ion implantation for the development of an accelerated ELDRS test method is proposed. This thesis demonstrated that hydrogen can be succesfully implanted into devices, established an upper bound for the LM124 for implantation and a lower bound for hydrogen remaining in the target area and the effect of hydrogen implantation on the AD590 temperature transducer is discussed. This thesis concludes by suggesting hydrogen implantation as a method for use by manufacturers during the design and investigation of intrinsically ELDRS-free technologies.

Change in Practice over Four Decades in the Management of Graves' Disease in Scotland.

PubMed

Smith, D M; Dutta, S; Ahmed, F; Thaha, M A

2016-01-01

There is continuing debate on the optimal treatment for Grave's thyrotoxicosis with a resultant variation in clinical practice. The present study aimed to ascertain changes in practice in the treatment of Grave's thyrotoxicosis in Tayside, Scotland, over the past four decades. Methods. The "Scottish automated follow-up register" (SAFUR) was queried to identify all patients treated for Grave's thyrotoxicosis from 1968 to 2007 inclusive. Patients were divided into 4 groups (Groups A to D) according to the decades. Demographic profile, treatment modalities, radioactive iodine (RAI) dose, and recurrence rates were studied and outcomes were compared by χ (2) test and ANOVA using SPSS v15.0. A p value of < 0.05 was considered significant. Results. Altogether, 3737 patients were diagnosed with Grave's thyrotoxicosis over the 4 decades. Use of RAI has increased from 43.1% in Group A to 68% in Group D (p < 0.001). The dose of RAI has increased (p < 0.001) and there has been a reduction in recurrence rate with higher dose of RAI. Surgical intervention rates decreased from 55.3% to 12.3% (p < 0.001) over time. Conclusions. Analysis of a large dataset of patients with Grave's thyrotoxicosis suggests increasing use of RAI as the preferred first line of treatment. Furthermore, using a single higher dose of RAI and adoption of total thyroidectomy have decreased recurrence rates.

Change in Practice over Four Decades in the Management of Graves' Disease in Scotland

PubMed Central

Smith, D. M.; Dutta, S.; Ahmed, F.; Thaha, M. A.

2016-01-01

There is continuing debate on the optimal treatment for Grave's thyrotoxicosis with a resultant variation in clinical practice. The present study aimed to ascertain changes in practice in the treatment of Grave's thyrotoxicosis in Tayside, Scotland, over the past four decades. Methods. The “Scottish automated follow-up register” (SAFUR) was queried to identify all patients treated for Grave's thyrotoxicosis from 1968 to 2007 inclusive. Patients were divided into 4 groups (Groups A to D) according to the decades. Demographic profile, treatment modalities, radioactive iodine (RAI) dose, and recurrence rates were studied and outcomes were compared by χ 2 test and ANOVA using SPSS v15.0. A p value of < 0.05 was considered significant. Results. Altogether, 3737 patients were diagnosed with Grave's thyrotoxicosis over the 4 decades. Use of RAI has increased from 43.1% in Group A to 68% in Group D (p < 0.001). The dose of RAI has increased (p < 0.001) and there has been a reduction in recurrence rate with higher dose of RAI. Surgical intervention rates decreased from 55.3% to 12.3% (p < 0.001) over time. Conclusions. Analysis of a large dataset of patients with Grave's thyrotoxicosis suggests increasing use of RAI as the preferred first line of treatment. Furthermore, using a single higher dose of RAI and adoption of total thyroidectomy have decreased recurrence rates. PMID:27313946

Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

PubMed

Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

2016-02-01

Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation

PubMed Central

Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

2016-01-01

Abstract Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate. This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2 g/kg), a single dose of rituximab (375 mg/m2), and 4 doses of bortezomib (1.3 mg/m2). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients. There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83 ± 16.0 (14952 ± 5820) and 63 ± 36.0 (10321 ± 7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468–634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group. In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients. PMID:26844479

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

PubMed

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

2015-07-01

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

Risk for Valvular Heart Disease After Treatment for Hodgkin Lymphoma

PubMed Central

Cutter, David J.; Schaapveld, Michael; Darby, Sarah C.; Hauptmann, Michael; van Nimwegen, Frederika A.; Krol, Augustinus D. G.; Janus, Cecile P. M.; van Leeuwen, Flora E.

2015-01-01

Background: Hodgkin lymphoma (HL) survivors are at increased risk for developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response. Methods: A case-control study was nested in a cohort of 1852 five-year HL survivors diagnosed at ages 15 to 41 years and treated between 1965 and 1995. Case patients had VHD of at least moderate severity as their first cardiovascular diagnosis following HL treatment. Control patients were matched to case patients for age, gender, and HL diagnosis date. Treatment and follow-up data were abstracted from medical records. Radiation doses to heart valves were estimated by reconstruction of individual treatments on representative computed tomography datasets. All statistical tests were two-sided. Results: Eighty-nine case patients with VHD were identified (66 severe or life-threatening) and 200 control patients. Aortic (n = 63) and mitral valves (n = 42) were most frequently affected. Risks increased more than linearly with radiation dose. For doses to the affected valve(s) of less than or equal to 30, 31–35, 36–40, and more than 40 Gy, VHD rates increased by factors of 1.4, 3.1, 5.4, and 11.8, respectively (P trend < .001). Approximate 30-year cumulative risks were 3.0%, 6.4%, 9.3%, and 12.4% for the same dose categories. VHD rate increased with splenectomy by a factor of 2.3 (P = .02). Conclusions: Radiation dose to the heart valves can increase the risk for clinically significant VHD, especially at doses above 30 Gy. However, for patients with mediastinal involvement treated today with 20 or 30 Gy, the 30-year risk will be increased by only about 1.4%. These findings may be useful for patients and doctors both before treatment and during follow-up. PMID:25713164

Risk of valvular heart disease after treatment for Hodgkin lymphoma.

PubMed

Cutter, David J; Schaapveld, Michael; Darby, Sarah C; Hauptmann, Michael; van Nimwegen, Frederika A; Krol, Augustinus D G; Janus, Cecile P M; van Leeuwen, Flora E; Aleman, Berthe M P

2015-04-01

Hodgkin lymphoma (HL) survivors are at increased risk of developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response. A case-control study was nested in a cohort of 1852 five-year HL survivors diagnosed at ages 15 to 41 years and treated between 1965 and 1995. Case patients had VHD of at least moderate severity as their first cardiovascular diagnosis following HL treatment. Control patients were matched to case patients for age, gender, and HL diagnosis date. Treatment and follow-up data were abstracted from medical records. Radiation doses to heart valves were estimated by reconstruction of individual treatments on representative computed tomography datasets. All statistical tests were two-sided. Eighty-nine case patients with VHD were identified (66 severe or life-threatening) and 200 control patients. Aortic (n = 63) and mitral valves (n = 42) were most frequently affected. Risks increased more than linearly with radiation dose. For doses to the affected valve(s) of less than or equal to 30, 31-35, 36-40, and more than 40 Gy, VHD rates increased by factors of 1.4, 3.1, 5.4, and 11.8, respectively (P trend < .001). Approximate 30-year cumulative risks were 3.0%, 6.4%, 9.3%, and 12.4% for the same dose categories. VHD rate increased with splenectomy by a factor of 2.3 (P = .02). Radiation dose to the heart valves can increase the risk of clinically significant VHD, especially at doses above 30 Gy. However, for patients with mediastinal involvement treated today with 20 or 30 Gy, the 30-year risk will be increased by only about 1.4%. These findings may be useful for patients and doctors both before treatment and during follow-up. © The Author 2015. Published by Oxford University Press.

Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels.

PubMed

Schver, Giovanna C R M; Lee, Ping I

2018-05-07

Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates sufficiently rapid initial supersaturation buildup above the critical supersaturation, resulting in more rapid precipitation. Above this smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of drug release gets slower, which results in a more modest rate of supersaturation buildup, leading to a maximum supersaturation below the critical-supersaturation level without appreciable precipitation. The area-under-the-curve (AUC) values of the in vitro kinetic-solubility concentration-time profiles were used to correlate the corresponding trends in dissolution enhancement. There are observed monotonic increases in AUC values with increasing particle sizes for high-dose ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously reported AUC maxima at some intermediate supersaturation rates or doses in soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the critical dose levels), crystallization would be negligible, leading to sustained supersaturation with all particle sizes (i.e., eventually reaching the same maximum supersaturation) and the smallest particle size reaching the maximum supersaturation the fastest. As a result, the smallest particle sizes yield the largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel matrixes. In addition to probing the interplay between the supersaturation-generation rates and total doses in ASDs based on insoluble hydrogel carriers, our results further support the fact that through either increasing the hydrogel-particle size or lowering the total dose to achieve maximum supersaturation still below the critical-supersaturation level, it is possible to avoid drug precipitation so as to maintain sustained supersaturation.

Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

NASA Technical Reports Server (NTRS)

George, K. A.; Hada, M.; Patel, Z.; Huff, J.; Pluth, J. M.; Cucinotta, F. A.

2009-01-01

Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase, DNA-PK activity. Chromosomes were analyzed using the fluorescence in-situ hybridization (FISH) chromosome painting method in cells at the first division post-irradiation and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma radiation induced higher yields of both simple and complex exchanges in the DSB repair defective cells than in the normal cells. The quadratic dose-response terms for both chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further investigate the sensitivity differences for low and low high doses, we performed chronic low dose-rate irradiation, and have begun studies with ATM and Nibrin inhibitors and siRNA knockout of these proteins. Results support the conclusion that for the endpoint of simple chromosomal aberrations (translocation or dicentrics), the increased radiation sensitivity of AT cells found at high doses (>1 Gy) does not carry over to low doses or doserates, while NBS cells show increased sensitivity for both high and low dose exposures.

Assessment of dose and DNA damages in individuals exposed to low dose and low dose rate ionizing radiations during computed tomography imaging.

PubMed

Kanagaraj, Karthik; Abdul Syed Basheerudeen, Safa; Tamizh Selvan, G; Jose, M T; Ozhimuthu, Annalakshmi; Panneer Selvam, S; Pattan, Sudha; Perumal, Venkatachalam

2015-08-01

Computed tomography (CT) is a frequently used imaging modality that contributes to a tenfold increase in radiation exposure to the public when compared to other medical imaging modalities. The use of radiation for therapeutic need is always rationalized on the basis of risk versus benefit thereby increasing concerns on the dose received by patients undergoing CT imaging. Therefore, it was of interest to us to investigate the effects of low dose and low dose-rate X-irradiation in patients who underwent CT imaging by recording the doses received by the eye, forehead and thyroid, and to study the levels of damages in the lymphocytes in vivo. Lithium manganese borate doped with terbium (LMB:Tb) thermo luminescence dosimeters (TLD) were used to record the doses in the patient's (n = 27) eye, forehead, and thyroid and compared with the dose length product (DLP) values. The in vivo DNA damages measured were compared before and after CT imaging using chromosomal aberration (CA) and micronucleus (MN) assays. The overall measured organ dose ranged between 2 ± 0.29 and 520 ± 41.63 mGy for the eye, 0.84 ± 0.29 and 210 ± 20.50 mGy for the forehead, and 1.79 ± 0.43 and 185 ± 0.70 mGy for the thyroid. The in vivo damages measured from the blood lymphocytes of the subjects showed an extremely significant (p < 0.0001) increase in CA frequency and significant (p < 0.001) increase in MN frequency after exposure, compared to before exposure. The results suggest that CT imaging delivers a considerable amount of radiation dose to the eye, forehead, and thyroid, and the observed increase in the CA and MN frequencies show low dose radiation effects calling for protective regulatory measures to increase patient's safety. This study is the first attempt to indicate the trend of doses received by the patient's eye, forehead and thyroid and measured directly in contrast to earlier values obtained by extrapolation from phantoms, and to assess the in vivo low dose effects in an Indian patient population undergoing CT procedures. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation.

PubMed

Sanzari, Jenine K; Cengel, Keith A; Wan, X Steven; Rusek, Adam; Kennedy, Ann R

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure.

Acute hematological effects in mice exposed to the expected doses, dose-rates, and energies of solar particle event-like proton radiation

NASA Astrophysics Data System (ADS)

Sanzari, Jenine K.; Cengel, Keith A.; Steven Wan, X.; Rusek, Adam; Kennedy, Ann R.

2014-07-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during an SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hours post-radiation exposure.

Particle effects on ultraviolet disinfection of coliform bacteria in recycled water.

PubMed

Jolis, D; Lam, C; Pitt, P

2001-01-01

Pilot- and bench-scale coliform inactivation tests with UV irradiation were used to show how suspended solids remaining in filtered secondary effluent affect the efficiency of the UV disinfection process. Observed kinetic inactivation rates decreased with increasing suspended particle sizes of 7 microm or larger present in tertiary effluent. First-order inactivation rates estimated from collimated beam dose-response curves for discrete ranges of UV doses were substantially different, which should caution researchers not to compare inactivation data obtained with largely dissimilar UV doses or suspended particle distributions. A dose of approximately 800 J/m2 was identified as the minimum dose that will consistently meet the California wastewater reclamation coliform criterion when applied to in-line filtration effluent.

New monitoring by thermogravimetry for radiation degradation of EVA

NASA Astrophysics Data System (ADS)

Boguski, J.; Przybytniak, G.; Łyczko, K.

2014-07-01

The radiation ageing of ethylene vinyl-acetate copolymer (EVA) as the jacket of cable applied in nuclear power plant was carried out by gamma rays irradiation, and the degradation was monitored by a thermo-gravimetric analysis (TGA). The EVA decomposition rate in air by the isothermal at 400 °C decreased with increase of dose and also with decrease of the dose rate. The behavior of EVA jacket of cable indicated that the decomposition rate at 400 °C was reduced with increase of oxidation. The elongation at break by tensile test for the radiation aged EVA was closely related to the decomposition rate at 400 °C; therefore, the TGA might be applied for a diagnostic technique of the cable degradation.

Metabolism of isotretinoin. Biliary excretion of isotretinoin glucuronide in the rat.

PubMed

Meloche, S; Besner, J G

1986-01-01

The biliary metabolites of isotretinoin were examined after iv administration of 4-20-mg/kg doses to vitamin A-normal bile duct-cannulated rats. Analysis of bile by reverse phase high performance liquid chromatography showed that injection of isotretinoin is followed by a rapid excretion of metabolites in bile. Isotretinoin glucuronide was identified as the major metabolite in bile. A specific high performance liquid chromatography method based on the assay of generated isotretinoin in beta-glucuronidase-treated bile was developed for the determination of isotretinoin glucuronide in bile samples. The excretion rate of isotretinoin glucuronide increased rapidly to reach a maximum 55 min after dosing and then declined exponentially. After 330 min of collection, biliary excretion of isotretinoin glucuronide was almost complete, and the metabolite accounted for 34.8-37.9% of the dose. These results indicate that conjugation with glucuronic acid represents a major pathway for the metabolism of pharmacological doses of isotretinoin. The maximum excretion rate of isotretinoin glucuronide in bile increased in a linear manner with the dose of isotretinoin, and no delay was observed after the larger doses. These data suggest that glucuronidation and biliary excretion are not saturated at high pharmacological doses of isotretinoin.

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

PubMed

Hall, Matthew D; Schultheiss, Timothy E; Smith, David D; Fakih, Marwan G; Wong, Jeffrey Y C; Chen, Yi-Jen

2016-12-01

Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

Final product analysis in the e-beam and gamma radiolysis of aqueous solutions of metoprolol tartrate

NASA Astrophysics Data System (ADS)

Slegers, Catherine; Tilquin, Bernard

2006-09-01

The radiostability of metoprolol tartrate aqueous solutions and the influence of the absorbed dose (0-50 kGy), dose rate (e-beam (EB) vs. gamma ( γ)) and radioprotectors (pharmaceutical excipients) are investigated by HPLC-UV analyses and through computer simulations. The use of radioprotecting excipients is more promising than an increase in the dose rate to lower the degradation of metoprolol tartrate aqueous solutions for applications such as radiosterilization. The decontamination of metoprolol tartrate from waste waters by EB processing appears highly feasible.

Measurements of the Martian Gamma/Neutron Spectra with MSL/RAD

NASA Astrophysics Data System (ADS)

Kohler, J.; Zeitlin, C. J.; Ehresmann, B.; Wimmer-Schweingruber, R. F.; Hassler, D.; Reitz, G.; Brinza, D.; Weigle, E.; Boettcher, S.; Burmeister, S.; Guo, J.; Martin-Garcia, C.; Boehm, E.; Posner, A.; Rafkin, S. C.; Kortmann, O.

2013-12-01

The Radiation Assessment Detector (RAD) onboard Mars Science Laboratory's rover curiosity measures the energetic charged and neutral particle spectra and the radiation dose rate on the Martian surface. An important factor for determining the biological impact of the Martian surface radiation is the specific contribution of neutrons, which possess a high biological effectiveness. In contrast to charged particles, neutrons and gamma rays are generally only measured indirectly. Their measurement is the result of a complex convolution of the incident particle spectrum with the measurement process. We apply an inversion method to calculate the gamma/neutron spectra from the RAD neutral particle measurements. Here we show first measurements of the Martian gamma/neutron spectra and compare them to theoretical predictions. We find that the shape of the gamma spectrum is very similar to the predicted one, but with a ~50% higher intensity. The measured neutron spectrum agrees well with prediction up to ~100 MeV, but shows a considerably increased intensity for higher energies. The measured neutron spectrum translates into a radiation dose rate of 25 μGy/day and a dose equivalent rate of 106 μSv/day. This corresponds to 10% of the total surface dose rate, and 15% of the biological relevant surface dose equivalent rate on Mars. Measuring the Martian neutron spectra is an essential step for determining the mutagenic influences to past or present life at or beneath the Martian surface as well as the radiation hazard for future human exploration, including the shielding design of a potential habitat. The contribution of neutrons to the dose equivalent increases considerably with shielding thickness, so our measurements provide an important figure to mitigate cancer risk.

Dependence of pentobarbital kinetics upon the dose of the drug and its pharmacodynamic effects.

PubMed

Kozlowski, K H; Szaykowski, A; Danysz, A

1977-01-01

Pentobarbital (PB), at dose range of 20--50 mg/kg, displays in rabbits non-linear, dose-dependent kinetics. Pharmacokinetics parameters of drug elimination depend largely upon the dose, while the distribution phase is dose-independent. The rate of disappearance of PB from the central compartment (plasma) decreases with the increase of the dose. The analysis of pharmacodynamic parameters has shown that this dose-dependent retardation of PB elimination is probably caused by an impairment of metabolic processes, resulting from disturbance of the circulatory system. A close correlation has been found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and beta.Vd(extrap), a coefficient proportional to the rate of metabolism of PB [23, 29]. The results indicate the necessity of considering the changes in the functional state of the organism, related to the action of a drug, in pharmacokinetic studies.

Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma.

PubMed

Ma, Jinbo; Wang, Zhaoyang; Wang, Chengde; Chen, Ercheng; Dong, Yaozong; Song, Yipeng; Wang, Wei; You, Dong; Jiang, Wei; Zang, Rukun

2017-02-01

To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose-escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation.

Prescription order risk factors for pediatric dosing alerts.

PubMed

Stultz, J S; Porter, K; Nahata, M C

2015-02-01

To determine dosing alert rates based on prescription order characteristics and identify prescription order risk factors for the occurrence of dosing alerts. A retrospective analysis of inpatient medication orders and dosing alerts occurring during October 2011 and January, April, and July 2012 at a pediatric institution. Prescription orders and alerts were categorized by: medication class, patient age, route of administration, and month of the year. There were 228,259 orders during the studied period, with 11,072 alerted orders (4.9%). The most frequently alerted medication class was the non-analgesic central nervous system agent class (14% of alerts). Age, route, medication class, and month all independently affected dosing alert rates. The alert rate was highest for immunosuppressive agents (54%), neonates (6.7%), and orders for rectal administration (9.5%). The alert rate was higher in adult patients receiving their care at a pediatric institution (5.7%) compared to children (4.7%), but after multivariate analysis, pediatric orders had higher odds for an alert (OR 1.1, 95% CI 1.05-1.16). Mercaptopurine had the highest alert rate when categorized by active ingredient (73.9%). Albuterol 2.5mg/mL continuous aerosol and heparin 1000 units in 0.9% sodium chloride injection solution were the unique medications with the highest alert rates (100.0% and 97.7%, respectively). Certain types of prescription orders have a higher risk for causing dosing alerts than others. Patient age, medication class, route of administration, and the month of year can affect dosing alert rates. Design and customization efforts should focus on these medications and prescription order characteristics that increase the risk for dosing alerts. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Radiation dose reduction efficiency of buildings after the accident at the Fukushima Daiichi Nuclear Power Station.

PubMed

Monzen, Satoru; Hosoda, Masahiro; Osanai, Minoru; Tokonami, Shinji

2014-01-01

Numerous radionuclides were released from the Fukushima Daiichi Nuclear Power Station (F1-NPS) in Japan following the magnitude 9.0 earthquake and tsunami on March 11, 2011. Local residents have been eager to calculate their individual radiation exposure. Thus, absorbed dose rates in the indoor and outdoor air at evacuation sites in the Fukushima Prefecture were measured using a gamma-ray measuring devices, and individual radiation exposure was calculated by assessing the radiation dose reduction efficiency (defined as the ratio of absorbed dose rate in the indoor air to the absorbed dose rate in the outdoor air) of wood, aluminum, and reinforced concrete buildings. Between March 2011 and July 2011, dose reduction efficiencies of wood, aluminum, and reinforced concrete buildings were 0.55 ± 0.04, 0.15 ± 0.02, and 0.19 ± 0.04, respectively. The reduction efficiency of wood structures was 1.4 times higher than that reported by the International Atomic Energy Agency. The efficiency of reinforced concrete was similar to previously reported values, whereas that of aluminum structures has not been previously reported. Dose reduction efficiency increased in proportion to the distance from F1-NPS at 8 of the 18 evacuation sites. Time variations did not reflect dose reduction efficiencies at evacuation sites although absorbed dose rates in the outdoor air decreased. These data suggest that dose reduction efficiency depends on structure types, levels of contamination, and evacuee behaviors at evacuation sites.

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

PubMed

Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

2016-08-01

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

MO-F-16A-02: Simulation of a Medical Linear Accelerator for Teaching Purposes

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

Carlone, M; Lamey, M; Anderson, R

Purpose: Detailed functioning of linear accelerator physics is well known. Less well developed is the basic understanding of how the adjustment of the linear accelerator's electrical components affects the resulting radiation beam. Other than the text by Karzmark, there is very little literature devoted to the practical understanding of linear accelerator functionality targeted at the radiotherapy clinic level. The purpose of this work is to describe a simulation environment for medical linear accelerators with the purpose of teaching linear accelerator physics. Methods: Varian type lineacs were simulated. Klystron saturation and peak output were modelled analytically. The energy gain of anmore » electron beam was modelled using load line expressions. The bending magnet was assumed to be a perfect solenoid whose pass through energy varied linearly with solenoid current. The dose rate calculated at depth in water was assumed to be a simple function of the target's beam current. The flattening filter was modelled as an attenuator with conical shape, and the time-averaged dose rate at a depth in water was determined by calculating kerma. Results: Fifteen analytical models were combined into a single model called SIMAC. Performance was verified systematically by adjusting typical linac control parameters. Increasing klystron pulse voltage increased dose rate to a peak, which then decreased as the beam energy was further increased due to the fixed pass through energy of the bending magnet. Increasing accelerator beam current leads to a higher dose per pulse. However, the energy of the electron beam decreases due to beam loading and so the dose rate eventually maximizes and the decreases as beam current was further increased. Conclusion: SIMAC can realistically simulate the functionality of a linear accelerator. It is expected to have value as a teaching tool for both medical physicists and linear accelerator service personnel.« less

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

PubMed

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

2016-11-08

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

SU-E-T-13: Comparison of Dose Rates with and without Gold Backing of USC #9 Radioactive Eye Plaque Using MCNP5.

PubMed

Aryal, P; Molloy, J

2012-06-01

To show the effect of gold backing on dose rates for the USC #9 radioactive eye plaque. An I125 source (IsoAid model IAI-125A) and gold backing was modeled using MCNP5 Monte Carlo code. A single iodine seed was simulated with and without gold backing. Dose rates were calculated in two orthogonal planes. Dose calculation points were structured in two orthogonal planes that bisect the center of the source. A 2×2 cm matrix of spherical points of radius 0.2 mm was created in a water phantom of 10 cm radius. 0.2 billion particle histories were tracked. Dose differences with and without the gold backing were analyzed using Matlab. The gold backing produced a 3% increase in the dose rate near the source surface (<1mm) relative to that without the backing. This was presumably caused by fluorescent photons from the gold. At distances between 1 and 2 cm, the gold backing reduced the dose rate by up to 12%, which we attribute to a lack of scatter resulting from the attenuation from the gold. Dose differences were most pronounced in the radial direction near the source center but off axis. The dose decreased by 25%, 65% and 81% at 1, 2, and 3 mm off axis at a distance of 1 mm from the source surface. These effects were less pronounced in the perpendicular dimension near the source tip, where maximum dose decreases of 2% were noted. I 125 sources embedded directly into gold troughs display dose differences of 2 - 90%, relative to doses without the gold backing. This is relevant for certain types of plaques used in treatment of ocular melanoma. Large dose reductions can be observed and may have implications for scleral dose reduction. © 2012 American Association of Physicists in Medicine.

Mixing an energy drink with an alcoholic beverage increases motivation for more alcohol in college students.

PubMed

Marczinski, Cecile A; Fillmore, Mark T; Henges, Amy L; Ramsey, Meagan A; Young, Chelsea R

2013-02-01

There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmEDs) in social drinkers. It has been suggested that AmED beverages might lead individuals to drink greater quantities of alcohol. This experiment was designed to investigate whether the consumption of AmEDs would alter alcohol priming (i.e., increasing ratings of wanting another drink) compared with alcohol alone. Participants (n = 80) of equal gender attended 1 session where they were randomly assigned to receive 1 of 4 doses (0.91 ml/kg vodka, 1.82 ml/kg energy drink, 0.91 ml/kg vodka mixed with 1.82 ml/kg energy drink [AmED], or a placebo beverage). Alcohol-induced priming of the motivation to drink was assessed by self-reported ratings on the Desire for Drug questionnaire. The priming dose of alcohol increased the subjective ratings of "desire" for more alcohol, consistent with previous research that small doses of alcohol can increase the motivation to drink. Furthermore, higher desire ratings over time were observed with AmEDs compared with alcohol alone. Finally, ratings of liking the drink were similar for the alcohol and AmED conditions. An energy drink may elicit increased alcohol priming. This study provides laboratory evidence that AmED beverages may lead to greater motivation to drink versus the same amount of alcohol consumed alone. Copyright © 2012 by the Research Society on Alcoholism.

Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome.

PubMed

Jones, Tiffanny; Ho, Jacqueline R; Gualtieri, Marc; Bruno-Gaston, Janet; Chung, Karine; Paulson, Richard J; Bendikson, Kristin A

2018-01-01

To compare time to ovulation, ovulation rates, and side effect profile of traditional and the stair-step protocol for ovulation induction using clomiphene citrate in women with polycystic ovary syndrome (PCOS). We performed a retrospective study of women seeking care for infertility with a diagnosis of PCOS at a university-based infertility clinic from July 2012 to July 2014. We included patients who were resistant to the initial starting dose of 50 mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes included ovulation rates, clinical pregnancy rates, and mild and moderate-to-severe side effects based on dose. For the traditional protocol, higher doses of clomiphene were used each subsequent month if no ovulation occurred. For the stair-step protocol, higher doses of clomiphene were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. Our study had 80% power to detect a 20% difference in ovulation. One hundred nine patients were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%) in the stair-step protocol. Age and body mass index were similar between groups. The time to ovulation was decreased in the stair-step protocol group compared with the traditional protocol group (23.1±0.9 days vs 47.5±6.3 days). Ovulation rates were increased in the stair-step group compared with the traditional group at 150 mg (16 [37%] vs 8 [12%], P=.004) and at 200 mg (9 [21%] vs 3 [5%], P=.01). Pregnancy rates were similar between groups once ovulation was achieved (12 [18.1%] vs 7 [16.3%], P=.08). The stair-step protocol had an increased incidence of mild side effects (vasomotor flushes, headaches, gastrointestinal disturbance, mastalgia, changes in mood; 18 [41%] vs 8 [12%]), but there was no difference in the incidence of severe side effects (headaches, visual disturbances). For women with PCOS, the stair-step clomiphene protocol is associated with decreased time to ovulation and increased ovulation rates at higher doses when compared with the traditional protocol.

Human Papillomavirus Vaccine Coverage and Prevalence of Missed Opportunities for Vaccination in an Integrated Healthcare System.

PubMed

Irving, Stephanie A; Groom, Holly C; Stokley, Shannon; McNeil, Michael M; Gee, Julianne; Smith, Ning; Naleway, Allison L

2018-03-01

Human papillomavirus (HPV) vaccination has been recommended in the United States for female and male adolescents since 2006 and 2011, respectively. Coverage rates are lower than those for other adolescent vaccines. The objective of this study was to evaluate an assessment and feedback intervention designed to increase HPV vaccination coverage and quantify missed opportunities for HPV vaccine initiation at preventive care visits. We examined changes in HPV vaccination coverage and missed opportunities within the adolescent (11-17 years) population at 9 Oregon-based Kaiser Permanente Northwest outpatient clinics after an assessment and feedback intervention. Quarterly coverage rates were calculated for the adolescent populations at the clinics, according to age group (11-12 and 13-17 years), sex, and department (Pediatrics and Family Medicine). Comparison coverage assessments were calculated at 3 nonintervention (control) clinics. Missed opportunities for HPV vaccine initiation, defined as preventive care visits in which a patient eligible for HPV dose 1 remained unvaccinated, were examined according to sex and age group. An average of 29,021 adolescents were included in coverage assessments. Before the intervention, 1-dose and 3-dose quarterly coverage rates were increasing at intervention as well as at control clinics in both age groups. Postimplementation quarterly trends in 1-dose or 3-dose coverage did not differ significantly between intervention and control clinics for either age group. One-dose coverage rates among adolescents with Pediatrics providers were significantly higher than those with Family Medicine providers (56% vs 41% for 11- to 12-year-old and 82% vs 69% for 13- to 17-year-old girls; 55% vs 40% for 11- to 12-year-old and 78% vs 62% for 13- to 17-year-old boys). No significant differences in HPV vaccine coverage were identified at intervention clinics. However, coverage rates were increasing before the start of the intervention and might have been influenced by ongoing health system best practices. HPV vaccine coverage rates varied significantly according to department, which could allow for targeted improvement opportunities. Copyright © 2017 Academic Pediatric Association. All rights reserved.

Effect of the gamma radiation dose rate on psychrotrophic bacteria, thiobarbituric acid reactive substances, and sensory characteristics of mechanically deboned chicken meat.

PubMed

Brito, Poliana P; Azevedo, Heliana; Cipolli, Kátia M V A B; Fukuma, Henrique T; Mourão, Gerson B; Roque, Cláudio V; Miya, Norma T; Pereira, José L

2011-03-01

Frozen samples of mechanically deboned chicken meat (MDCM) with skin were irradiated with gamma radiation doses of 0.0 kGy (control) and 3 kGy at 2 different radiation dose rates: 0.32 kGy/h (3 kGy) and 4.04 kGy/h (3 kGy). Batches of irradiated and control samples were evaluated during 11 d of refrigerated (2 ± 1 °C) storage for the following parameters: total psychrotrophic bacteria count, thiobarbituric acid reactive substances (TBARS), evaluation of objective color (L*, a*, and b*) and a sensory evaluation (irradiated odor, oxidized odor, pink and brown colors). No statistical difference (P > 0.05) was found amongst the TBARS values obtained for the MDCM samples irradiated with dose rates of 0.32 and 4.04 kGy/h. There was a significant increase (P < 0.05) in the psychrotrophic bacterial count as from the 7th day of refrigerated storage, for the MDCM samples irradiated at the dose rate of 4.04 kGy/h. With respect to the attribute of oxidized odor, the samples irradiated with a dose rate of 0.32 kGy/h showed a stronger intensity and were significantly different (P < 0.05) from the sample irradiated with a dose rate of 4.04 kGy/h on days 0 and 2 of refrigerated storage. Irradiation with a dose rate of 4.04 kGy/h (3 kGy) was shown to be the best condition for the processing of MDCM according to the evaluation of all the variables, under the conditions of this study. Practical Application:  The results obtained for the application of different dose rates of ionizing radiation to mechanically deboned chicken meat will provide the food industry with information concerning the definition of the best processing conditions to maximize the sensory and food quality.

Dosimetric variations due to interfraction organ deformation in cervical cancer brachytherapy.

PubMed

Kobayashi, Kazuma; Murakami, Naoya; Wakita, Akihisa; Nakamura, Satoshi; Okamoto, Hiroyuki; Umezawa, Rei; Takahashi, Kana; Inaba, Koji; Igaki, Hiroshi; Ito, Yoshinori; Shigematsu, Naoyuki; Itami, Jun

2015-12-01

We quantitatively estimated dosimetric variations due to interfraction organ deformation in multi-fractionated high-dose-rate brachytherapy (HDRBT) for cervical cancer using a novel surface-based non-rigid deformable registration. As the number of consecutive HDRBT fractions increased, simple addition of dose-volume histogram parameters significantly overestimated the dose, compared with distribution-based dose addition. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The New Radiobiology: Returning to Our Roots

PubMed Central

Ulsh, Brant A.

2012-01-01

In 2005, two expert advisory bodies examined the evidence on the effects of low doses of ionizing radiation. The U.S. National Research Council concluded that current scientific evidence is consistent with the linear no-threshold dose-response relationship (NRCNA 2005) while the French National Academies of Science and Medicine concluded the opposite (Aurengo et al. 2005). These contradictory conclusions may stem in part from an emphasis on epidemiological data (a “top down” approach) versus an emphasis on biological mechanisms (a “bottom up” approach). In this paper, the strengths and limitations of the top down and bottom up approaches are discussed, and proposals for strengthening and reconciling them are suggested. The past seven years since these two reports were published have yielded increasing evidence of nonlinear responses of biological systems to low radiation doses delivered at low dose-rates. This growing body of evidence is casting ever more doubt on the extrapolation of risks observed at high doses and dose-rates to estimate risks associated with typical environmental and occupational exposures. This paper compares current evidence on low dose, low dose-rate effects against objective criteria of causation. Finally, some questions for a post-LNT world are posed. PMID:23304107

[Determination of radioactivity by smartphones].

PubMed

Hartmann, H; Freudenberg, R; Andreeff, M; Kotzerke, J

2013-01-01

The interest in the detection of radioactive materials has strongly increased after the accident in the nuclear power plant Fukushima and has led to a bottleneck of suitable measuring instruments. Smartphones equipped with a commercially available software tool could be used for dose rate measurements following a calibration according to the specific camera module. We examined whether such measurements provide reliable data for typical activities and radionuclides in nuclear medicine. For the nuclides 99mTc (10 - 1000 MBq), 131I (3.7 - 1800 MBq, therapy capsule) and 68Ga (50 - 600 MBq) radioactivity with defined geometry in different distances was measured. The smartphones Milestone Droid 1 (Motorola) and HTC Desire (HTC Corporation) were compared with the standard instruments AD6 (automess) and DoseGUARD (AEA Technology). Measurements with the smartphones and the other devices show a good agreement: linear signal increase with rising activity and dose rate. The long time measurement (131I, 729 MBq, 0.5 m, 60 min) demonstrates a considerably higher variation (by 20%) of the measured smartphone data values compared with the AD6. For low dose rates (< 1 µGy/h), the sensitivity decreases so that measurements of e. g. the natural radiation exposure do not lead to valid results. The calibration of the camera responsivity for the smartphone has a big influence on the results caused by the small detector surface of the camera semiconductor. With commercial software the camera module of a smartphone can be used for the measurement of radioactivity. Dose rates resulting from typical nuclear medicine procedures can be measured reliably (e. g., dismissal dose after radioiodine therapy). The signal shows a high correlation to measured values of conventional dose measurement devices.

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.

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

Human abuse liability assessment of oxycodone combined with ultra-low-dose naltrexone.

PubMed

Tompkins, David Andrew; Lanier, Ryan K; Harrison, Joseph A; Strain, Eric C; Bigelow, George E

2010-07-01

Prescription opioid abuse has risen dramatically in the United States as clinicians have increased opioid prescribing for alleviation of both acute and chronic pain. Opioid analgesics with decreased risk for abuse are needed. Preclinical and clinical studies have shown that opioids combined with ultra-low-dose naltrexone (NTX) may have increased analgesic potency and have suggested reduced abuse or dependence liability. This study addressed whether addition of ultra-low-dose naltrexone might decrease the abuse liability of oxycodone (OXY) in humans. This double-blind, placebo-controlled study systematically examined the subjective and physiological effects of combining oral OXY and ultra-low NTX doses in 14 experienced opioid abusers. Seven acute drug conditions given at least 5 days apart were compared in a within-subject crossover design: placebo, OXY 20 mg, OXY 40 mg, plus each of the active OXY doses combined with 0.0001 and 0.001 mg NTX. The methods were sensitive to detecting opioid effects on abuse liability indices, with significant differences between all OXY conditions and placebo as well as between 20 and 40 mg OXY doses on positive subjective ratings (e.g., "I feel a good drug effect" or "I like the drug"), on observer- and participant-rated opioid agonist effects, and on a drug-versus-money value rating. There were no significant differences or evident trends associated with the addition of either NTX dose on any abuse liability indices. The addition of ultra-low-dose NTX to OXY did not decrease abuse liability of acutely administered OXY in experienced opioid abusers.

SU-F-I-40: Impact of Scan Length On Patient Dose in Abdomen/pelvis CT Diagnosis

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

Park, I; Song, J; Kim, K

Purpose: To analysis the impact of scan length on patient doses in abdomen/pelvis CT diagnosis of each hospital. Methods: Scan length of 7 hospitals from abdomen/pelvis CT diagnosis was surveyed in Korea. Surveyed scan lengths were additional distance above diaphragm and distance below pubic symphysis except for standard scan range between diaphragm and pubic symphysis. Patient dose was estimated for adult male and female according to scan length of each hospital. CT-Expo was used to estimate the patient dose under identical equipment settings (120 kVp, 100 mAs, 10 mm collimation width, etc.) except scan length. Effective dose was calculated bymore » using tissue weighting factor of ICRP 103 recommendation. Increase rate of effective dose was calculated comparing with effective dose of standard scan range Results: Scan lengths of abdomen/pelvis CT diagnosis of each hospital were different. Also effective dose was increased with increasing the scan length. Generally increasing the distance above diaphragm caused increase of effective dose of male and female, but increasing the distance below pubic symphysis caused increase of effective dose of male. Conclusion: We estimated the patient dose according to scan length of each hospital in abdomen/pelvis CT diagnosis. Effective dose was increased by increasing the scan length because dose of organs with high tissue weighting factor such as lung, breast, testis were increased. Scan length is important factor on patient dose in CT diagnosis. If radiologic technologist interested in patient dose, decreasing the unnecessary scan length will decrease the risk of patients from radiation. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI13C0004).« less

Excess processing of oxidative damaged bases causes hypersensitivity to oxidative stress and low dose rate irradiation.

PubMed

Yoshikawa, Y; Yamasaki, A; Takatori, K; Suzuki, M; Kobayashi, J; Takao, M; Zhang-Akiyama, Q-M

2015-10-01

Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in Escherichia coli (E. coli) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the effects and the mechanisms of other radiation, such as low dose rate radiation, heavy-ion beams, or hydrogen peroxide (H2O2), are still poorly understood. In the present study, we constructed a stable HeLaS3 cell line overexpressing human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) protein. We determined the survival of HeLaS3 and HeLaS3/hOGG1 cells exposed to UV, heavy-ion beams, γ-rays, and H2O2. The results showed that HeLaS3 cells overexpressing hOGG1 were more sensitive to γ-rays, OH(•), and H2O2, but not to UV or heavy-ion beams, than control HeLaS3. We further determined the levels of 8-oxoG foci and of chromosomal double-strand breaks (DSBs) by detecting γ-H2AX foci formation in DNA. The results demonstrated that both γ-rays and H2O2 induced 8-oxoguanine (8-oxoG) foci formation in HeLaS3 cells. hOGG1-overexpressing cells had increased amounts of γ-H2AX foci and decreased amounts of 8-oxoG foci compared with HeLaS3 control cells. These results suggest that excess hOGG1 removes the oxidatively damaged 8-oxoG in DNA more efficiently and therefore generates more DSBs. Micronucleus formation also supported this conclusion. Low dose-rate γ-ray effects were also investigated. We first found that overexpression of hOGG1 also caused increased sensitivity to low dose rate γ-ray irradiation. The rate of micronucleus formation supported the notion that low dose rate irradiation increased genome instability.

Efficacy and Safety of Escalation of Adalimumab Therapy to Weekly Dosing in Pediatric Patients with Crohn's Disease.

PubMed

Dubinsky, Marla C; Rosh, Joel; Faubion, William A; Kierkus, Jaroslaw; Ruemmele, Frank; Hyams, Jeffrey S; Eichner, Samantha; Li, Yao; Huang, Bidan; Mostafa, Nael M; Lazar, Andreas; Thakkar, Roopal B

2016-04-01

The efficacy of adalimumab in inducing and maintaining remission in children with moderately to severely active Crohn's disease was shown in the IMAgINE 1 trial (NCT00409682). As per protocol, nonresponders or patients experiencing flare(s) on every other week (EOW) maintenance dosing could escalate to weekly dosing; we aimed to determine the therapeutic benefits of weekly dose escalation in this subpopulation. Week 52 remission and response rates were assessed in patients who escalated to weekly dosing from their previous EOW schedule, which was according to randomized treatment dose (higher dose [HD] adalimumab [≥40 kg, 40 mg EOW; <40 kg, 20 mg EOW] or lower dose [LD; ≥40 kg, 20 mg EOW; <40 kg, 10 mg EOW]). Adverse events were reported for patients remaining on EOW dosing and patients receiving weekly dosing. Escalation to weekly dosing occurred in 48/95 (50.5%) patients randomized to LD and 35/93 (37.6%) patients randomized to HD adalimumab (P = 0.076). Week 52 remission and response rates were 18.8% and 47.9% for patients receiving LD adalimumab weekly and 31.4% and 57.1% for patients receiving HD adalimumab weekly, respectively (LD versus HD, P = 0.19 for remission; P = 0.41 for response). Adverse event rates were similar for patients receiving EOW and weekly adalimumab. Weekly adalimumab dosing was clinically beneficial for children with Crohn's disease who experienced nonresponse or flare on EOW dosing. No increased safety risks were observed with weekly dosing.

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

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial.

PubMed

McAfee, Tim; Davis, Kevin C; Shafer, Paul; Patel, Deesha; Alexander, Robert; Bunnell, Rebecca

2017-01-01

While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose-response from the campaign was only assessed by self-report. Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. A 3-month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard-dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non-smokers and further increasing quit attempts among smokers, especially African-Americans. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Poster — Thur Eve — 36: Implementation of constant dose rate and gantry speed arc therapy(CDR-CAS-IMAT) for thoracic esophageal carcinoma on Varian 23EX

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

Zhang, Ruohui; Department of Medical Physics, Medical Faculty Mannheim, Heidelberg University; Fan, Xiaomei

2014-08-15

Objective: The purpose of this study is to propose an alternative planning approach for VMAT using constant dose rate and gantry speed arc therapy(CDR-CAS-IMAT) implementation on conventional Linac Varian 23EX and used IMRT as a benchmark to evaluate the performance. Methods and materials: Eighteen patients with thoracic esophageal carcinoma who were previously treated with IMRT on Varian 23EX were retrospectively planned for CDR-CAS-IMAT plans. Dose prescription was set to 60 Gy to PTVs in 30 fractions. The planning objectives for PTVs and OAR were corresponding with the IMRT plans. Dose to the PTVs and OAR were compared to IMRT withmore » respect to plan quality, MU, treatment time and delivery accuracy. Results: CDR-CAS-IMAT plans led to equivalent or superior plan quality as compared to IMRT, PTV's CI relative increased 16.2%, while small deviations were observed on minimum dose for PTV. Volumes in the cord receiving 40Gy were increased from 3.6% with IMRT to 7.0%. Treatment times were reduced significantly with CDR-CAS-IMAT(mean 85.7s vs. 232.1s, p < .05), however, MU increased by a factor of 1.3 and lung V10/5/3.5/aver were relative increase 6.7%,12%,17.9%,4.2%, respectively. And increased the E-P low dose area volume decreased the hight dose area. There were no significant difference in Delta4 measurements results between both planning techniques. Conclusion: CDR-CAS-IMAT plans can be implemented smoothly and quickly into a busy cancer center, which improved PTV CI and reduces treatment time but increased the MU and low dose irradiated area. An evaluation of weight loss must be performed during treatment for CDR-CAS-IMAT patients.« less

The use of prostaglandins in controlling estrous cycle of the ewe: a review.

PubMed

Fierro, Sergio; Gil, Jorge; Viñoles, Carolina; Olivera-Muzante, Julio

2013-02-01

This review considers the use of prostaglandin F(2α) and its synthetic analogues (PG) for controlling the estrous cycle of the ewe. Aspects such as phase of the estrus cycle, PG analogues, PG doses, ovarian follicle development pattern, CL formation, progesterone synthesis, ovulation rate, sperm transport, embryo quality, and fertility rates after PG administration are reviewed. Furthermore, protocols for estrus synchronization and their success in timed AI programs are discussed. Based on available information, the ovine CL is refractory to PG treatment for up to 2 days after ovulation. All PG analogues are effective when an appropriate dose is given; in that regard, there is a positive association between the dose administered and the proportion of ewes detected in estrus. Follicular response after PG is dependent on the phase of the estrous cycle at treatment. Altered sperm transport and low pregnancy rates are generally reported. However, reports on alteration of the steroidogenic capacity of preovulatory follicles, ovulation rate, embryo quality, recovery rates, and prolificacy, are controversial. Although various PG-based protocols can be used for estrus synchronization, a second PG injection improves estrus response when the stage of the estrous cycle at the first injection is unknown. The estrus cycle after PG administration has a normal length. Prostaglandin-based protocols for timed AI achieved poor reproductive outcomes, but increasing the interval between PG injections might increase pregnancy rates. Attempts to improve reproductive outcomes have been directed to provide a synchronized LH surge: use of different routes of AI (cervical or intrauterine), different PG doses, and increased intervals between PG injections. Finally we present our point of view regarding future perspectives on the use of PG in programs of controlled sheep reproduction. Copyright © 2013 Elsevier Inc. All rights reserved.

Radiation hardness study of semi-insulating GaAs detectors against 5 MeV electrons

NASA Astrophysics Data System (ADS)

Šagátová, A.; Zaťko, B.; Nečas, V.; Sedlačková, K.; Boháček, P.; Fülöp, M.; Pavlovič, M.

2018-01-01

A radiation hardness study of Semi-Insulating (SI) GaAs detectors against 5 MeV electrons is described in this paper. The influence of two parameters, the accumulative absorbed dose (from 1 to 200 kGy) and the applied dose rate (20, 40 or 80 kGy/h), on detector spectrometric properties were studied. The accumulative dose has influenced all evaluated spectrometric properties and also negatively affected the detector CCE (Charge Collection Efficiency). We have observed its systematic reduction from an initial 79% before irradiation down to about 51% at maximum dose of 200 kGy. Relative energy resolution was also influenced by electron irradiation. Its degradation was obvious in the range of doses from 24 up to a maximum dose of 200 kGy, where an increase from 19% up to 31% at 200 V reverse voltage was noticed. On the other hand, a global increase of detection efficiency with accumulative absorbed dose was observed for all samples. Concerning the actual detector degradation we can assume that the tested SI GaAs detectors will be able to operate up to a dose of 300 kGy at least, when irradiated by 5 MeV electrons. The second investigated parameter of irradiation, the dose rate of chosen ranges, did not greatly alter the spectrometric properties of studied detectors.

The effects of thyroxine on metabolism and water balance in a desert-dwelling rodent, Merriam's kangaroo rat (Dipodomys merriami).

PubMed

Banta, Marilyn R; Holcombe, Dale W

2002-01-01

Desert-dwelling mammals such as Merriam's kangaroo rat (Dipodomys merriani) need to conserve both energy and water to survive desert conditions characterized by aridity and low productivity. The thyroid hormone thyroxine increases both basal metabolic rate and urinary water loss in mammals. Increases in basal metabolism and urinary water loss are likely to be detrimental to D. merriami, therefore the regulation of this hormone may be important. To examine the effects of thyroxine in this species, we implanted adult kangaroo rats with pellets designed to release specific doses of thyroxine at a constant rate for 90 days or a placebo pellet. We measured plasma thyroxine concentration, basal metabolic rate, food consumption, urine concentration and water loss in all implanted animals. Thyroxine implants significantly increased both plasma thyroxine and basal metabolic rate in a relatively dose-dependent manner. In response to thyroxine. kangaroo rats increased food consumption only slightly, but this small increase was sufficient to compensate for their elevated metabolic rates. Neither urine concentration nor water loss varied among treatment groups. Thyroxine increased energy expenditure but not water loss in this species.

Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

PubMed Central

Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

2014-01-01

NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

Radiobiological equivalent of low/high dose rate brachytherapy and evaluation of tumor and normal responses to the dose.

PubMed

Manimaran, S

2007-06-01

The aim of this study was to compare the biological equivalent of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy in terms of the more recent linear quadratic (LQ) model, which leads to theoretical estimation of biological equivalence. One of the key features of the LQ model is that it allows a more systematic radiobiological comparison between different types of treatment because the main parameters alpha/beta and micro are tissue-specific. Such comparisons also allow assessment of the likely change in the therapeutic ratio when switching between LDR and HDR treatments. The main application of LQ methodology, which focuses on by increasing the availability of remote afterloading units, has been to design fractionated HDR treatments that can replace existing LDR techniques. In this study, with LDR treatments (39 Gy in 48 h) equivalent to 11 fractions of HDR irradiation at the experimental level, there are increasing reports of reproducible animal models that may be used to investigate the biological basis of brachytherapy and to help confirm theoretical predictions. This is a timely development owing to the nonavailability of sufficient retrospective patient data analysis. It appears that HDR brachytherapy is likely to be a viable alternative to LDR only if it is delivered without a prohibitively large number of fractions (e.g., fewer than 11). With increased scientific understanding and technological capability, the prospect of a dose equivalent to HDR brachytherapy will allow greater utilization of the concepts discussed in this article.

Effect of heating rate on thermoluminescence output of LiF: Mg, Ti (TLD-100) in dosimetric applications

NASA Astrophysics Data System (ADS)

Singh, Ranjit; Kainth, Harpreet Singh

2018-07-01

The luminiscence characteristics of thermoluminscence dosimeter LiF: Mg, Ti (TLD-100) irradiated to X-rays from 6 MV linac have been studied for wide range of 2-50 K/s readout linear heating rates. The reproducibility of glow curves for TLDs is found to be better at lower heating rates and depreciate at higher heating rates. The glow curve spectra were analysed using deconvolution procedure based on general-order kinetics. Shift in the peak maximum temperature per unit rise in heating rate for various peaks were found to decrease with heating rate. The TLDs irradiated with same dose exhibit decreasing TL counts with increase in the heating rate, which indicate the thermal quenching effect in TLD-100. The value of activation energy for each peak within the glow curve increases with heating rate. Calibration curves plotted for the dose range 0.4-1020 cGy exhibit decreasing slope with increasing readout heating rate. Corrections for temperature lag between the heating element and the dosimeter, and the effective heating rate (βeff) across the sample estimated using formulation proposed by Kitis and Tuyn and are found to be fairly applicable.

Increase in sensitivity of the baroreceptor reflex following microinjection of carbachol into the posterior hypothalamic nucleus of awake rats.

PubMed

Newey, C R; Martin, J R

2016-01-01

In a rat model, the baroreceptor reflex can be assessed by graded infusions of either phenylephrine or sodium nitroprusside with continuous hemodynamic monitoring. Microinjection of the cholinergic agonist carbachol (CCh) into the posterior hypothalamic nucleus (PHN) evokes an increase in mean arterial pressure and a change in heart rate. Lower doses of CCh evoke only tachycardia, whereas middle and higher doses evoke a biphasic change in heart rate of tachycardia followed by bradycardia. The bradycardia following the microinjection of CCh into the PHN can be attenuated by the previous administration of the vasopressin V1 receptor antagonist [d(CH2 )5 Tyr(Me)] arginine vasopressin (AVPX). Circulating arginine vasopressin (AVP) has been shown to increase the sensitivity of the baroreceptor reflex by stimulating vasopressin V1 receptors in the area postrema. The attenuation by AVPX of the bradycardia that results following the high doses of CCh suggests that AVP is released into the circulation following stimulation of cholinergic systems within the PHN. Thus, microinjection of a high dose of CCh (11 nmol) into the PHN alters the sensitivity of the baroreceptor reflex by increasing peripheral levels of AVP. © 2016 John Wiley & Sons Ltd.

Quantification of the Glycemic Response to Microdoses of Subcutaneous Glucagon at Varying Insulin Levels

PubMed Central

Castle, Jessica R.; Bakhtiani, Parkash A.; Haidar, Ahmad; Branigan, Deborah L.; Breen, Matthew; Ward, W. Kenneth

2014-01-01

OBJECTIVE Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. However, high insulin concentration lowers the hyperglycemic effect of glucagon, and small doses of glucagon in this setting are ineffective. There are no studies clearly defining the relationship between insulin levels, subcutaneous glucagon, and blood glucose. RESEARCH DESIGN AND METHODS Using a euglycemic clamp technique in 11 subjects with type 1 diabetes, we examined endogenous glucose production (EGP) of glucagon (25, 75, 125, and 175 μg) at three insulin infusion rates (0.016, 0.032, and 0.05 units/kg/h) in a randomized, crossover study. Infused 6,6-dideuterated glucose was measured every 10 min, and EGP was determined using a validated glucoregulatory model. Area under the curve (AUC) for glucose production was the primary outcome, estimated over 60 min. RESULTS At low insulin levels, EGP rose proportionately with glucagon dose, from 5 ± 68 to 112 ± 152 mg/kg (P = 0.038 linear trend), whereas at high levels, there was no increase in glucose output (19 ± 53 to 26 ± 38 mg/kg, P = NS). Peak glucagon serum levels and AUC correlated well with dose (r2 = 0.63, P < 0.001), as did insulin levels with insulin infusion rates (r2 = 0.59, P < 0.001). CONCLUSIONS EGP increases steeply with glucagon doses between 25 and 175 μg at lower insulin infusion rates. However, high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas. PMID:25139882

Quantification of the glycemic response to microdoses of subcutaneous glucagon at varying insulin levels.

PubMed

El Youssef, Joseph; Castle, Jessica R; Bakhtiani, Parkash A; Haidar, Ahmad; Branigan, Deborah L; Breen, Matthew; Ward, W Kenneth

2014-11-01

Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. However, high insulin concentration lowers the hyperglycemic effect of glucagon, and small doses of glucagon in this setting are ineffective. There are no studies clearly defining the relationship between insulin levels, subcutaneous glucagon, and blood glucose. Using a euglycemic clamp technique in 11 subjects with type 1 diabetes, we examined endogenous glucose production (EGP) of glucagon (25, 75, 125, and 175 μg) at three insulin infusion rates (0.016, 0.032, and 0.05 units/kg/h) in a randomized, crossover study. Infused 6,6-dideuterated glucose was measured every 10 min, and EGP was determined using a validated glucoregulatory model. Area under the curve (AUC) for glucose production was the primary outcome, estimated over 60 min. At low insulin levels, EGP rose proportionately with glucagon dose, from 5 ± 68 to 112 ± 152 mg/kg (P = 0.038 linear trend), whereas at high levels, there was no increase in glucose output (19 ± 53 to 26 ± 38 mg/kg, P = NS). Peak glucagon serum levels and AUC correlated well with dose (r2 = 0.63, P < 0.001), as did insulin levels with insulin infusion rates (r2 = 0.59, P < 0.001). EGP increases steeply with glucagon doses between 25 and 175 μg at lower insulin infusion rates. However, high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Dose response characteristics of polymethacrylic acid gel (PMAAG) for a polymerization-based dosimeter using NMR.

PubMed

Iskandar, S M; Elias, S; Jumiah, H; Asri, M T M; Masrianis, A; Ab Rahman, M Z; Taiman, K; Abdul Rashid, M Y

2004-05-01

The radiation-response characteristics of polymetharylic acid gel dosimeter prepared with different concentrations of monomer and cross-linker is described in these studies. The dosimeters were prepared under the hypoxic condition in a glove box and were then irradiated with gamma-rays produced by Co-60 radionuclide that was generated at 1.25MeV energy. The irradiation took place at different doses ranged from 0Gy to 19Gy. Due to the radiation activities, chain-reaction polymerisation processes had taken place in the formation of polymethacrylic acid (PMAA) gel, which cause the dose response mechanism increased in the NMR relaxation rates of protons. It has been observed that for higher concentration of monomer and cross-linker, the polymerization rate was increased.

Field Investigation of the Surface-deposited Radon Progeny as a Possible Predictor of the Airborne Radon Progeny Dose Rate

PubMed Central

Sun, Kainan; Steck, Daniel J.; Field, R. William

2009-01-01

The quantitative relationships between radon gas concentration, the surface-deposited activities of various radon progeny, the airborne radon progeny dose rate, and various residential environmental factors were investigated through actual field measurements in 38 selected Iowa houses occupied by either smokers or nonsmokers. Airborne dose rate was calculated from unattached and attached potential alpha energy concentrations (PAECs) using two dosimetric models with different activity-size weighting factors. These models are labeled Pdose and Jdose, respectively. Surface-deposited 218Po and 214Po were found significantly correlated to radon, unattached PAEC, and both airborne dose rates (p < 0.0001) in nonsmoking environments. However, deposited 218Po was not significantly correlated to the above parameters in smoking environments. In multiple linear regression analysis, natural logarithm transformation was performed for airborne dose rate as the dependent variable, as well as for radon and deposited 218Po and 214Po as predictors. An interaction effect was found between deposited 214Po and an obstacle in front of the Retrospective Reconstruction Detector (RRD) in predicting dose rate (p = 0.049 and 0.058 for Pdose and Jdose, respectively) for nonsmoking environments. After adjusting for radon and deposited radon progeny effects, the presence of either cooking, usage of a fireplace, or usage of a ceiling fan significantly, or marginal significantly, reduced the Pdose to 0.65 (90% CI 0.42–0.996), 0.54 (90% CI 0.28–1.02) and 0.66 (90% CI 0.45–0.96), respectively. For Jdose, only the usage of a ceiling fan significantly reduced the dose rate to 0.57 (90% CI 0.39–0.85). In smoking environments, deposited 218Po was a significant negative predictor for Pdose (RR 0.68, 90% CI 0.55–0.84) after adjusting for long-term 222Rn and environmental factors. A significant decrease of 0.72 (90% CI 0.64–0.83) in the mean Pdose was noted, after adjusting for the radon and radon progeny effects and other environmental factors, for every 10 increasing cigarettes smoked in the room. A significant increase of 1.71 in the mean Pdose was found for large room size relative to small room size (90% CI 1.08–2.79) after adjusting for the radon and radon progeny effects as well as other environmental factors. Fireplace usage was found to significantly increase the mean Pdose to 1.71 (90% CI 1.20–2.45) after adjusting for other factors. PMID:19590273

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

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

A highly infective plant-associated bacterium influences reproductive rates in pea aphids

PubMed Central

Hendry, Tory A.; Clark, Kelley J.; Baltrus, David A.

2016-01-01

Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction. PMID:26998321

A highly infective plant-associated bacterium influences reproductive rates in pea aphids.

PubMed

Hendry, Tory A; Clark, Kelley J; Baltrus, David A

2016-02-01

Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction.

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions

PubMed Central

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René

2015-01-01

Abstract Background: Spiromax® is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide–formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Methods: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Results: Mean values for both budesonide and formoterol were within 85%–115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. Conclusions: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment. PMID:26352860

Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death

PubMed Central

Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Hall, Kathi; Stein, C. Michael

2009-01-01

Background Users of typical antipsychotics have increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice. Methods We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotics in a retrospective cohort of Tennessee Medicaid enrollees. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonuser controls. To assess residual confounding related to antipsychotic indication, we performed a secondary analysis of antipsychotic users with no baseline diagnosis of schizophrenia or related psychoses, propensity-score matched with nonusers. Results Current users of both typical and atypical antipsychotics had greater rates of sudden cardiac death than did nonusers of any antipsychotic, with adjusted incidence-rate ratios (IRRs) of 2.00 (95% CI, 1.69–2.35) and 2.27 (1.89–2.73), respectively. Former antipsychotic users had no significantly increased risk (IRR = 1.13 [0.98–1.30]). For both classes of drugs, the risk for current users increased significantly with dose. For typical antipsychotics the IRRs increased from 1.31 (0.97–1.77) for low doses to 2.42 (1.91–3.06) for high doses (p<.001). For atypical agents the IRRs increased from 1.59 (1.03–2.46) for low doses to 2.86 (2.25–3.65) for high doses (p=.015). The IRR for atypical vs typical antipsychotics was 1.14 (.93–1.39). Similar findings were present in the propensity-score matched cohort. Conclusion Current users of both typical and atypical antipsychotics had a similar, dose-related increased risk of sudden cardiac death. PMID:19144938

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

NASA Astrophysics Data System (ADS)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

Immunogenicity of a three dose and five dose oral human rotavirus vaccine (RIX4414) schedule in south Indian infants.

PubMed

Kompithra, Rajeev Zachariah; Paul, Anu; Manoharan, Divya; Babji, Sudhir; Sarkar, Rajiv; Mathew, Leni G; Kang, Gagandeep

2014-08-11

This study was undertaken to compare the immunogenicity of a three dose and five dose schedule of an oral live-attenuated human rotavirus vaccine, Rotarix in south Indian infants. Healthy infants (N=90), six to seven weeks of age were enrolled to receive three doses (n=45) or five doses of Rotarix vaccine (n=45) along with other scheduled vaccines, each dose separated by a four week interval. Blood samples were taken before vaccination and one month post-dose three in the Rotarix three dose group and one month post-dose five in the Rotarix five dose group; all were tested for anti-rotavirus IgA by an antibody sandwich enzyme immunoassay. At baseline, >50% of infants had >20 units of anti-rotavirus IgA. The seroconversion rates after three and five doses were low and not significantly different in the two groups. However, among vaccine responders, children seropositive at baseline showed a much greater absolute increase in IgA antibody levels than children seronegative at baseline. Rotarix vaccine showed low immunogenicity in south Indian children and increasing the number of doses did not increase the proportion of infants seroconverting after vaccination. Copyright © 2014. Published by Elsevier Ltd.

Mortality among military participants at the 1957 PLUMBBOB nuclear weapons test series and from leukemia among participants at the SMOKY test.

PubMed

Caldwell, Glyn G; Zack, Matthew M; Mumma, Michael T; Falk, Henry; Heath, Clark W; Till, John E; Chen, Heidi; Boice, John D

2016-09-01

Health effects following low doses of ionizing radiation are uncertain. Military veterans at the Nevada test site (NTS) during the SMOKY atmospheric nuclear weapons test in 1957 were reported to be at increased risk for leukemia in 1979, but this increase was not evaluated with respect to radiation dose. The SMOKY test was one of 30 tests in 1957 within the PLUMBBOB test series. These early studies led to public laws where atomic veterans could qualify for compensation for presumptive radiogenic diseases. A retrospective cohort study was conducted of 12219 veterans at the PLUMBBOB test series, including 3020 at the SMOKY nuclear test. Mortality follow-up was through 2010 and observed causes of death were compared with expected causes based on general population rates. Radiation dose to red bone marrow was based on individual dose reconstructions, and Cox proportional hazards models were used to evaluate dose response for all leukemias other than chronic lymphocytic leukemia (non-CLL leukemia). Vital status was determined for 95.3% of the 12 219 veterans. The dose to red bone marrow was low (mean 3.2 mGy, maximum 500 mGy). Military participants at the PLUMBBOB nuclear test series remained relatively healthy after 53 years and died at a lower rate than the general population. In contrast, and in comparison with national rates, the SMOKY participants showed significant increases in all causes of death, respiratory cancer, leukemia, nephritis and nephrosis, and accidents, possibly related in part to lifestyle factors common to enlisted men who made up 81% of the SMOKY cohort. Compared with national rates, a statistically significant excess of non-CLL leukemia was observed among SMOKY participants (Standardized Mortality Ratio  =  1.89, 95% 1.24-2.75, n  =  27) but not among PLUMBBOB participants after excluding SMOKY (SMR  =  0.87, 95% 0.64-1.51, n  =  47). Leukemia risk, initially reported to be significantly increased among SMOKY participants, remained elevated, but this risk diminished over time. Despite an intense dose reconstruction, the risk for leukemia was not found to increase with increasing levels of radiation dose to the red bone marrow. Based on a linear model, the estimated excess relative risk per mGy is  -0.05 (95% CI -0.14, 0.04). An explanation for the observed excess of leukemia remains unresolved but conceivably could be related to chance due to small numbers, subtle biases in the study design and/or high tobacco use among enlisted men. Larger studies should elucidate further the possible relationship between fallout radiation, leukemia and cancer among atomic veterans.

Mortality among Military Participants at the 1957 PLUMBBOB Nuclear Weapons Test Series and on Leukemia among Participants at the SMOKY Test

PubMed Central

Caldwell, Glyn G.; Zack, Matthew M.; Mumma, Michael T.; Falk, Henry; Heath, Clark W.; Till, John E.; Chen, Heidi; Boice, John D.

2016-01-01

Health effects following low doses of ionizing radiation are uncertain. Military veterans at the Nevada Test Site (NTS) during the SMOKY atmospheric nuclear weapons test in 1957 were reported to be at increased risk for leukemia in 1979, but this increase was not evaluated with respect to radiation dose. The SMOKY test was one of 30 tests in 1957 within the PLUMBBOB test series. These early studies led to public laws where atomic veterans could qualify for compensation for presumptive radiogenic diseases. A retrospective cohort study was conducted of 12,219 veterans at PLUMBBOB test series, including 3,020 at the SMOKY nuclear test. Mortality follow-up was through 2010 and observed causes of death were compared with expected causes based on general population rates. Radiation dose to red bone marrow was based on individual dose reconstructions, and Cox proportional hazards models were used to evaluate dose response for all leukemias other than chronic lymphocytic leukemia (non-CLL leukemia). Vital status was determined for 95.3% of the 12,219 veterans. The dose to red bone marrow was low (mean 3.2 mGy, maximum 500 mGy). Military participants at the PLUMBBOB nuclear test series remained relatively healthy after 53 years and died at a lower rate than the general population. In contrast, and in comparison with national rates, the SMOKY participants showed significant increases in all causes of death, respiratory cancer, leukemia, nephritis and nephrosis, and accidents, possibly related in part to lifestyle factors common to enlisted men who made up 81% of the SMOKY cohort. Compared with national rates, a statistically significant excess of non-CLL leukemia was observed among SMOKY participants (Standardized Mortality Ratio=1.89, 95% 1.24–2.75, n=27) but not among PLUMBBOB participants after excluding SMOKY (SMR=0.87, 95% 0.64–1.51, n=47). Leukemia risk, initially reported to be significantly increased among SMOKY participants, remained elevated, but this risk diminished over time. Despite an intense dose reconstruction, the risk for leukemia was not found to increase with increasing levels of radiation dose to the red bone marrow. Based on a linear model, the estimated excess relative risk per mGy is −0.05 (95% CI −0.14, 0.04). An explanation for the observed excess of leukemia remains unresolved but conceivably could be related to chance due to small numbers, subtle biases in the study design and/or high tobacco use among enlisted men. Larger studies should elucidate further the possible relationship between fallout radiation, leukemia and cancer among atomic veterans. PMID:27355245

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

PubMed

Elefritz, Jessica L; Bauer, Karri A; Jones, Christian; Mangino, Julie E; Porter, Kyle; Murphy, Claire V

2017-09-01

Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

LEUKEMIA, LYMPHOMA AND MULTIPLE MYELOMA MORTALITY (1950–1999) AND INCIDENCE (1969–1999) IN THE ELDORADO URANIUM WORKERS COHORT

PubMed Central

Zablotska, Lydia B.; Lane, Rachel S.D.; Frost, Stanley E.; Thompson, Patsy A.

2014-01-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. PMID:24583244

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

PubMed

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

2004-07-01

Laser wakefield acceleration (LWFA) technology has evolved to where it should be evaluated for its potential as a future competitor to existing technology that produces electron and x-ray beams. The purpose of the present work is to investigate the dosimetric properties of an electron beam that should be achievable using existing LWFA technology, and to document the necessary improvements to make radiotherapy application for LWFA viable. This paper first qualitatively reviews the fundamental principles of LWFA and describes a potential design for a 30 cm accelerator chamber containing a gas target. Electron beam energy spectra, upon which our dose calculations are based, were obtained from a uniform energy distribution and from two-dimensional particle-in-cell (2D PIC) simulations. The 2D PIC simulation parameters are consistent with those reported by a previous LWFA experiment. According to the 2D PIC simulations, only approximately 0.3% of the LWFA electrons are emitted with an energy greater than 1 MeV. We studied only the high-energy electrons to determine their potential for clinical electron beams of central energy from 9 to 21 MeV. Each electron beam was broadened and flattened by designing a dual scattering foil system to produce a uniform beam (103%>off-axis ratio>95%) over a 25 x 25 cm2 field. An energy window (deltaE) ranging from 0.5 to 6.5 MeV was selected to study central-axis depth dose, beam flatness, and dose rate. Dose was calculated in water at a 100 cm source-to-surface distance using the EGS/BEAM Monte Carlo algorithm. Calculations showed that the beam flatness was fairly insensitive to deltaE. However, since the falloff of the depth-dose curve (R10-R90) and the dose rate both increase with deltaE, a tradeoff between minimizing (R10-R90) and maximizing dose rate is implied. If deltaE is constrained so that R10-R90 is within 0.5 cm of its value for a monoenergetic beam, the maximum practical dose rate based on 2D PIC is approximately 0.1 Gy min(-1) for a 9 MeV beam and 0.03 Gy min(-1) for a 15 MeV beam. It was concluded that current LWFA technology should allow a table-top terawatt (T3) laser to produce therapeutic electron beams that have acceptable flatness, penetration, and falloff of depth dose; however, the dose rate is still 1%-3% of that which would be acceptable, especially for higher-energy electron beams. Further progress in laser technology, e.g., increasing the pulse repetition rate or number of high energy electrons generated per pulse, is necessary to give dose rates acceptable for electron beams. Future measurements confirming dosimetric calculations are required to substantiate our results. In addition to achieving adequate dose rate, significant engineering developments are needed for this technology to compete with current electron acceleration technology. Also, the functional benefits of LWFA electron beams require further study and evaluation.

Inducing labor

MedlinePlus

... the cervix, and contractions may even begin. Your baby's heart rate will be monitored for a few hours. ... dose may be slowly increased as needed. Your baby's heart rate and the strength of your contractions will ...

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

PubMed

Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

2018-03-08

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Pilocarpine disposition and salivary flow responses following intravenous administration to dogs.

PubMed

Weaver, M L; Tanzer, J M; Kramer, P A

1992-08-01

Oral doses of pilocarpine increase salivary flow rates in patients afflicted with xerostomia (dry mouth). This study examined the pharmacokinetics of and a pharmacodynamic response (salivation) to intravenous pilocarpine nitrate administration in dogs. Disposition was linear over a dose range of 225-600 micrograms/kg; plasma concentrations were 10-120 micrograms/L. Elimination was rapid and generally biphasic, with a terminal elimination half-life of approximately 1.3 hr. The systemic clearance of pilocarpine was high (2.22 +/- 0.49 L/kg/hr) and its steady-state volume of distribution (2.30 +/- 0.64 L/kg) was comparable to that of many other basic drugs. All doses of pilocarpine induced measurable submaxillary and parotid salivary flow rates which could be maintained constant over time. Cumulative submaxillary saliva flow was linearly related to total pilocarpine dose. Plasma pilocarpine concentration was linearly related to both steady-state and postinfusion submaxillary salivary flow rates.

Asparagus stem as a new lignocellulosic biomass feedstock for anaerobic digestion: increasing hydrolysis rate, methane production and biodegradability by alkaline pretreatment.

PubMed

Chen, Xiaohua; Gu, Yu; Zhou, Xuefei; Zhang, Yalei

2014-07-01

Recently, anaerobic digestion of lignocellulosic biomass for methane production has attracted considerable attention. However, there is little information regarding methane production from asparagus stem, a typical lignocellulosic biomass, by anaerobic digestion. In this study, alkaline pretreatment of asparagus stem was investigated for its ability to increase hydrolysis rate and methane production and to improve biodegradability (BD). The hydrolysis rate increased with increasing NaOH dose, due to higher removal rates of lignin and hemicelluloses. However, the optimal NaOH dose was 6% (w/w) according to the specific methane production (SMP). Under this condition, the SMP and the technical digestion time of the NaOH-treated asparagus stem were 242.3 mL/g VS and 18 days, which were 38.4% higher and 51.4% shorter than those of the untreated sample, respectively. The BD was improved from 40.1% to 55.4%. These results indicate that alkaline pretreatment could be an efficient method for increasing methane production from asparagus stem. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

NASA Astrophysics Data System (ADS)

Yu, Kanglun; Doherty, Alison H.; Genik, Paula C.; Gookin, Sara E.; Roteliuk, Danielle M.; Wojda, Samantha J.; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E.; Weil, Michael M.; Donahue, Seth W.

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation.

Impact of a phenytoin loading dose program in the emergency department.

PubMed

Brancaccio, Adam; Giuliano, Christopher; McNorton, Kelly; Delgado, George

2014-11-01

The use of a combined physician-and pharmacist-directed phenytoin loading dose program in an emergency department (ED) was evaluated. This single-center, observational, preimplementation-postimplementation study evaluated adult patients who received a phenytoin loading dose in the ED. The primary outcome compared the proportion of optimal phenytoin loading doses in the preimplementation and postimplementation groups. The postimplementation group was further stratified into pharmacist- and prescriber-dosing groups. Other outcomes evaluated included the numbers of appropriate serum phenytoin concentrations measured, adverse drug reactions (ADRs), and recurrence of seizures within 24 hours of loading dose administration in the preimplementation and postimplementation groups. There was no difference in the proportion of optimal phenytoin loading doses between the preimplementation and postimplementation groups (50% versus 62%, respectively; p=0.19). When stratified by individual groups, the rate of optimal phenytoin loading doses increased by 64% in the postimplementation pharmacist group (50% versus 82%, p=0.007), while the rate in the prescriber-dosing group remained relatively unchanged (50% versus 49%, p=0.91). The number of appropriate serum phenytoin concentrations significantly improved in the postimplementation versus preimplementation group (65% versus 40%, p=0.025). Rates of ADRs and recurrence of seizures did not differ across the study groups. No change in the percentage of optimal phenytoin loading doses in the ED was observed after implementation of a combined pharmacist- and physician- dosing program. When stratified into pharmacist or prescriber dosing, the pharmacist-led dosing program significantly improved the proportion of patients who received optimal phenytoin loading doses. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation

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

Speiser, B.L.; Spratling, L.

The purpose of the study was to describe a new clinical entity observed in follow-up bronchoscopies in patients who were treated with high dose rate and medium dose rate remote afterloading brachytherapy of the tracheobronchial tree. Patients were treated by protocol with medium dose rate, 47 patients receiving 1000 cGy at a 5 mm depth times three fractions, high dose rate 144 patients receiving 1000 cGy at a 10 mm depth for three fractions and high dose rate 151 patients receiving cGy at a 10 mm depth for three fractions followed by bronchoscopy. Incidence of this entity was 9% formore » the first group, 12% for the second, and 13% for the third group. Reactions were grade 1 consisting of mild inflammatory response with a partial whitish circumferential membrane in an asymptomatic patient; grade 2, thicker complete white circumferential membrane with cough and/or obstructive problems requiring intervention; grade 3, severe inflammatory response with marked membranous exudate and mild fibrotic reaction; and grade 4 a predominant fibrotic reaction with progressive stenosis. Variables associated with a slightly increased incidence of radiation bronchitis and stenosis included: large cell carcinoma histology, curative intent, prior laser photoresection, and/or concurrent external radiation. Survival was the strongest predictor of the reaction. Radiation bronchitis and stenosis is a new clinical entity that must be identified in bronchial brachytherapy patients and treated appropriately. 23 refs., 3 figs., 7 tabs.« less

Safety and immunogenicity of different doses and schedules of a live attenuated tetravalent dengue vaccine (TDV) in healthy adults: A Phase 1b randomized study.

PubMed

Rupp, Richard; Luckasen, Gary Joseph; Kirstein, Judith Lee; Osorio, Jorge E; Santangelo, Joseph D; Raanan, Marsha; Smith, Mary Kathryn; Wallace, Derek; Gordon, Gilad S; Stinchcomb, Dan T

2015-11-17

A safe, effective dengue vaccine that can simultaneously induce immunity to all four dengue virus serotypes (DENV-1-4) is a public health priority. A chimeric tetravalent dengue vaccine (TDV) based on an attenuated DENV-2 serotype backbone was evaluated in healthy, flavivirus-seronegative adults. In this randomized, multicenter, Phase 1b study conducted in the United States, the safety and immunogenicity of TDV were evaluated in 140 participants aged 18-45 years in six dosing regimen study groups. Participants were injected subcutaneously on Days 0 and 90; placebo (saline) was injected where appropriate to maintain double blinding. Three different TDV dosages (TDV, a vaccine in which TDV-4 had been increased three-fold, and a one-tenth TDV dose), and single or double dosing were evaluated in one and/or both arms. Primary endpoints were solicited and unsolicited adverse events (AEs) and seroconversion rates to DENV-1-4 at Day 120. The severity of all AEs was generally mild. The most common unsolicited AEs were headache (52%), fatigue (43%) and myalgia (29%). The incidence of injection site pain ranged from 29 to 64% and 5 to 52% among study groups after the first and second doses, respectively. At Day 120, the ranges of seroconversion rates among the groups were DEN-1: 84-100%; DEN-2: 96-100%; DEN-3: 83-100%; and DEN-4: 33-77%. More than 80% of participants in each group seroconverted to at least three dengue serotypes. Substantial GMT increases from baseline were observed for DEN-1-3 at all time points from Day 30 onward; DEN-4 GMT increases were lower. Increasing TDV-4 slightly increased DEN-4 GMT, did not impact DEN-2 and DEN-3 GMT, but reduced DEN-1 GMT. Neither multiple dosing in both arms, nor one-tenth TDV dosing meaningfully impacted GMT increases relative to TDV. All TDV doses and dosing schedules were well tolerated and immunogenic in healthy flavivirus-naive adults (ClinicalTrials.gov NCT01511250). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers.

PubMed Central

McClelland, G R; Cooper, S M; Pilgrim, A J

1990-01-01

1. Twelve healthy male volunteers participated in four experimental occasions during each of which they were dosed with one of the following anti-psychotic drugs: chlorpromazine (50 mg), haloperidol (3 mg), sulpiride (400 mg) and placebo. Drugs were allocated to subjects in a double-blind, crossover fashion. 2. The subject's mood state, psychometric performance and electroencephalogram (EEG) were assessed pre-dose, and at 2, 4, 6, 8, 24 and 48 h post-dose. Mood states were assessed using 16 visual analogue scales and psychomotor performance was measured using the following tests: elapsed time estimation, tapping rate, choice reaction times, a rapid information processing task, flash fusion threshold, a manipulative motor task, digit span, body sway and tremor. 3. Chlorpromazine and haloperidol significantly reduced subjective ratings of 'alertness' and 'contentedness', and haloperidol significantly reduced feelings of 'calmness'. Sulpiride did not significantly affect any of the visual analogue scales. 4. All three anti-psychotic drugs had similar EEG effects with peak effect 2 to 4 h postdose. The profile was characterised by an increase in the proportion of slow wave activity (delta and theta) as well as decreased alpha (8-14 Hz) and faster (beta) wave activity. 5. Chlorpromazine reduced tapping rate and increased choice reaction movement times. Haloperidol reduced the flash fusion threshold frequency at 6 h post-dose. Sulpiride prolonged the duration of the manipulative motor task, particularly at 48 h post-dose. 6. All three anti-psychotic drugs impaired performance on the rapid information processing task. Chlorpromazine significantly reduced the number of correct letter pair identifications at 2, 4 and 6 h post-dose, haloperidol at 4, 6, 8, 24 and 48 h post-dose, and sulpiride at 24 h post-dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2288826

Geographical diffusion of prazosin across Veterans Health Administration: Examination of regional variation in daily dosing and quality indicators among veterans with posttraumatic stress disorder.

PubMed

Abrams, Thad E; Lund, Brian C; Alexander, Bruce; Bernardy, Nancy C; Friedman, Matthew J

2015-01-01

Posttraumatic stress disorder (PTSD) is a high-priority treatment area for the Veterans Health Administration (VHA), and dissemination patterns of innovative, efficacious therapies can inform areas for potential improvement of diffusion efforts and quality prescribing. In this study, we replicated a prior examination of the period prevalence of prazosin use as a function of distance from Puget Sound, Washington, where prazosin was first tested as an effective treatment for PTSD and where prazosin use was previously shown to be much greater than in other parts of the United States. We tested the following three hypotheses related to prazosin geographic diffusion: (1) a positive geographical correlation exists between the distance from Puget Sound and the proportion of users treated according to a guideline recommended minimum therapeutic target dose (>/=6 mg/d), (2) an inverse geographic correlation exists between prazosin and benzodiazepine use, and (3) no geographical correlation exists between prazosin use and serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) use. Among a national sample of veterans with PTSD, overall prazosin utilization increased from 5.5 to 14.8% from 2006 to 2012. During this time period, rates at the Puget Sound VHA location declined from 34.4 to 29.9%, whereas utilization rates at locations a minimum of 2,500 miles away increased from 3.0 to 12.8%. Rates of minimum target dosing fell from 42.6 to 34.6% at the Puget Sound location. In contrast, at distances of at least 2,500 miles from Puget Sound, minimum threshold dosing rates remained stable (range, 18.6 to 17.7%). No discernible association was demonstrated between SSRI/SNRI or benzodiazepine utilization and the geographic distance from Puget Sound. Minimal threshold dosing of prazosin correlated positively with increased diffusion of prazosin use, but there was still a distance diffusion gradient. Although prazosin adoption has improved, geographic differences persist in both prescribing rates and minimum target dosing. Importantly, these regional disparities appear to be limited to prazosin prescribing and are not meaningfully correlated with SSRI/SNRI and benzodiazepine use as indicators of PTSD prescribing quality.

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

PubMed

Rush, C R; Baker, R W; Rowlett, J K

2000-02-01

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5-15.0 mg), triazolam (0.0625-0.3750 mg), pentobarbital (25-150 mg), caffeine (100-600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines.

The effects of oxytocin and atosiban on the modulation of heart rate in pregnant women.

PubMed

Weissman, Amir; Tobia, Rana Swed; Burke, Yechiel Z; Maxymovski, Olga; Drugan, Arie

2017-02-01

To evaluate autonomic modulation of heart rate in pregnant women treated with oxytocin to induce labor and with atosiban (an oxytocin antagonist) to arrest preterm labor. A prospective study with two cohorts: 14 pregnant women treated with atosiban for premature uterine contractions, and 28 women undergoing induction of labor with oxytocin. Computerized analyses of the electrocardiogram were performed with spectral and nonlinear dynamic analyses. Atosiban did not alter any of the variables associated with heart rate variability, whereas oxytocin showed a dose-dependent decrease in heart rate (p < 0.05) and a significant increase in all spectral variables studied (p < 0.01). Atosiban has no adverse effects on the cardiovascular system or the modulation of heart rate. Oxytocin, on the other hand, can cause a dose-dependent bradycardic effect and an increase in the spectral power, thus should be used with caution in certain pregnant women.

Leukemia, lymphoma and multiple myeloma mortality (1950–1999) and incidence (1969–1999) in the Eldorado uranium workers cohort

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

Zablotska, Lydia B., E-mail: Lydia.Zablotska@ucsf.edu; Lane, Rachel S.D.; Frost, Stanley E.

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months andmore » the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. - Highlights: • We analyzed long-term follow-up for hematologic cancers of the Eldorado uranium workers. • Workers were exposed to a unique combination of radon decay products (RDP) and gamma (γ) ray doses. • Exposures to RDP and γ-ray doses were not associated with significantly increased risks of cancers. • Radiation risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma were increased. • Study findings provide additional support for radiation-related risks of CLL.« less

Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator

PubMed Central

Mortazavi, SMJ; Mosleh-Shirazi, MA; Tavassoli, AR; Taheri, M; Mehdizadeh, AR; Namazi, SAS; Jamali, A; Ghalandari, R; Bonyadi, S; Haghani, M; Shafie, M

2013-01-01

The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1st group received microwave exposure. The 2nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response. PMID:23930107

Effect of injected rotenone on the production and composition of urine from the rainbow trout (Salmo gairdneri)

USGS Publications Warehouse

Erickson, D.A.; Gingerich, W.H.

1986-01-01

Renal function was evaluated in adult rainbow trout (Salmo gairdneri) dosed i.a. with rotenone at 225 and 275 μg/kg. The chemical composition of urine samples and urine flow rates collected over a 5-h pretreatment period were compared with hourly urine samples collected over a 5-h posttreatment period. Significant increases in osmolality and in concentrations of sodium, potassium, chloride, glucose, and total protein were observed in the urine of treated fish. Urine solute concentrations reached maximum values within 1 to 3 h after treatment and decreased thereafter, indicating that the effects were reversible. Concentrations of sodium and chloride were highly correlated in 2-h posttreatment urine samples at the low (r = 0.922) and high (r = 0.981) rotenone treatments. Urine flow rates were reduced in trout at each dose of rotenone but the decrease in volume of urine voided was not dose-dependent. In a separate study, [14C]polyethylene glycol was used as a filtration marker to determine the effect of rotenone treatment (225 &mu:g/kg) on urine flow rate, glomerular filtration rate, and renal water reabsorption. We showed that posttreatment urine flow rates were reduced partly by reduced glomerular filtration and partly by increased water reabsorption. Transient increases in plasma osmolality and hematocrit also were observed 0.5 h after rotenone treatment.

Moving Beyond Maximum Tolerated Dose for Targeted Oncology Drugs: Use of Clinical Utility Index to Optimize Venetoclax Dosage in Multiple Myeloma Patients.

PubMed

Freise, K J; Jones, A K; Verdugo, M E; Menon, R M; Maciag, P C; Salem, A H

2017-12-01

Exposure-response analyses of venetoclax in combination with bortezomib and dexamethasone in previously treated patients with multiple myeloma (MM) were performed on a phase Ib venetoclax dose-ranging study. Logistic regression models were utilized to determine relationships, identify subpopulations with different responses, and optimize the venetoclax dosage that balanced both efficacy and safety. Bortezomib refractory status and number of prior treatments were identified to impact the efficacy response to venetoclax treatment. Higher venetoclax exposures were estimated to increase the probability of achieving a very good partial response (VGPR) or better through venetoclax doses of 1,200 mg. However, the probability of neutropenia (grade ≥3) was estimated to increase at doses >800 mg. Using a clinical utility index, a venetoclax dosage of 800 mg daily was selected to optimally balance the VGPR or better rates and neutropenia rates in MM patients administered 1-3 prior lines of therapy and nonrefractory to bortezomib. © 2017 American Society for Clinical Pharmacology and Therapeutics.

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.

SU-F-T-274: Modified Dose Calibration Methods for IMRT QA

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

Luo, W; Westlund, S

2016-06-15

Purpose: To investigate IMRT QA uncertainties caused by dose calibration and modify widely used dose calibration procedures to improve IMRT QA accuracy and passing rate. Methods: IMRT QA dose measurement is calibrated using a calibration factor (CF) that is the ratio between measured value and expected value corresponding to the reference fields delivered on a phantom. Two IMRT QA phantoms were used for this study: a 30×30×30 cm3 solid water cube phantom (Cube), and the PTW Octavius phantom. CF was obtained by delivering 100 MUs to the phantoms with different reference fields ranging from 3×3 cm2 to 20×20 cm{sup 2}.more » For Cube, CFs were obtained using the following beam arrangements: 2-AP Field - chamber at dmax, 2-AP Field - chamber at isocenter, 4-beam box - chamber at isocenter, and 8 equally spaced fields and chamber at isocenter. The same plans were delivered on Octavius and CFs were derived for the dose at the isocenter using the above beam arrangements. The Octavius plans were evaluated with PTW-VeriSoft (Gamma criteria of 3%/3mm). Results: Four head and neck IMRT plans were included in this study. For point dose measurement with Cube, the CFs with 4-Field gave the best agreement between measurement and calculation within 4% for large field plans. All the measurement results agreed within 2% for a small field plan. Compared with calibration field sizes, 5×5 to 15×15 were more accurate than other field sizes. For Octavius, 4-Field calibration increased passing rate by up to 10% compared to AP calibration. Passing rate also increased by up to 4% with the increase of field size from 3×3 to 20×20. Conclusion: IMRT QA results are correlated with calibration methods used. The dose calibration using 4-beam box with field sizes from 5×5 to 20×20 can improve IMRT QA accuracy and passing rate.« less

Radiotherapy of soft tissue sarcomas in dogs.

PubMed

McChesney, S L; Withrow, S J; Gillette, E L; Powers, B E; Dewhirst, M W

1989-01-01

Megavoltage radiotherapy was administered to 42 dogs with soft tissue sarcoma. Acceptable local control of these aggressive tumors was achieved after one year of treatment. Control rates of 48 and 67% were obtained at doses of 45 and 50 gray (Gy), respectively. At 2 years, control rates decreased to 33% at the dose of 50 Gy. Serious complications developed in 4 of 42 dogs at doses of 40 to 50 Gy. The estimated dose with a 50% probability for causing serious complications was 54 Gy, given in 10 fractions. We believe that the large doses per fraction used in this study probably led to an increased probability for necrosis. Hemangiopericytomas seemed to be more responsive than fibrosarcomas. Only 2 of 11 recurrent tumors were controlled with surgery. Good local control was achieved with radiation alone for one year at doses with a low probability for serious complications; however, higher total radiation doses or combined modalities, such as surgery and radiation or radiation and hyperthermia, may be needed for longer-term control.

A system for electron therapy dosimetry surveys with thermoluminescence dosimeters.

PubMed

Soares, C G; Ehrlich, M; Padikal, T N; Gromadzki, Z C

1982-11-01

Radiation-therapy dosimetry surveys employing thermoluminescence dosimeters (TLDs) are now being considered for high-energy electron beams. Using a system of individually calibrated pressed LiF TLDs in a water and a polystyrene phantom, we established that the distortions of depth-dose distributions in non-conducting materials previously observed at high absorbed doses and high dose rates were not detectable in the present geometry at doses and dose rates as much as 40 times higher than those employed in radiation therapy. The system was then used to measure TLD response in water and in polystyrene in the nominal electron-energy range from 7 to 18 MeV. In the water phantom, the well-known trend for TLD response to decrease with increasing electron energy was observed. In the polystyrene phantom, TLD response was found to be independent of electron energy.

Effect of low-dose scopolamine on autonomic control of the heart

NASA Technical Reports Server (NTRS)

Raeder, E. A.; Stys, A.; Cohen, R. J.

1997-01-01

Background: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. Methods: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. Results: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. Conclusions: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

Update to Millstone 3 elevated pH tests

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

Bergmann, C.A.; Perock, J.D.; Hudson, M.J.B.

1995-03-01

In view of the potential radiological benefits of elevated coolant pH operation, Northwest Utilities (NU), in support of an EPRI-Westinghouse program, agreed to operate the Millstone 3 plant at the start of its second fuel cycle as a demonstration of the effect of elevated coolant pH on out-of-core radiation fields. Operating with an elevated pH is defined as operating with an average lithium concentration of 3.35 ppm, until reaching an end of cycle pH of 7.2 or 7.4. The plant operated during its second and third cycles with an elevated coolant pH. The end of cycle pH during the secondmore » cycle was 7.4, and 7.2 during the third cycle. (During the first cycle, operation was with a coordinated pH of 7.0). Evaluation of the dose rate trends in Millstone 3 after two cycles of elevated coolant pH operation concluded that an elevated coolant pH resulted in a 15 percent lower component dose rate compared to other plants that operated with coordinated pH 6.9. However, due to a possible increase in fuel clad corrosion, operation during cycle 4 was restricted to pH 6.9 coordinated chemistry, with the exception of the last two months during which the pH increased to 7.35. At the end of cycle 4 (EOC4), there was a greater increase in component and crud trap dose rates than expected. This paper reviews the radiological trends in the plant and discusses the potential causes for the increase in the dose rates at EOC4.« less

Studies on color-center formation in glass utilizing measurements made during 1 to 3 MeV electron irradiation

NASA Technical Reports Server (NTRS)

Swyler, K. J.; Levy, P. W.

1976-01-01

The coloring of NBS 710 glass was studied using a facility for making optical absorption measurements during and after electron irradiation. The induced absorption contains three Gaussian shaped bands. The color center growth curves contain two saturating exponential and one linear components. After irradiation the coloring decays can be described by three decreasing exponentials. At room temperature both the coloring curve plateau and coloring rate increases with increasing dose rate. Coloring measurements made at fixed dose rate but at increasing temperature indicate: (1) The coloring curve plateau decreases with increasing temperature and coloring is barely measurable near 400 C. (2) The plateau is reached more rapidly as the temperature increases. (3) The decay occurring after irradiation cannot be described by Arrhenius kinetics. At each temperature the coloring can be explained by simple kinetics. The temperature dependence of the decay can be explained if it is assumed that the thermal untrapping is controlled by a distribution of activation energies.

Regional peripheral and CNS hemodynamic effects of intrathecal administration of a substance P receptor agonist.

PubMed

Helke, C J; Phillips, E T; O'Neill, J T

1987-11-01

Regional CNS and peripheral hemodynamic effects of the intrathecal (i.t.) administration of a substance P receptor agonist, [pGlu5,MePhe8,MeGly9]-substance P5-11 ([DiMe]-SP), were studied in anesthetized rats with the radioactive microsphere technique. It was previously shown that [DiMe]-SP caused a sympathetically mediated increase in mean arterial pressure (MAP) by an action within the spinal cord. In this study, [DiMe]-SP (5 and 33 nmol, i.t.) increased MAP. The 5 nmol dose increased resistance in cutaneous, renal, splanchnic, and adrenal vascular beds but decreased resistance, and increased blood flow in some skeletal muscle beds. Total peripheral resistance was unchanged. The 33 nmol dose increased resistance in each peripheral vascular bed analyzed and increased total peripheral resistance. Whereas each dose increased heart rate, stroke volume and cardiac output were unchanged with the 5 nmol dose and were reduced with the 33 nmol dose. Neither dose of [DiMe]-SP significantly altered regional brain or spinal cord blood flows. These data show that the i.t. administration of the SP agonist, [DiMe]-SP, increased vascular tone to most peripheral vascular beds whereas the low dose caused a vasodilation of skeletal muscle. These effects are consistent with the notion of a dose-related activation of SP receptors in the spinal cord affecting sympathetic outflow to the adrenals and to the vasculature.

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.

Mesalamine Dose Escalation Reduces Fecal Calprotectin In Patients With Quiescent Ulcerative Colitis

PubMed Central

Osterman, Mark T.; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D.

2014-01-01

Background & Aims Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized, controlled trial to investigate whether increasing doses mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n=26) or a group that increased its dose by 2.4 g/day for 6 weeks (n=26). The primary outcome was continued remission with FC<50 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/g (among patients with pre-randomization values above these levels). Results The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P=.0496). More patients in the dose escalation group reduced FC to below 100 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov: NCT00652145 PMID:24793028

Biphasic and monophasic repair: comparative implications for biologically equivalent dose calculations in pulsed dose rate brachytherapy of cervical carcinoma

PubMed Central

Millar, W T; Davidson, S E

2013-01-01

Objective: To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma. Methods: Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength. Results: When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/β ratios as a consequence of the described concept of extended equivalence. Conclusion: The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed. Advances in knowledge: Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/β ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma. PMID:23934965

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

Brown, P.H.; Krishnamurthy, G.T.; Bobba, V.R.

The radiation absorbed doses from five commercially available hepatobiliary agents-Tc-99m-tagged analogs of IDA (EIDA, PIPIDA, HIDA, PBIDA, DISIDA*) have been calculated from biokinetic data in 41 normal subjects. Serial gamma images, with blood and urine samples, were obtained to calculate cumulated radioactivity in the source organs: blood, kidey, bladder, liver, gallbladder, and intestines. The critical organ was the gallbladder, with an absorbed-dose range of 690 to 780 mrad/mCi. Absorbed doses for other target organs were: upper large intestine 320 to 370 mrad/mCi, lower large intestine 210 to 240, small intestine 170 to 200, liver 65 (DISIDA) to 130 (PBIDA), ovariesmore » 63 to 72, and urinary bladder wall 23 (PBIDA) to 36 (EIDA). The radiation absorbed dose was largely independent of changes in chemical structure except in (a) the liver, where absorbed dose varied by a factor of two in proportion to the rate of excretion of the IDA agent from the liver, and (b) the urinary bladder, where absorbed dose varied by a factor of 1.6 because of differences in rate of excretion. When the stimulus for gallbladder emptying is changed from whole-meal ingestion to cholecystokinin injection, the absorbed dose to the gallbladder increases to approx. 1 rad/mCi; if no gallbladder emptying is assumed, its absorbed dose increases to approx. 1.9 rad/mCi. In the absence of contraindication, the gallbladder absorbed dose may thus be decreased by inducing gallbladder emptying at the end of the imaging study.« less

Lung Cancer Mortality (1950–1999) among Eldorado Uranium Workers: A Comparison of Models of Carcinogenesis and Empirical Excess Risk Models

PubMed Central

Eidemüller, Markus; Jacob, Peter; Lane, Rachel S. D.; Frost, Stanley E.; Zablotska, Lydia B.

2012-01-01

Lung cancer mortality after exposure to radon decay products (RDP) among 16,236 male Eldorado uranium workers was analyzed. Male workers from the Beaverlodge and Port Radium uranium mines and the Port Hope radium and uranium refinery and processing facility who were first employed between 1932 and 1980 were followed up from 1950 to 1999. A total of 618 lung cancer deaths were observed. The analysis compared the results of the biologically-based two-stage clonal expansion (TSCE) model to the empirical excess risk model. The spontaneous clonal expansion rate of pre-malignant cells was reduced at older ages under the assumptions of the TSCE model. Exposure to RDP was associated with increase in the clonal expansion rate during exposure but not afterwards. The increase was stronger for lower exposure rates. A radiation-induced bystander effect could be a possible explanation for such an exposure response. Results on excess risks were compared to a linear dose-response parametric excess risk model with attained age, time since exposure and dose rate as effect modifiers. In all models the excess relative risk decreased with increasing attained age, increasing time since exposure and increasing exposure rate. Large model uncertainties were found in particular for small exposure rates. PMID:22936975

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

Risk of ischemic heart disease in women after radiotherapy for breast cancer.

PubMed

Darby, Sarah C; Ewertz, Marianne; McGale, Paul; Bennet, Anna M; Blom-Goldman, Ulla; Brønnum, Dorthe; Correa, Candace; Cutter, David; Gagliardi, Giovanna; Gigante, Bruna; Jensen, Maj-Britt; Nisbet, Andrew; Peto, Richard; Rahimi, Kazem; Taylor, Carolyn; Hall, Per

2013-03-14

Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).

Development of a technique and conceptual design of a survey instrument for beta dosimetry in the nuclear power industry

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

Murphy, R.O.

1986-01-01

Before an employee of the nuclear power industry can be assigned to work in an area with radiation hazards, the total dose rate from all radiation present should be known to determine the risk. As the plants age, the level of maintenance has increased and certain tasks have required the workers to be exposed to intense beta radiation fields. Currently available survey instruments do not accurately assess the beta dose or dose rate in many circumstances due to several factors, including the fluctuation of the response of the detector due to the variation in the energy of the beta particlesmore » comprising the radiation field. This research involved developing a technique for calculating the beta dose rate, using the differential energy spectrum and the fluence rate for the beta particles, the fundamental features of the beta radiation. The energy spectrum was used to determine a spectrum weighted average mass stopping power (SWAMPS). The SWAMPS, when multiplied by the fluence rate, gives the energy deposited per unit mass per second, which is the absorbed dose rate for the beta radiation. Reference sources were developed and calibrated using an extrapolation chamber that had, itself, been calibrated using beta sources at the National Bureau of Standards. Different spectrometry systems were tested for applicability to the SWAMPS technique.« less

Detection of pulmonary nodule growth with dose reduced chest tomosynthesis: a human observer study using simulated nodules

NASA Astrophysics Data System (ADS)

Söderman, Christina; Johnsson, Ã. se; Vikgren, Jenny; Rossi Norrlund, Rauni; Molnar, David; Mirzai, Maral; Svalkvist, Angelica; Mânsson, Lars Gunnar; Bâth, Magnus

2016-03-01

Chest tomosynthesis may be a suitable alternative to computed tomography for the clinical task of follow up of pulmonary nodules. The aim of the present study was to investigate the detection of pulmonary nodule growth suggestive of malignancy using chest tomosynthesis. Previous studies have indicated remained levels of detection of pulmonary nodules at dose levels corresponding to that of a conventional lateral radiograph, approximately 0.04 mSv, which motivated to perform the present study this dose level. Pairs of chest tomosynthesis image sets, where the image sets in each pair were acquired of the same patient at two separate occasions, were included in the study. Simulated nodules with original diameters of approximately 8 mm were inserted in the pairs of image sets, simulating situations where the nodule had remained stable in size or increased isotropically in size between the two different imaging occasions. Four different categories of nodule growth were included, corresponding to a volume increase of approximately 21 %, 68 %, 108 % and 250 %. All nodules were centered in the depth direction in the tomosynthesis images. All images were subjected to a simulated dose reduction, resulting in images corresponding to an effective dose of 0.04 mSv. Four observers were given the task of rating their confidence that the nodule was stable in size or not on a five-level rating scale. This was done both before any size measurements were made of the nodule as well as after measurements were performed. Using Receiver operating characteristic analysis, the rating data for the nodules that were stable in size was compared to the rating data for the nodules simulated to have increased in size. Statistically significant differences between the rating distributions for the stable nodules and all of the four nodule growth categories were found. For the three largest nodule growths, nearly perfect detection of nodule growth was seen. In conclusion, the present study indicates that during optimal imaging conditions and for nodules with diameters of approximately 8 mm that grow fairly symmetrically, chest tomosynthesis performed at a dose level corresponding to that of a lateral chest radiograph can, with high sensitivity, differentiate nodules stable in size from nodules growing at rates associated with fast growing malignant nodules.

Preoperative steroid administration: effect on morbidity among patients undergoing intestinal bowel resection for Crohńs disease.

PubMed

Bruewer, Matthias; Utech, Markus; Rijcken, Emile J M; Anthoni, Christoph; Laukoetter, Mike G; Kersting, Sabine; Senninger, Norbert; Krieglstein, Christian F

2003-12-01

Long-term steroid therapy may predispose to increased perioperative morbidity in patients undergoing surgery with bowel anastomoses. The aim of our study was to review our data to determine if the steroid dosage is associated with the incidence of early complications after bowel resection in patients with prolonged steroid therapy for Crohńs disease (CD). Altogether, 397 patients underwent bowel resection with primary intestinal anastomoses for CD between 1982 and 2000 in our institution. The mortality and morbidity rates, anastomotic leakage, wound infections, intraabdominal abscesses, reoperation rate, and length of postoperative hospitalization in patients who were having high-dose (>/= 20 mg of prednisolone per day, n = 73) and low-dose (< 20 mg prednisolone per day, n = 146) steroid therapy for more than 1 month before surgery were compared with those of patients ( n = 177) who were not receiving steroids. Statistical analysis was performed using Fisher's exact test and Student's t-test, with p < 0.05 considered significant. The three groups were similar in terms of gender, duration since first diagnosis, American Society of Anesthesiologists classification, and obesity. Mortality, morbidity, anastomotic leakage, wound infections, intraabdominal abscesses, reoperation rate, and average postoperative stay were not statistically different in patients with high-dose, low-dose, or no steroid therapy. The only factor associated with increased morbidity was a low preoperative hemoglobin level. Our results demonstrate that, in patients who are undergoing bowel resection for CD, even high-dose prolonged preoperative systemic steroid therapy is not associated with increased postoperative complications.

Characterization of Thymol blue Radiochromic dosimeters for high dose applications

NASA Astrophysics Data System (ADS)

Aldweri, Feras M.; Abuzayed, Manar H.; Al-Ajaleen, Musab S.; Rabaeh, Khalid A.

2018-03-01

Thymol blue (TB) solutions and Thymol blue Polyvinyl Alcohol (TB-PVA) films have been introduced as Radiochromic dosimeter for high dose applications. The dosimeters were irradiated with gamma ray (60Co source) from 5 to 30 kGy for film, and from 0.150 kGy to 4 kGy for solution. The optical density of unirradiated and irradiated TB solution as well as TB-PVA film dosimeters were studied in terms of absorbance at 434 nm using UV/VIS spectrophotometer. The effects of scan temperature, light pre-gamma irradiation, dose rate, relative humidity and stability of the absorbance of solutions and films after irradiation were investigated. We found the dose sensitivity of TB solution and TB-PVA film dosimeters increases significantly with increases of the absorbed dose as well as with the increases of TB dye concentrations. The useful dose range of developed TB solutions and TB-PVA films dosimeters is in the range 0.125-1 kGy and of 5-20 kGy, respectively.

Stomatal and non-stomatal factors regulated the photosynthesis of soybean seedlings in the present of exogenous bisphenol A.

PubMed

Jiao, Liya; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2017-11-01

Bisphenol A (BPA) is an emerging environmental endocrine disruptor that has toxic effects on plants growth. Photosynthesis supplies the substances and energy required for plant growth, and regulated by stomatal and non-stomatal factors. Therefore, in this study, to reveal how BPA affects photosynthesis in soybean seedlings (Glycine max L.) from the perspective of stomatal and non-stomatal factors, the stomatal factors (stomatal conductance and behaviours) and non-stomatal factors (Hill reaction, apparent quantum efficiency, Rubisco activity, carboxylation efficiency, the maximum Rubisco carboxylation velocity, ribulose-1,5-bisphospate regeneration capacities mediated by maximum electron transport rates, and triose phosphate utilization rate) were investigated using a portable photosynthesis system. Moreover, the pollution of BPA in the environment was simulated. The results indicate that low-dose BPA enhanced net photosynthetic rate (P n ) primarily by promoting stomatal factors, resulting in increased relative growth rates and accelerated soybean seedling growth. High-dose BPA decreases the P n by simultaneously inhibiting stomatal and non-stomatal factors, and this inhibition decreases the relative growth rates further reducing soybean seedling growth. Following the withdrawal of BPA, all of the indices were restored to varying degrees. In conclusion, low-dose BPA increased the P n by promoting stomatal factors while high-dose BPA decreased the P n by simultaneously inhibiting stomatal and non-stomatal factors. These findings provide a model (or, hypothesis) for the effects of BPA on plant photosynthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Hydrocortisone at stress-associated concentrations helps maintain human heart rate variability during subsequent endotoxin challenge.

PubMed

Rassias, Athos J; Guyre, Paul M; Yeager, Mark P

2011-12-01

We evaluated the differential impact of stress-associated vs high pharmacologic concentrations of hydrocortisone pretreatment on heart rate variability (HRV) during a subsequent systemic inflammatory stimulus. Healthy volunteers were randomized to receive placebo (Control) and hydrocortisone at 1.5 μg/kg per minute (STRESS) or at 3.0 μg/kg per minute (PHARM) as a 6-hour infusion. The STRESS dose was chosen to replicate the condition of physiologic adrenal cortical output during acute systemic stress. The PHARM dose was chosen to induce a supraphysiologic concentration of cortisol. The next day, all subjects received 2 ng/kg Escherichia coli endotoxin (lipopolysaccharide). Heart rate variability was analyzed with the statistic approximate entropy (ApEn). A lower ApEn correlates with decreased HRV. At the 3-hour nadir, the decrease in ApEn in the STRESS group was significantly less compared to placebo (P < .03), whereas ApEn in the PHARM group was not statistically different. We also found that the maximal decrease in ApEn preceded maximal increase in heart rate in all groups. The decrease in R-R interval was maximal at 4 hours, whereas the ApEn nadir was 1 hour earlier at 3 hours. Pretreatment with a stress dose of hydrocortisone but not a higher pharmacologic dose maintained a significantly higher ApEn after endotoxin exposure when compared to a placebo. In addition, decreases in ApEn preceded increases in heart rate. Copyright © 2011 Elsevier Inc. All rights reserved.

A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

PubMed

Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

2014-03-01

The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Survey of distribution of seasonal influenza vaccine doses in 201 countries (2004-2015): The 2003 World Health Assembly resolution on seasonal influenza vaccination coverage and the 2009 influenza pandemic have had very little impact on improving influenza control and pandemic preparedness.

PubMed

Palache, A; Abelin, A; Hollingsworth, R; Cracknell, W; Jacobs, C; Tsai, T; Barbosa, P

2017-08-24

There is no global monitoring system for influenza vaccination coverage, making it difficult to assess progress towards the 2003 World Health Assembly (WHA) vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply International Task Force (IVS) developed a survey method to assess the global distribution of influenza vaccine doses as a proxy for vaccination coverage rates. The latest dose distribution data for 2014 and 2015 was used to update previous analyses. Data were confidentially collected and aggregated by the IFPMA Secretariat, and combined with previous IFPMA IVS survey data (2004-2013). Data were available from 201 countries over the 2004-2015 period. A "hurdle" rate was defined as the number of doses required to reach 15.9% of the population in 2008. Overall, the number of distributed doses progressively increased between 2004 and 2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses were distributed in 2015 than in 2011. Twenty-three countries were above the hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted for about 95% of doses distributed. But in EURO and WPRO, distribution rates in 2015 were only marginally higher than in 2004, and in EURO there was an overall downward trend in dose distribution. The vast majority of countries cannot meet the 2003WHA coverage targets and are inadequately prepared for a global influenza pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the world's population, there is urgency to redress the gross inequities in disease prevention and in pandemic preparedness. The 2003WHA resolution must be reviewed and revised and a call issued for the renewed commitment of Member States to influenza vaccination coverage targets. Copyright © 2017. Published by Elsevier Ltd.

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.

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.

Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside.

PubMed Central

Jaski, B E; Fifer, M A; Wright, R F; Braunwald, E; Colucci, W S

1985-01-01

Milrinone is a potent positive inotropic and vascular smooth muscle-relaxing agent in vitro, and therefore, it is not known to what extent each of these actions contributes to the drug's hemodynamic effects in patients with heart failure. In 11 patients with New York Heart Association class III or IV congestive heart failure, incremental intravenous doses of milrinone were administered to determine the dose-response relationships for heart rate, systemic vascular resistance, and inotropic state, the latter measured by peak positive left ventricular derivative of pressure with respect to time (dP/dt). To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload. Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner. At the two lowest milrinone doses resulting in serum concentrations of 63 +/- 4 and 156 +/- 5 ng/ml, respectively, milrinone caused significant increases in stroke volume and dP/dt, but no changes in systemic vascular resistance or heart rate. At the maximum milrinone dose administered (mean serum concentration, 427 +/- 11 ng/ml), heart rate increased from 92 +/- 4 to 99 +/- 4 bpm (P less than 0.01), mean aortic pressure fell from 82 +/- 3 to 71 +/- 3 mmHg (P less than 0.01), right atrial pressure fell from 15 +/- 2 to 7 +/- 1 mmHg (P less than 0.005), left ventricular end-diastolic pressure fell from 26 +/- 3 to 18 +/- 3 (P less than 0.005), stroke volume index increased from 20 +/- 2 to 30 +/- 2 ml/m2 (P less than 0.005), stroke work index increased from 14 +/- 2 to 21 +/- 2 g X m/m2 (P less than 0.01), and dP/dt increased from 858 +/- 54 to 1,130 +/- 108 mmHg/s (P less than 0.005). When compared with nitroprusside for a matched reduction in mean aortic pressure or systemic vascular resistance, milrinone caused a significantly greater increase in stroke work index at the same or lower left ventricular end-diastolic pressure. Milrinone caused a concentration-related increase in dP/dt (32% increase at maximum milrinone dose), whereas nitroprusside had no effect. These data in patients with severe heart failure indicate that in addition to a vasodilating effect, milrinone exerts a concentration-related positive inotropic action that contributes significantly to the drug's overall hemodynamic effects. The positive inotropic action occurs at drug levels that do not exert significant chronotropic or vasodilator effects. Images PMID:3973022

Environmental standards for ionizing radiation: theoretical basis for dose-response curves.

PubMed Central

Upton, A C

1983-01-01

The types of injury attributable to ionizing radiation are subdivided, for purposes of risk assessment and radiological protection, into two broad categories: stochastic effects and nonstochastic effects. Stochastic effects are viewed as probablistic phenomena, varying in frequency but not severity as a function of the dose, without any threshold; nonstochastic effects are viewed as deterministic phenomena, varying in both frequency and severity as a function of the dose, with clinical thresholds. Included among stochastic effects are heritable effects (mutations and chromosome aberrations) and carcinogenic effects. Both types of effects are envisioned as unicellular phenomena which can result from nonlethal injury of individual cells, without the necessity of damage to other cells. For the induction of mutations and chromosome aberrations in the low-to-intermediate dose range, the dose-response curve with high-linear energy transfer (LET) radiation generally conforms to a linear nonthreshold relationship and varies relatively little with the dose rate. In contrast, the curve with low-LET radiation generally conforms to a linear-quadratic relationship, rising less steeply than the curve with high-LET radiation and increasing in slope with increasing dose and dose rate. The dose-response curve for carcinogenic effects varies widely from one type of neoplasm to another in the intermediate-to-high dose range, in part because of differences in the way large doses of radiation can affect the promotion and progression of different neoplasms. Information about dose-response relations for low-level irradiation is fragmentary but consistent, in general, with the hypothesis that the neoplastic transformation may result from mutation, chromosome aberration or genetic recombination in a single susceptible cell. PMID:6653536

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.

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.

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

Ghosh, Swarajit N., E-mail: snghosh@mcw.ed; Zhang Rong; Department of Pharmacology, Harbin Medical University College of Pharmacy, Harbin

Purpose: To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy). Methods and Materials: Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death. Results: Survival after amore » dose of 10 Gy to the thorax was not different from that of unirradiated rats for <=1 year. Survival decreased to <50% by 45 weeks after 12 Gy and by 8-9 weeks after 15 Gy. Captopril (17-56mg/kg/d) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity, and histopathologic evidence of injury. Radiation-induced increases in the breathing rate were prevented even if captopril was started 1 week after irradiation or if it was discontinued after 5 weeks. Losartan, although effective in reducing mortality, was not as efficacious as captopril in mitigating radiation-induced increases in the breathing rate or altered vasoreactivity. Conclusion: In rats, a moderate thoracic radiation dose induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was begun 1 week after radiation or if discontinued 5 weeks after exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea.« less

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.

The thermoregulatory mechanism of melatonin-induced hypothermia in chicken.

PubMed

Rozenboim, I; Miara, L; Wolfenson, D

1998-01-01

The involvement of melatonin (Mel) in body temperature (Tb) regulation was studied in White Leghorn layers. In experiment 1, 35 hens were injected intraperitoneally with seven doses of Mel (0, 5, 10, 20, 40, 80, or 160 mg Mel/kg body wt) dissolved in ethanol. Within 1 h, Mel had caused a dose-dependent reduction in Tb. To eliminate a possible vehicle effect, 0, 80, and 160 mg/kg body wt Mel dissolved in N-methyl-2-pyrrolidone (NMP) was injected. NMP had no effect on Tb, with Mel again causing a dose-dependent hypothermia. In experiment 2 (n = 30), Mel injected before exposure of layers to heat reduced Tb and prevented heat-induced hyperthermia. Injection after heat stress had begun did not prevent hyperthermia. Under cold stress, Mel induced hypothermia, which was not observed in controls. In experiment 3 (n = 12), Mel injection reduced Tb and increased metatarsal and comb temperatures (but not feathered-skin temperature), respiratory rate, and evaporative water loss. Heart rate rose and then declined, and blood pressure increased 1 h after Mel injection. Heat production rose slightly during the first hour, then decreased in parallel to the Tb decline. We conclude that pharmacological doses of Mel induce hypothermia in hens by increasing nonevaporative skin heat losses and slightly increasing respiratory evaporation.

Tolerance to repeated nicotine administration on performance, subjective, and physiological responses in nonsmokers.

PubMed

Heishman, S J; Henningfield, J E

2000-10-01

When administered acutely to nonsmokers, nicotine's effects on performance are inconsistent, perhaps because of suboptimal dosing or initial dysphoria that could interfere with performance. The purpose of this study was to determine if a range of nicotine doses administered for 8 days to nonsmokers would enhance psychomotor and cognitive abilities and to document the development of nicotine tolerance or sensitization. Twelve male volunteers, who reported ever smoking five cigarettes or less, participated in 8 consecutive experimental days in which they were administered four doses of nicotine polacrilex gum each day in this order: 0, 2, 4, and 8 mg. Performance, subjective, and physiological measures were assessed before and after each dose. Plasma nicotine concentration ranged from 6.9 to 11.5 ng/ml following the 8 mg dose. Nicotine increased rate of responding and decreased response time on working memory (digit recall); however, accuracy was impaired. Nicotine also decreased accuracy on visual scanning and attention (two-letter search), and the 8 mg dose impaired gross motor coordination (circular lights). Tolerance did not develop to the performance impairing effects of nicotine. Nicotine produced dose-related increases in ratings of dysphoria and negative mood, including tension, anxiety, nervousness, turning of stomach, and sedation. Tolerance developed to some, but not all, of these aversive effects. Tolerance also was not observed to the increased cardiovascular measures. Although tolerance developed to some of the aversive effects of nicotine, performance enhancement was not observed. These data do not support the hypothesis that nicotine-induced performance enhancement contributes to the reinforcing effects of tobacco use during the early stages of dependence development.

Leukemia, lymphoma and multiple myeloma mortality (1950-1999) and incidence (1969-1999) in the Eldorado uranium workers cohort.

PubMed

Zablotska, Lydia B; Lane, Rachel S D; Frost, Stanley E; Thompson, Patsy A

2014-04-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932-1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical consequences of initial duloxetine dosing strategies: Comparison of 30 and 60 mg QD starting doses

PubMed Central

Dunner, David L.; Wohlreich, Madelaine M.; Mallinckrodt, Craig H.; Watkin, John G.; Fava, Maurizio

2005-01-01

Background: To reduce the risk for treatment-emergent adverse events and increase patient compliance, clinicians frequently prescribe a suboptimal starting dose of antidepressants, with the goal of increasing the dose once the patient has demonstrated tolerability. Objective: The aim of this study was to examine the tolerability and effectiveness associated with an initial week of duloxetine hydrochloride treatment at 30 mg QD and subsequent dose increase to 60 mg QD, compared with a starting dose of 60 mg QD. Methods: In this open-label study, all patients met the criteria for major depressive disorder (MDD) described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Patients were required to wash out from previous antidepressant medications for 21 days, and were then randomized to receive duloxetine 30 or 60 mg QD for 1 week. After 1 week, patients receiving duloxetine 30 mg QD had their dose increased to 60 mg QD. Patients returned for assessments at weeks 2, 4, 6, 8, and 12. During the remainder of the 12-week study period, the duloxetine dose could be titrated based on the degree of response from 60 mg QD (minimum) to 120 mg QD (maximum), with 90 mg QD as an intermediate dose. Tolerability was assessed by means of discontinuation rates, spontaneously reported adverse events, changes in vital signs, and laboratory tests. Effectiveness measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 core and Maier subscales, individual HAMD17 items, the Hamilton Rating Scale for Anxiety total score, and the Clinical Global Impression of Severity. Results: One hundred thirty-seven patients were enrolled (82 women, 55 men; mean age, 42 years; duloxetine 30 mg QD, 67 patients; duloxetine 60 mg QD, 70 patients). The rate of discontinuation due to adverse events did not differ significantly between patients starting duloxetine at 30 mg QD and 60 mg QD (13.4% vs 18.6%). The most frequently reported adverse events across both treatment groups were nausea, headache, dry mouth, insomnia, and diarrhea. In the first week of treatment, patients receiving duloxetine 30 mg QD had a significantly lower rate of nausea compared with patients receiving 60 mg QD (16.4% vs 32.9%; P = 0.03). Over the 12-week acute-treatment phase, patients starting duloxetine treatment at 30 mg QD had a significantly lower rate of nausea compared with patients initiating treatment at 60 mg QD (P = 0.047). Although between-group differences in the HAMD17 total score were not statistically significant at any visit, patients starting at 30 mg QD experienced significantly less improvement in HAMD17 core and Maier subscales at week 1 compared with patients starting at 60 mg QD (core, P= 0.044; Maier, P = 0.047). After 2 weeks of treatment, the magnitude of improvement among patients starting at 30 mg QD did not differ significantly from that observed in patients who started treatment at 60 mg QD, and there were no significant between-group differences in effectiveness at any subsequent visit. Conclusions: Results from this open-label study in patients with MDD suggest that starting duloxetine treatment at 30 mg QD for 1 week, followed by escalation to 60 mg QD, might reduce the risk for treatment-emergent nausea in these patients while producing only a transitory impact on effectiveness compared with a starting dose of 60 mg QD. PMID:24678074

Irradiation ageing of CSPE/EPR control command electric cables. Correlation between mechanical properties and oxidation

NASA Astrophysics Data System (ADS)

Calmet, J. F.; Carlin, F.; Nguyen, T. M.; Bousquet, S.; Quinot, P.

2002-03-01

In this paper, correlations between the elongation at break and the oxidation of chlorosulfonated polyethylene and ethylene propylene rubber (EPR) polymers in instrumentation and control cables irradiated at different dose rates are brought to evidence. During irradiation, the following phenomena are observed: an increase of oxygen consumption, a degradation of the mechanical properties and a reduction of the oxidation induction time (OIT) measured for EPR. A correlation between the mechanical properties and the OIT of the EPR has only been established in the case of irradiation at low dose rate. This reveals a difference in the oxidative degradation process at low and high dose rates. This study shows the possibility to assess the ageing of electric cables installed inside nuclear power plants by OIT measurements.

[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.

The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model

PubMed Central

Sanzari, Jenine K.; Wan, X. Steven; Krigsfeld, Gabriel S.; Wroe, Andrew J.; Gridley, Daila S.; Kennedy, Ann R.

2014-01-01

Exposure to total-body radiation induces hematological changes, which can detriment one's immune response to wounds and infection. Here, the decreases in blood cell counts after acute radiation doses of γ-ray or proton radiation exposure, at the doses and dose-rates expected during a solar particle event (SPE), are reported in the ferret model system. Following the exposure to γ-ray or proton radiation, the ferret peripheral total white blood cell (WBC) and lymphocyte counts decreased whereas neutrophil count increased within 3 hours. At 48 hours after irradiation, the WBC, neutrophil, and lymphocyte counts decreased in a dose-dependent manner but were not significantly affected by the radiation type (γ-rays verses protons) or dose rate (0.5 Gy/minute verses 0.5 Gy/hour). The loss of these blood cells could accompany and contribute to the physiological symptoms of the acute radiation syndrome (ARS). PMID:25356435

Microdosemeter instrument (MIDN) for assessing risk in space.

PubMed

Pisacane, V L; Dolecek, Q E; Malak, H; Cucinotta, F A; Zaider, M; Rosenfeld, A B; Rusek, A; Sivertz, M; Dicello, J F

2011-02-01

Radiation in space generally produces higher dose rates than that on the Earth's surface, and contributions from primary galactic and solar events increase with altitude within the magnetosphere. Presently, no personnel monitor is available to astronauts for real-time monitoring of dose, radiation quality and regulatory risk. This group is developing a prototypic instrument for use in an unknown, time-varying radiation field. This microdosemeter-dosemeter nucleon instrument is for use in a spacesuit, spacecraft, remote rover and other applications. It provides absorbed dose, dose rate and dose equivalent in real time so that action can be taken to reduce exposure. Such a system has applications in health physics, anti-terrorism and radiation-hardening of electronics as well. The space system is described and results of ground-based studies are presented and compared with predictions of transport codes. An early prototype in 2007 was successfully launched, the only solid-state microdosemeter to have flown in space.

Inhibitory effects of Enteromorpha linza polysaccharide on micronucleus of Allium sativum root cells.

PubMed

Zhang, Zhongshan; Wang, Xiaomei; Li, Jingfen; Liu, Chongbin; Zhang, Quanbin

2016-06-01

In this study, the antimutagenic function of the polysaccharide from Enteromorpha linza with the micronucleus test of Allium sativum root cells induced by sulfur dioxide and ultraviolet was studied. The concentration-effect relation of the two inducers was firstly evaluated. The results showed that an increase of genotoxicity damage was demonstrated and micronuclei frequency induced by sulfur dioxide and ultraviolet displayed dose dependent increases. All the doses of polysaccharide did affect the micronuclei frequency formation compared with the negative control. And also, the significant increase in inhibition rate of micronuclei frequency was observed with the increase of the dose of polysaccharide. It was showed maximum inhibition of micronuclei frequency cells (71.74% and 66.70%) at a concentration of 200g/mL in three experiments. The low molecular weight polysaccharide showed higher inhibition rate than raw polysaccharide at the higher concentration (50g/mL) in the absence of sulfur dioxide and ultraviolet. It was confirmed to be a good mutant inhibitor. Copyright © 2016 Elsevier B.V. All rights reserved.

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

PubMed Central

Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

2012-01-01

Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice.

PubMed

Yu, Kanglun; Doherty, Alison H; Genik, Paula C; Gookin, Sara E; Roteliuk, Danielle M; Wojda, Samantha J; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E; Weil, Michael M; Donahue, Seth W

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Quality factor and dose equivalent investigations aboard the Soviet Space Station Mir

NASA Astrophysics Data System (ADS)

Bouisset, P.; Nguyen, V. D.; Parmentier, N.; Akatov, Ia. A.; Arkhangel'Skii, V. V.; Vorozhtsov, A. S.; Petrov, V. M.; Kovalev, E. E.; Siegrist, M.

1992-07-01

Since Dec 1988, date of the French-Soviet joint space mission 'ARAGATZ', the CIRCE device, had recorded dose equivalent and quality factor values inside the Mir station (380-410 km, 51.5 deg). After the initial gas filling two years ago, the low pressure tissue equivalent proportional counter is still in good working conditions. Some results of three periods are presented. The average dose equivalent rates measured are respectively 0.6, 0.8 and 0.6 mSv/day with a quality factor equal to 1.9. Some detailed measurements show the increasing of the dose equivalent rates through the SAA and near polar horns. The real time determination of the quality factors allows to point out high linear energy transfer events with quality factors in the range 10-20.

In-Situ Strain Analysis of Potential Habitat Composites Exposed to a Simulated Long-Term Lunar Radiation Exposure

NASA Technical Reports Server (NTRS)

Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

2010-01-01

NASA is studying the effects of long-term space radiation on potential multifunctional composite materials for habitats to better determine their characteristics in the harsh space environment. Two composite materials were selected for the study and were placed in a test stand that simulated the stresses of a pressure vessel wall on the material. The samples in the test stand were exposed to radiation at either a fast dose rate or a slow dose rate, and their strain and temperature was recorded during the exposure. It was found that during a fast dose rate exposure the materials saw a decreased strain with time, or a shrinking of the materials. Given previous radiation studies of polymers, this is believed to be a result of crosslinking occurring in the matrix material. However, with a slow dose rate, the materials saw an increase in strain with time, or a stretching of the materials. This result is consistent with scission or degradation of the matrix occurring, possibly due to oxidative degradation.

Hydrogen peroxide kinetics in water radiolysis

NASA Astrophysics Data System (ADS)

Iwamatsu, Kazuhiro; Sundin, Sara; LaVerne, Jay A.

2018-04-01

The kinetics of the formation and reaction of hydrogen peroxide in the long time γ- radiolysis of water is examined using a combination of experiment with model calculations. Escape yields of hydrogen peroxide on the microsecond time scale are easily measured with added radical scavengers even with substantial amounts of initial added hydrogen peroxide. The γ-radiolysis of aqueous hydrogen peroxide solutions without added radical scavengers reach a steady state limiting concentration of hydrogen peroxide with increasing dose, and that limit is directly proportional to the initial concentration of added hydrogen peroxide. The dose necessary to reach that limiting hydrogen peroxide concentration is also proportional to the initial concentration, but dose rate has a very small effect. The addition of molecular hydrogen to aqueous solutions of hydrogen peroxide leads to a decrease in the high dose limiting hydrogen peroxide concentration that is linear with the initial hydrogen concentration, but the amount of decrease is not stoichiometric. Proton irradiations of solutions with added hydrogen peroxide and hydrogen are more difficult to predict because of the decreased yields of radicals; however, with a substantial increase in dose rate there is a sufficient decrease in radical yields that hydrogen addition has little effect on hydrogen peroxide decay.

Antidepressants Alter Cerebrovascular Permeability and Metabolic Rate in Primates

NASA Astrophysics Data System (ADS)

Preskorn, Sheldon H.; Raichle, Marcus E.; Hartman, Boyd K.

1982-07-01

External detection of the annihilation radiation produced by water labeled with oxygen-15 was used to measure cerebrovascular permeability and cerebral blood flow in six rhesus monkeys. Use of oxygen-15 also permitted assessment of cerebral metabolic rate in two of the monkeys. Amitriptyline produced a dose-dependent, reversible increase in permeability at plasma drug concentrations which are therapeutic for depressed patients. At the same concentrations the drug also produced a 20 to 30 percent reduction in cerebral metabolic rate. At higher doses normal autoregulation of cerebral blood flow was suspended, but responsivity to arterial carbon dioxide was normal.

A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors.

PubMed

Bedard, Philippe L; Tabernero, Josep; Janku, Filip; Wainberg, Zev A; Paz-Ares, Luis; Vansteenkiste, Johan; Van Cutsem, Eric; Pérez-García, José; Stathis, Anastasios; Britten, Carolyn D; Le, Ngocdiep; Carter, Kirsten; Demanse, David; Csonka, Denes; Peters, Malte; Zubel, Angela; Nauwelaerts, Heidi; Sessa, Cristiana

2015-02-15

MAPK and PI3K/AKT/mTOR pathways play important roles in many tumors. In this study, safety, antitumor activity, and pharmacokinetics of buparlisib (pan class PI3K inhibitor) and trametinib (MEK inhibitor) were evaluated. This open-label, dose-finding, phase Ib study comprised dose escalation, followed by expansion part in patients with RAS- or BRAF-mutant non-small cell lung, ovarian, or pancreatic cancer. Of note, 113 patients were enrolled, 66 and 47 in dose-escalation and -expansion parts, respectively. MTD was established as buparlisib 70 mg + trametinib 1.5 mg daily [5/15, 33% patients with dose-limiting toxicities (DLT)] and recommended phase II dose (RP2D) buparlisib 60 mg + trametinib 1.5 mg daily (1/10, 10% patients with DLTs). DLTs included stomatitis (8/103, 8%), diarrhea, dysphagia, and creatine kinase (CK) increase (2/103, 2% each). Treatment-related grade 3/4 adverse events (AEs) occurred in 73 patients (65%); mainly CK increase, stomatitis, AST/ALT (aspartate aminotransferase/alanine aminotransferase) increase, and rash. For all (21) patients with ovarian cancer, overall response rate was 29% [1 complete response, 5 partial responses (PR)], disease control rate 76%, and median progression-free survival was 7 months. Minimal activity was observed in patients with non-small cell lung cancer (1/17 PR) and pancreatic cancer (best overall response was SD). Relative to historical data, buparlisib exposure increased and trametinib exposure slightly increased with the combination. At RP2D, buparlisib 60 mg + trametinib 1.5 mg daily shows promising antitumor activity for patients with KRAS-mutant ovarian cancer. Long-term tolerability of the combination at RP2D is challenging, due to frequent dose interruptions and reductions for toxicity. ©2014 American Association for Cancer Research.

Developmental toxicity of CdTe QDs in zebrafish embryos and larvae

NASA Astrophysics Data System (ADS)

Duan, Junchao; Yu, Yongbo; Li, Yang; Yu, Yang; Li, Yanbo; Huang, Peili; Zhou, Xianqing; Peng, Shuangqing; Sun, Zhiwei

2013-07-01

Quantum dots (QDs) have widely been used in biomedical and biotechnological applications. However, few studies focus on the assessing toxicity of QDs exposure in vivo. In this study, zebrafish embryos were treated with CdTe QDs (4 nm) during 4-96 h post-fertilization (hpf). Mortality, hatching rate, malformation, heart rate, and QDs uptake were detected. We also measured the larval behavior to analyze whether QDs had persistent effects on larvae locomotor activity at 144 hpf. The results showed that as the exposure dosages increased, the hatching rate and heart rate of zebrafish embryos were decreased, while the mortality increased. Exposure to QDs caused embryonic malformations, including head malformation, pericardial edema, yolk sac edema, bent spine, and yolk not depleted. QDs fluorescence was mainly localized in the intestines region. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lowest dose (2.5 nM QDs) produced substantial hyperactivity while the higher doses groups (5, 10, and 20 nM QDs) elicited remarkably hypoactivity in dark periods. In summary, the data of this article indicated that QDs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior.

Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

PubMed Central

Claussen, Catherine M; Dafny, Nachum

2016-01-01

The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0 mg/kg) groups were used. Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization were also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively. Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals was observed for the 2.5 and 10.0 mg/kg MPD exposed groups. For 2.5 mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0 mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0 mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and oppositely at ED10 MPD rechallenge. While the behaviorally sensitized animals in general increased in their percentage change of firing rats were observed following acute 10.0 mg/kg MPD and the behaviorally sensitized 10.0 mg/kg MPD animals and a robust increase in neuronal firing rates at ED1 and ED10 rechallenge. These results suggest the need to first individually analyze animal behavioral activity, and than to evaluate the neuronal responses to the drug based on the animals behavioral response to chronic MPD exposure. PMID:26101057

Very low dose gamma irradiation stimulates gaseous exchange and carboxylation efficiency, but inhibits vascular sap flow in groundnut (Arachis hypogaea L.).

PubMed

Ahuja, Sumedha; Singh, Bhupinder; Gupta, Vijay Kumar; Singhal, R K; Venu Babu, P

2014-02-01

An experiment was carried out to determine the effect of low dose gamma radiation on germination, plant growth, nitrogen and carbon fixation and carbon flow and release characteristics of groundnut. Dry seeds of groundnut variety Trombay groundnut 37A (TG 37A), a radio mutant type developed by Bhabha Atomic Research Centre (BARC), Mumbai, India, were subjected to the pre-sowing treatment of gamma radiation within low to high dose physiological range, i.e., 0.0, 0.0082, 0.0164. 0.0328, 0.0656, 0.1312, 5, 25, 100, 500 Gray (Gy) from a cobalt source ((60)Co). Observations were recorded for the radiation effect on percentage germination, vigour, gas exchange attributes such as photosynthetic rate, stomatal conductance and transpiration rate, chlorophyll content, root exudation in terms of (14)C release, vascular sap flow rate and activities of rate defining carbon and nitrogen assimilating enzymes such as ribulose-1,5-bisphosphate carboxylase (rubisco) and nitrate reductase (NR). Seed germination was increased by 10-25% at the lower doses up to 5 Gy while the improvement in plant vigour in the same dose range was much higher (22-84%) than the unirradiated control. For radiation exposure above 5 Gy, a dose-dependent decline in germination and plant vigour was measured. No significant effect was observed on the photosynthesis at radiation exposure below 5 Gy but above 5 Gy dose there was a decline in the photosynthetic rate. Stomatal conductance and transpiration rate, however, were only inhibited at a high dose of 500 Gy. Leaf rubisco activity and NR activities remained unaffected at all the investigated doses of gamma irradiation. Mean root exudation and sap flow rate of the irradiated plants, irrespective of the dose, was reduced over the unirradiated control more so in a dose-dependent manner. Results indicated that a very low dose of gamma radiation, in centigray to gray range, did not pose any threat and in fact stimulated metabolic functions in such a way to aid growth and development of groundnut plants. It further showed that the radiation threshold for the gas exchange traits and rubisco activity, which ultimately determine the plant health and yield, were higher than compared to the other metabolic attributes and were well beyond 500 Gy and that the dose range above 500 Gy should be targeted to measure lethal effects of radiation on carbon assimilation attributes in leguminous crops, in general, and groundnut in particular.

Increase in fluoroscopic radiation dose in successive sessions of multistage Onyx embolization of brain arteriovenous malformations compared with the first session.

PubMed

Sheen, Jae Jon; Jiang, Yuan Yuan; Kim, Young Eun; Maeng, Jun Young; Kim, Tae-Il; Lee, Deok Hee

2018-03-23

Onyx embolization is a treatment for brain arteriovenous malformations (AVMs). However, multistage embolization usually involves the presence of radiodense Onyx cast from the previous sessions, which may influence the fluoroscopic radiation dose. We compared the fluoroscopic dose between the initial and final embolization sessions. From January 2014 to September 2016, 18 patients underwent multistage Onyx embolization (more than twice) for brain AVMs. The total fluoroscopic duration (minutes), dose-area product (DAP, Gy×cm 2 ), and cumulative air kerma (CAK, mGy) of both the frontal and lateral planes were obtained. We compared the frontal and lateral fluoroscopic dose rates (dose/time) of the final embolization session with those of the initial session. The relationship between the injected Onyx volume and radiation dose was tested. The initial and final procedures on the frontal plane showed significantly different fluoroscopic dose rates (DAP: initial 0.668 Gy×cm 2 /min, final 0.848 Gy×cm 2 /min, P=0.02; CAK: initial 12.7 mGy/min, final 23.1 mGy/min, P=0.007). Those on the lateral plane also showed a similar pattern (DAP: initial 0.365 Gy×cm 2 /min, final 0.519 Gy×cm 2 /min, P=0.03; CAK: initial 6.2 mGy/min, final 12.9 mGy/min, P=0.01). The correlation between the cumulative Onyx volume (vials) and radiation dose ratio of both planes showed an increasing trend (rho 0.4325-0.7053; P=0.0011-0.0730). Owing to the automatic exposure control function during fluoroscopy, successive Onyx embolization procedures increase the fluoroscopic radiation dose in multistage brain AVM embolization because of the presence of radiodense Onyx mass. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Detecting structural variances of Co 3O 4 catalysts by controlling beam-induced sample alterations in the vacuum of a transmission electron microscope

DOE PAGES

Kisielowski, C.; Frei, H.; Specht, P.; ...

2016-11-02

This article summarizes core aspects of beam-sample interactions in research that aims at exploiting the ability to detect single atoms at atomic resolution by mid-voltage transmission electron microscopy. Investigating the atomic structure of catalytic Co 3O 4 nanocrystals underscores how indispensable it is to rigorously control electron dose rates and total doses to understand native material properties on this scale. We apply in-line holography with variable dose rates to achieve this goal. Genuine object structures can be maintained if dose rates below ~100 e/Å 2s are used and the contrast required for detection of single atoms is generated by capturing largemore » image series. Threshold doses for the detection of single atoms are estimated. An increase of electron dose rates and total doses to common values for high resolution imaging of solids stimulates object excitations that restructure surfaces, interfaces, and defects and cause grain reorientation or growth. We observe a variety of previously unknown atom configurations in surface proximity of the Co 3O 4 spinel structure. These are hidden behind broadened diffraction patterns in reciprocal space but become visible in real space by solving the phase problem. Finallly, an exposure of the Co 3O 4 spinel structure to water vapor or other gases induces drastic structure alterations that can be captured in this manner.« less

[Immune response to one booster dose of inactivated hepatitis A vaccine in college students].

PubMed

Liao, Z; Feng, X W; Liu, X E; Zhou, Y S; Wen, H R; Peng, S H; Zhang, Y X; Xu, B; Zhuang, H; Chen, H Y

2017-05-10

Objective: To evaluate the safety and immunogenicity of one booster dose of inactivated hepatitis A vaccine in young adults. Methods: The subjects were selected from participants in the clinical trial of immunogenicity of inactivated and attenuated live hepatitis A vaccine in young adults. Eligible subjects were those who had received one dose of inactivated or attenuated hepatitis A vaccine, could be contacted and were sero-negative before primary vaccination. All qualified subjects were immunized with one booster dose of inactivated hepatitis A vaccine. The blood samples were collected before booster dose vaccination and 28 days after the immunization. Anti-HAV antibody titer ≥20 mIU/ml was considered to be sero-protected against hepatitis A virus. Results: The GMCs in the inactivated HAV vaccine group and attenuated live vaccine group before booster dose vaccination were 70.80 mIU/ml and 50.12 mIU/ml, respectively, and the sero-protection rates were 94.7 % and 65.0 % , respectively. After the vaccination of the booster dose, the sero-protection rates in both groups were 100.0 % , and the GMCs were 2 816.09 mIU/ml and 2 654.55 mIU/ml, respectively. Conclusion: The GMCs and sero-protection rates of anti-HAV antibody in young adults declined after three years of the primary vaccination. However, the higher GMC and sero-protection rate were observed in the inactivated vaccine group than in the attenuated live vaccine group. Significant increases of GMC levels were observed in both groups after one booster dose vaccination.

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

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

Strom, Daniel J.

2005-01-14

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

Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: similarities and differences in subjective experiences.

PubMed

Carbonaro, Theresa M; Johnson, Matthew W; Hurwitz, Ethan; Griffiths, Roland R

2018-02-01

Although psilocybin and dextromethorphan (DXM) are hallucinogens, they have different receptor mechanisms of action and have not been directly compared. This study compared subjective, behavioral, and physiological effects of psilocybin and dextromethorphan under conditions that minimized expectancy effects. Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use. Instructions to participants and staff minimized expectancy effects. Various subjective, behavioral, and physiological effects were assessed after drug administration. High doses of both drugs produced similar increases in participant ratings of peak overall drug effect strength, with similar times to maximal effect and time-course. Psilocybin produced orderly dose-related increases on most participant-rated subjective measures previously shown sensitive to hallucinogens. DXM produced increases on most of these same measures. However, the high dose of psilocybin produced significantly greater and more diverse visual effects than DXM including greater movement and more frequent, brighter, distinctive, and complex (including textured and kaleidoscopic) images and visions. Compared to DXM, psilocybin also produced significantly greater mystical-type and psychologically insightful experiences and greater absorption in music. In contrast, DXM produced larger effects than psilocybin on measures of disembodiment, nausea/emesis, and light-headedness. Both drugs increased systolic blood pressure, heart rate, and pupil dilation and decreased psychomotor performance and balance. Psilocybin and DXM produced similar profiles of subjective experiences, with psilocybin producing relatively greater visual, mystical-type, insightful, and musical experiences, and DXM producing greater disembodiment.

Copper deficiency can limit nitrification in biological rapid sand filters for drinking water production.

PubMed

Wagner, Florian B; Nielsen, Peter Borch; Boe-Hansen, Rasmus; Albrechtsen, Hans-Jørgen

2016-05-15

Incomplete nitrification in biological filters during drinking water treatment is problematic, as it compromises drinking water quality. Nitrification problems can be caused by a lack of nutrients for the nitrifying microorganisms. Since copper is an important element in one of the essential enzymes in nitrification, we investigated the effect of copper dosing on nitrification in different biological rapid sand filters treating groundwater. A lab-scale column assay with filter material from a water works demonstrated that addition of a trace metal mixture, including copper, increased ammonium removal compared to a control without addition. Subsequently, another water works was investigated in full-scale, where copper influent concentrations were below 0.05 μg Cu L(-1) and nitrification was incomplete. Copper dosing of less than 5 μg Cu L(-1) to a full-scale filter stimulated ammonium removal within one day, and doubled the filter's removal from 0.22 to 0.46 g NH4-N m(-3) filter material h(-1) within 20 days. The location of ammonium and nitrite oxidation shifted upwards in the filter, with an almost 14-fold increase in ammonium removal rate in the filter's top 10 cm, within 57 days of dosing. To study the persistence of the stimulation, copper was dosed to another filter at the water works for 42 days. After dosing was stopped, nitrification remained complete for at least 238 days. Filter effluent concentrations of up to 1.3 μg Cu L(-1) confirmed that copper fully penetrated the filters, and determination of copper content on filter media revealed a buildup of copper during dosing. The amount of copper stored on filter material gradually decreased after dosing stopped; however at a slower rate than it accumulated. Continuous detection of copper in the filter effluent confirmed a release of copper to the bulk phase. Overall, copper dosing to poorly performing biological rapid sand filters increased ammonium removal rates significantly, achieving effluent concentrations of below 0.01 mg NH4-N L(-1), and had a long-term effect on nitrification performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2018-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("standard") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.

Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; Jesse, Robert; MacLean, Katherine A; Barrett, Frederick S; Cosimano, Mary P; Klinedinst, Maggie A

2017-01-01

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level (“standard”) support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282 PMID:29020861

Morphine tolerance as a function of ratio schedule: response requirement or unit price?

PubMed

Hughes, Christine E; Sigmon, Stacey C; Pitts, Raymond C; Dykstra, Linda A

2005-05-01

Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price.

[Intermediary effectiveness of procaine and procaine metabolites following oral administration].

PubMed

Kaemmerer, K; Kietzmann, M

1989-01-01

The influence of orally administrated procaine hydrochloride and of its metabolites diethylaminoethanol, monoethylaminoethanol and ethanolamine on specific intermediary processes in rats was tested. While the animals got procaine hydrochloride in a single dose or via food the incorporation rate of amino acids in protein was measured in homogenisates of liver tissue by the incorporation of a mixture of 14C-amino acids. Procaine hydrochloride, the commercial product K. H. 3, as well as diethylaminoethanol, monoethylaminoethanol and ethanolamine increased the amino acid incorporation rate in a dose and time dependent mode, while p-aminobenzoic acid remained without any effect. The dose of procaine hydrochloride inducing a maximal reaction was in the range of 50 to 100 mg/kg b. w. (250 to 500 mg/kg food). The minimal active dose was nearly at 10 mg/kg b. w. Paying regard to a metabolic factor of 10 the effective dose-range is nearly the dose used in experience with human beings to influence geriatric complaints. In the study described here haematoporphyrine (a component of the commercial product K. H. 3, not absorbed) shows no specific intermediary effect. May be it promotes the intestinal absorption of procaine hydrochloride by protection against intestinal hydrolysis. The intermediary effect of procaine hydrochloride is to measure on cellular or subcellular level without compatibility to the activity as a local anaesthetic. With regard to other intermediary effects mentioned in the literature like growth promotion or inhibition of monoamine oxidase activity, it is discussed whether the increase of the hepatic amino acid incorporation rate is corresponding to geriatric experiences made with procaine hydrochloride.

Comparison of Effects Produced by Nicotine and the α4β2-Selective Agonist 5-I-A-85380 On Intracranial Self-Stimulation in Rats

PubMed Central

Freitas, Kelen; Carroll, F. Ivy; Negus, S. Stevens

2015-01-01

Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the non-selective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or “facilitation”) of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-ß-erythroidine (DHßE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain- stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHßE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PMID:26461167

Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

PubMed

Graupner, Anne; Eide, Dag M; Brede, Dag A; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H; Bouffler, Simon D; Brunborg, Gunnar; Olsen, Ann Karin

2017-10-01

Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Genotoxic effects of high dose rate X‐ray and low dose rate gamma radiation in ApcMin/+ mice

PubMed Central

Eide, Dag M.; Brede, Dag A.; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H.; Bouffler, Simon D.; Brunborg, Gunnar; Olsen, Ann Karin

2017-01-01

Risk estimates for radiation‐induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc+/+ (wild type) and ApcMin/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60Co‐γ‐rays at a LDR (2.2 mGy h−1) or acutely exposed to 2.6 Gy HDR X‐rays (1.3 Gy min−1). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig‐a gene mutation assay), and levels of DNA lesions (Comet assay, single‐strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3‐ and 10‐fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The ApcMin/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560–569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:28856770

LET spectra measurements from the STS-35 CPDs

NASA Technical Reports Server (NTRS)

1995-01-01

Linear energy transfer (LET) spectra derived form automated track analysis system (ATAS) track parameter measurements for crew passive dosimeters (CPD's) flown with the astronauts on STS-35 are plotted. The spread between the seven individual spectra is typical of past manual measurements of sets of CPD's. This difference is probably due to the cumulative net shielding variations experienced by the CPD's as the astronauts carrying them went about their activities on the Space Shuttle. The STS-35 mission was launched on Dec. 2, 1990, at 28.5 degrees inclination and 352-km altitude. This is somewhat higher than the nominal 300-km flights and the orbit intersects more of the high intensity trapped proton region in the South Atlantic Anomaly (SAA). However, in comparison with APD spectra measured on earlier lower altitude missions (STS-26, -29, -30, -32), the flux spectra are all roughly comparable. This may be due to the fact that the STS-35 mission took place close to solar maximum (Feb. 1990), or perhaps to shielding differences. The corresponding dose and dose equivalent spectra for this mission are shown. The effect of statistical fluctuations at the higher LET values, where track densities are small, is very noticeable. This results in an increased spread within the dose rate and dose equivalent rate spectra, as compared to the flux spectra. The contribution to dose and dose equivalent per measured track is much greater in the high LET region and the differences, though numerically small, are heavily weighted in the integral spectra. The optimum measurement and characterization of the high LET tails of the spectra represent an important part of the research into plastic nuclear track detector (PNTD) response. The integral flux, dose rate, dose equivalent rate and mission dose equivalent for the seven astronauts are also given.

siRNA targeting decoy receptor 3 enhances the sensitivity of gastric carcinoma cells to 5-fluorouracil.

PubMed

Xu, Xiao-Tao; Tao, Ze-Zhang; Song, Qi-Bin; Yao, Yi; Ruan, Peng

2012-09-01

In order to investigate the effects of RNA interference of decoy receptor 3 (DcR3) on the sensitivity of gastric cancer cells to 5-fluorouracil (5-FU) and the relevant mechanisms, siRNA against DcR3 was transfected into the gastric cancer cell line AGS. AGS cells were treated with different doses of 5-FU or for different time periods. The sensitivity of AGS cells to 5-FU was determined. The cell survival rate was detected by MTT assay. The apoptotic rate was determined by DAPI staining, and the expression of related proteins were detected by western blot analysis. The results showed that the cell survival rate was significanlty decreased in the knockdown group compared to the control group at different doses of 5-FU (P<0.01). After different time periods of treatment with 5-FU, the cell survival rate in the knockdown group was significantly decreased compared to the control group, respectively (P<0.01). The apoptotic rate of AGS cells in the knockdown group was increased along with the increasing dose of siRNA. The siRNA against DcR3 enhanced the expression of Fas, FasL, caspase-3 and caspase-8. In conclusion, knockdown of DcR3 by RNA interference enhances apoptosis and inhibits the growth of gastric cancer cells. Downregulation of DcR3 enhances the sensitivity of gastric cancer cells to 5-FU and increased the expression of Fas, FasL and caspase-3/8.

Adequacy of Fixed-Dose Heparin Infusions for Venous Thromboembolism Prevention after Microsurgical Procedures.

PubMed

Bertolaccini, Corinne M; Prazak, Ann Marie B; Agarwal, Jayant; Goodwin, Isak A; Rockwell, W Bradford; Pannucci, Christopher J

2018-05-22

 In microvascular surgery, patients often receive unfractionated heparin infusions to minimize risk for microvascular thrombosis. Patients who receive intravenous (IV) heparin are believed to have adequate prophylaxis against venous thromboembolism (VTE). Whether a fixed dose of IV heparin provides detectable levels of anticoagulation, or whether the "one size fits all" approach provides adequate prophylaxis against VTE remains unknown. This study examined the pharmacodynamics of fixed-dose heparin infusions and the effects of real-time, anti-factor Xa (aFXa) level driven heparin dose adjustments.  This prospective clinical trial recruited adult microvascular surgery patients placed on a fixed-dose (500 units/h) unfractionated heparin infusion during their initial microsurgical procedure. Steady-state aFXa levels, a marker of unfractionated heparin efficacy and safety, were monitored. Patients with out-of-range aFXa levels received protocol-driven real-time dose adjustments. Outcomes of interest included aFXa levels in response to heparin 500 units/h, number of dose adjustments required to achieve goal aFXa levels, time to reach goal aFXa level, and 90-day clinically relevant bleeding and VTE.  Twenty patients were recruited prospectively. None of 20 patients had any detectable level of anticoagulation in response to heparin infusions at 500 units/h. The median number of dose adjustments required to reach goal level was five, and median weight-based dose to reach goal level was 11.8 units/kg/h. Real-time dose adjustments significantly increased the proportion of patients with in-range levels (60 vs. 0%, p  = 0.0001). The 90-day VTE rate was 5% and 90-day clinically relevant bleeding rate was 5%.  Fixed-dose heparin infusions at a rate of 500 units/h do not provide a detectable level of anticoagulation after microsurgical procedures and are insufficient for the majority of patients who require VTE prophylaxis. Weight-based heparin infusions at 10 to 12 units/kg/h deserve future study in patients undergoing microsurgical procedures to increase the proportion of patients receiving adequate VTE prophylaxis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Does unilateral laparoscopic diathermy adjusted to ovarian volume increase the chances of ovulation in women with polycystic ovary syndrome?

PubMed

Sunj, M; Canic, T; Baldani, D P; Tandara, M; Jeroncic, A; Palada, I

2013-09-01

Does unilateral volume-adjusted laparoscopic diathermy increase the chances of ovulation in women with polycystic ovary syndrome (PCOS)? Although unilateral laparoscopic ovarian drilling (ULOD) using adjusted thermal doses was more efficient than bilateral laparoscopic ovarian drilling (BLOD) using fixed doses, the chances of ovulation were improved in patients irrespective of the technique used. The adjustment of the thermal dose to ovarian volume in BLOD increases ovulation and pregnancy rates compared with fixed-dose treatment, but BLOD causes the formation of adhesions, particularly on the left ovary, and increases the risk of damage to ovarian tissue. In contrast, ULOD with a fixed thermal dose minimizes the risk of ovarian tissue damage, and can increase the activity in both right and left ovaries, although this varies in humans and in other species. This prospective, longitudinal, study, between September 2009 and January 2013, included 96 infertile women with PCOS who were unresponsive to clomiphene citrate treatment and had underwent either ULOD or BLOD. After surgery, the groups were followed up for 6 months to assess ovulatory response. Patients were assigned to two groups; one group underwent laparoscopic ovarian drilling of the right ovary alone, while both ovaries were treated in the second group. The ULOD group (n = 49) received thermal doses adjusted to the volume of the right ovary (60 J/cm³). The BLOD group (n = 47) received fixed doses of 600 J per ovary, regardless of its volume. The two treatment groups were matched by the number of participants, age and baseline parameters. The ovulation rate during the first menstrual cycle after LOD was significantly higher in the ULOD group than in the BLOD group [73 versus 49%; absolute risk reduction (ARR), -0.25; 95% confidence interval (CI), -0.44 to -0.03; P = 0.014]. Treatment with ULOD on the right ovary significantly increased the chances of ovulation in patients with a larger right ovary compared with those who had a smaller right ovary (100 versus 36%; ARR, -0.64; 95% CI, -0.84 to -0.37; P = 0.004). Interestingly, the chances of ovulation were also significantly higher in patients in the BLOD group who had a larger right ovary compared with those who had a smaller right ovary (88 versus 33%; ARR, -0.55; 95% CI, -0.73 to -0.28; P = 0.002). The pregnancy rate was also significantly higher in patients with a larger right ovary compared with those with a smaller right ovary, regardless of the treatment group. The 6-month follow-up was too short to demonstrate any long-term differences in the ovulation rates. Future research should therefore extend the follow-up beyond 6 months. Another limitation is that ULOD was used to treat only the right ovary. Future studies should investigate whether ULOD treatment of the larger ovary, whether left or right, would significantly increase the ovulation rate. This study represents an advance in the determination of the optimal laparoscopic treatment for women with PCOS, as it was shown that improved results can be achieved using less thermal energy in volume-adjusted ULOD.

Pathology of Serially Sacrificed Female B6C3F1 Mice Continuously Exposed to Very Low-Dose-Rate Gamma Rays.

PubMed

Tanaka, I B; Komura, J; Tanaka, S

2017-03-01

We have previously reported on life span shortening as well as increased incidence rates in several neoplasms in B6C3F1 mice that were continuously exposed to 21 mGy/day of gamma rays for 400 days. To clarify whether the life shortening was due to early appearance of neoplasms (shortened latency) or increased promotion/progression, 8-week-old female specific-pathogen-free B6C3F1 mice were gamma-ray irradiated at a low dose rate of 20 mGy/day for 400 days. At 100 days postirradiation, 60-90 mice were sacrificed, and thereafter every 100 days alongside the age-matched nonirradiated controls, for 700 days. Additional groups were allowed to live out their natural life span. Pathological examination was performed on all mice to identify lesions, non-neoplastic and neoplastic, as well as to determine the cause of death. Body weights were significantly increased in irradiated mice from sacrifice days 200-500. Incidence rates for spontaneously occurring non-neoplastic lesions, such as adrenal subcapsular cell hyperplasia, fatty degeneration of the liver, atrophy and tubulostromal hyperplasia of the ovaries, were significantly increased in irradiated mice. Significantly increased incidence rates with no shortening of latency periods were observed in irradiated mice for malignant lymphomas, hepatocellular adenomas/carcinomas, bronchioloalveolar adenomas, harderian gland adenoma/adenocarcinoma. Shortened latencies with significantly increased incidence rates were observed for adrenal subcapsular cell adenomas and ovarian neoplasms (tubulostromal adenoma, granulosa cell tumors) in irradiated mice. Life span shortening in mice exposed to 20 mGy/day was mostly due to malignant lymphomas. Multiple primary neoplasms were significantly increased in mice exposed to 20 mGy/day from sacrifice days 400-700 and in the life span group. Our results confirm that continuous low-dose-rate gamma-ray irradiation of female B6C3F1 mice causes both cancer induction (shortened latency) and promotion/progression (early death), depending on the neoplasm's organ/tissue of origin.

Alternative Reinforcer Response Cost Impacts Cocaine Choice in Humans

PubMed Central

Stoops, William W.; Lile, Joshua A.; Glaser, Paul E.A.; Hays, Lon R.; Rush, Craig R.

2011-01-01

Cocaine use disorders are an unrelenting public health concern. Behavioral treatments reduce cocaine use by providing non-drug alternative reinforcers. The purpose of this human laboratory experiment was to determine how response cost for non-drug alternative reinforcers influenced cocaine choice. Seven cocaine-using, non-treatment-seeking subjects completed a crossover, double-blind protocol in which they first sampled doses of intranasal cocaine (5, 10, 20 or 30 mg) and completed a battery of subject-rated and physiological measures. Subjects then made eight discrete choices between the sampled dose and an alternative reinforce (US$0.25). The response cost to earn a cocaine dose was always a fixed ratio (FR) of 100 responses. The response cost for the alternative reinforcer varied across sessions (FR1, FR10, FR100, FR1000). Dose-related increases were observed for cocaine choice. Subjects made fewer drug choices when the FR requirements for the alternative reinforcers were lower than that for drug relative to when the FR requirements were equal to or higher than that for drug. Intranasal cocaine also produced prototypical stimulant-like subject-rated and physiological effects (e.g., increased ratings of Like Drug; elevated blood pressure). These data demonstrate that making alternative reinforcers easier to earn reduces cocaine self-administration, which has implications for treatment efforts. PMID:22015480

Radiation Damage in Si Diodes from Short, Intense Ion Pulses

NASA Astrophysics Data System (ADS)

de Leon, S. J.; Ludewigt, B. A.; Persaud, A.; Seidl, P. A.; Schenkel, T.

2017-10-01

The Neutralized Drift Compression Experiment (NDCX-II) at Berkeley Lab is an induction accelerator studying the effects that concentrated ion beams have on various materials. Charged particle radiation damage was the focus of this research - we have characterized a series of Si diodes using an electrometer and calibrated the diodes response using an 241Am alpha source, both before and after exposing the diodes to 1 MeV He ions in the accelerator. The key part here is that the high intensity pulses from NDCX-II (>1010 ions/cm2 per pulse in <20 ns) enabled a systematic study of dose-rate effects. An example of a dose-rate effect in Si diodes is increased accumulation of defects due to damage from ions that bombard them in a short pulse. This accumulated damage leads to a reduction in the charge collection efficiency and an increase in leakage current. Testing dose-rate effects in Si diodes and other semiconductors is a crucial step in designing sustainable instruments that can encounter high doses of radiation, such as high intensity accelerators, fusion energy experiments and space applications and results from short pulses can inform models of radiation damage evolution. This work was supported by the Office of Science of the US Department of Energy under contract DE-AC0205CH11231.

Biological Effects of Nuclear Explosions (BENE) Domain Guide

DTIC Science & Technology

2012-09-01

DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From – To) Technical Report October 2004-April 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER...greatly increased in the nearby region because increasing amounts of contaminated earth and debris are sucked up into the radioactive cloud. In the case...or a denial scenario involving radioisotopes will be non-uniform exposure with various doses and dose rates producing very large variations in

Cardiovascular effects of pancuronium bromide in mongrel dogs.

PubMed

Reitan, J A; Warpinski, M A

1975-09-01

The cardiovascular effects of a new nondepolarizing muscle relaxant, pancuronium bromide, were studied in mongrel dogs. Small, but significant, increases in mean arterial blood pressure were observed after each of 2 intravenous doses (0.01 mg/kg and 0.1 mg/kg) were given. Heart rate increased significantly in dogs administered the larger dosage, and indexes of ventricular functions demonstrated a trend toward positive cardiac inotrophy after either the large or the small dose.

Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator

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

Schüler, Emil; Trovati, Stefania; King, Gregory

Purpose: A key factor limiting the effectiveness of radiation therapy is normal tissue toxicity, and recent preclinical data have shown that ultra-high dose rate irradiation (>50 Gy/s, “FLASH”) potentially mitigates this effect. However, research in this field has been strongly limited by the availability of FLASH irradiators suitable for small animal experiments. We present a simple methodologic approach for FLASH electron small animal irradiation with a clinically available linear accelerator (LINAC). Methods and Materials: We investigated the FLASH irradiation potential of a Varian Clinac 21EX in both clinical mode and after tuning of the LINAC. We performed detailed FLUKA Monte Carlomore » and experimental dosimetric characterization at multiple experimental locations within the LINAC head. Results: Average dose rates of ≤74 Gy/s were achieved in clinical mode, and the dose rate after tuning exceeded 900 Gy/s. We obtained 220 Gy/s at 1-cm depth for a >4-cm field size with 90% homogeneity throughout a 2-cm-thick volume. Conclusions: We present an approach for using a clinical LINAC for FLASH irradiation. We obtained dose rates exceeding 200 Gy/s after simple tuning of the LINAC, with excellent dosimetric properties for small animal experiments. This will allow for increased availability of FLASH irradiation to the general research community.« less

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.

TU-H-BRC-06: Temperature Simulation of Tungsten and W25Re Targets to Deliver High Dose Rate 10 MV Photons

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

Wang, J; Trovati, S; Loo, B

Purpose: To study the impact of electron beam size, target thickness, and target temperature on the ability of the flattening filter-free mode (FFF) treatment head to deliver high-dose-rate irradiations. Methods: The dose distribution and transient temperature of the X-ray target under 10 MeV electron beam with pulse length of 5 microseconds, and repetition rate of 1000 Hz was studied. A MCNP model was built to calculate the percentage depth dose (PPD) distribution in a water phantom at a distance of 100 cm. ANSYS software was used to run heat transfer simulations. The PPD and temperature for both tungsten and W25Remore » targets for different electron beam sizes (FHWM 0.2, 0.5, 1 and 2 mm) and target thickness (0.2 to 2 mm) were studied. Results: Decreasing the target thickness from 1 mm to 0.5 mm, caused a surface dose increase about 10 percent. For both target materials, the peak temperature was about 1.6 times higher for 0.5 mm electron beam compared to the 1 mm beam after reaching their equilibrium. For increasing target thicknesses, the temperature rise caused by the first pulse is similar for all thicknesses, however the temperature difference for subsequent pulses becomes larger until a constant ratio is reached. The target peak temperature after reaching equilibrium can be calculated by adding the steady state temperature and the amplitude of the temperature oscillation. Conclusion: This work indicates the potential to obtain high dose rate irradiation by selecting target material, geometry and electron beam parameters. W25Re may not outperformed tungsten when the target is thick due to its relatively low thermal conductivity. The electron beam size only affects the target temperature but not the PPD. Thin target is preferred to obtain high dose rate and low target temperature, however, the resulting high surface dose is a major concern. NIH funding:R21 EB015957-01; DOD funding:W81XWH-13-1-0165 BL, PM, PB, and RF are founders of TibaRay, Inc. BL is also a borad member. BL and PM have received research grants from Varian Medical System, Inc. and RaySearch Laboratory. RF is an employee of Siemens Healthcare GmbH.« less

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart.

PubMed

Seawright, John W; Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A; Hauer-Jensen, Martin; Boerma, Marjan

2017-01-01

Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate γ-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart.

Effects of low-dose rate γ-irradiation combined with simulated microgravity on markers of oxidative stress, DNA methylation potential, and remodeling in the mouse heart

PubMed Central

Samman, Yusra; Sridharan, Vijayalakshmi; Mao, Xiao Wen; Cao, Maohua; Singh, Preeti; Melnyk, Stepan; Koturbash, Igor; Nelson, Gregory A.; Hauer-Jensen, Martin; Boerma, Marjan

2017-01-01

Purpose Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a combination of HU and low-dose rate γ-irradiation. Methods Cardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate γ-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate γ-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group. Results The combination of HU and γ-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose γ-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in α-smooth muscle cell actin protein content, collagen type III protein content or % total collagen. Conclusions This study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate γ-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart. PMID:28678877

Radiation exposure and lung disease in today's nuclear world.

PubMed

Deas, Steven D; Huprikar, Nikhil; Skabelund, Andrew

2017-03-01

Ionizing radiation poses important health risks. The per capita annual dose rate has increased in the United States and there is increasing concern for the risks posed by low-dose occupational exposure among workers in nuclear industries and healthcare. Recent nuclear accidents and concern for terrorism have heightened concern for catastrophic, high-dose ionizing radiation exposure. This review will highlight recent research into the risks to lung health posed by ionizing radiation exposure and into potential treatments. Angiotensin-converting enzyme inhibitors and some antioxidants have shown promise as mitigators, to decrease pneumonitis and fibrosis when given after exposure. Studies of survivors of nuclear catastrophes have shown increased risk for lung cancer, especially in nonsmokers. There is evidence for increased lung cancer risk in industrial radiation workers, especially those who process plutonium and may inhale radioactive particles. There does not seem to be an increased risk of lung cancer in healthcare workers who perform fluoroscopic procedures. High-dose ionizing radiation exposure causes pneumonitis and fibrosis, and more research is needed to develop mitigators to improve outcomes in nuclear catastrophes. Long-term, low-dose occupational radiation may increase lung cancer risk. More research to better define this risk could lead to improved safety protocols and screening programs.

Synergistic Effects of Incubation in Rotating Bioreactors and Cumulative Low Dose 60Co γ-ray Irradiation on Human Immortal Lymphoblastoid Cells

NASA Astrophysics Data System (ADS)

Wei, Lijun; Han, Fang; Yue, Lei; Zheng, Hongxia; Yu, Dan; Ma, Xiaohuan; Cheng, Huifang; Li, Yu

2012-11-01

The complex space environments can influence cell structure and function. The research results on space biology have shown that the major mutagenic factors in space are microgravity and ionizing radiation. In addition, possible synergistic effects of radiation and microgravity on human cells are not well understood. In this study, human immortal lymphoblastoid cells were established from human peripheral blood lymphocytes and the cells were treated with low dose (0.1, 0.15 and 0.2 Gy) cumulative 60Co γ-irradiation and simulated weightlessness [obtained by culturing cells in the Rotating Cell Culture System (RCCS)]. The commonly used indexes of cell damage such as micronucleus rate, cell cycle and mitotic index were studied. Previous work has proved that Gadd45 (growth arrest and DNA-damage-inducible protein 45) gene increases with a dose-effect relationship, and will possibly be a new biological dosimeter to show irradiation damage. So Gadd45 expression is also detected in this study. The micronucleus rate and the expression of Gadd45α gene increased with irradiation dose and were much higher after incubation in the rotating bioreactor than that in the static irradiation group, while the cell proliferation after incubation in the rotating bioreactor decreased at the same time. These results indicate synergetic effects of simulated weightlessness and low dose irradiation in human cells. The cell damage inflicted by γ-irradiation increased under simulated weightlessness. Our results suggest that during medium- and long-term flight, the human body can be damaged by cumulative low dose radiation, and the damage will even be increased by microgravity in space.

[Dose-effect relationship of orally administered Pyritinol in the chronic organic brain syndrome (author's transl)].

PubMed

Glatzel, J

1978-08-04

161 patients with the chronic organic brain syndrome (average age 64 years) were treated with various oral doses of Pyritinol for various periods of time. Statistical analysis of the data by means of "Konfigurationsfrequenzanalyse" showed that the success rate of treatment increases significantly with increasing dose and duration of the treatment. This means that the recommended daily dose should be exceeded if - for example at the start of treatment and in severe cases or in hospitalized patients - there is no immediate clear improvement in the condition. From the point of view of method this study shows that a retrospective analysis of a group of patients treated in a clinic can also provide interesting results and appropriately supplement controlled studies.

The Effect of Dose Rate on Composite Durability When Exposed to a Simulated Long-Term Lunar Radiation Environment

NASA Technical Reports Server (NTRS)

Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

2011-01-01

Human exploration of space beyond low Earth orbit (LEO) requires a safe living and working environment for crew. Composite materials are one type of material being investigated by NASA as a multi-functional structural approach to habitats for long-term use in space or on planetary surfaces with limited magnetic fields and atmosphere. These materials provide high strength with the potential for decreased weight and increased radiation protection of crew and electronics when compared with conventional aluminum structures. However, these materials have not been evaluated in a harsh radiation environment, as would be experienced outside of LEO or on a planetary surface. Thus, NASA has been investigating the durability of select composite materials in a long-term radiation environment. Previously, NASA exposed composite samples to a simulated, accelerated 30-year radiation treatment and tensile stresses similar to those of a habitat pressure vessel. The results showed evidence of potential surface oxidation and enhanced cross-linking of the matrix. As a follow-on study, we performed the same accelerated exposure alongside an exposure with a decreased dose rate. The slower dose ]rate is comparable to a realistic scenario, although still accelerated. Strain measurements were collected during exposure and showed that with a fastdose rate, the strain decreased with time, but with a slow ]dose rate, the strain increased with time. After the radiation exposures, samples were characterized via tensile tests, flexure tests, Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC). The results of these tests will be discussed.

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

Subjective and physiological effects, and expired carbon monoxide concentrations in frequent and occasional cannabis smokers following smoked, vaporized, and oral cannabis administration.

PubMed

Newmeyer, Matthew N; Swortwood, Madeleine J; Abulseoud, Osama A; Huestis, Marilyn A

2017-06-01

Although smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis' subjective and physiological effects following multiple administration routes. Subjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ 9 -tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54mg). Participants' subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers' ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers' maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers' maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25-6h post-dose compared to vaporization. All participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers' maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments. Published by Elsevier B.V.

Lack of effect of a booster dose of influenza vaccine in hemodialysis patients.

PubMed

Tanzi, Elisabetta; Amendola, Antonella; Pariani, Elena; Zappa, Alessandra; Colzani, Daniela; Logias, Franco; Perego, Angelo; Zanetti, Alessandro R

2007-08-01

To assess whether the administration of a booster dose of influenza vaccine may enhance immune response in hemodialysis patients, 58 subjects were given two doses of the 2003/2004 season influenza vaccine, 1 month apart. "European Agency for the Evaluation of Medicinal Products" (EMEA) criteria were fully met in terms of percentage of response and of mean-fold increase of hemagglutination inhibiting (HI) antibody titer, but not in terms of seroprotection rates (HI antibody titers > or =1:40). The second vaccine administration did not result in additional increase in seroprotection rate or in geometric mean titers. Protective immune response against the epidemic A/H3N2 Fujian-like strain, antigenically distant from that included in the vaccine (A/Panama/2007/99) was observed in 94.7% of vaccinees protected against the A/H3N2 vaccine strain 1 month after immunization. No adverse reactions were reported during follow-up. The study findings suggest that immune response to influenza vaccination may be suboptimal in hemodialysis patients and that the administration of an additional second dose of vaccine does not improve the humoral response.

Cardiovascular effects of constant rate infusions of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized at equipotent doses of sevoflurane.

PubMed

Moran-Muñoz, Rafael; Valverde, Alexander; Ibancovichi, J A; Acevedo-Arcique, Carlos M; Recillas-Morales, Sergio; Sanchez-Aparicio, Pedro; Osorio-Avalos, Jorge; Chavez-Monteagudo, Julio Raul

2017-07-01

This study evaluated the cardiovascular effects of a constant rate infusion (CRI) of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized with sevoflurane at equipotent doses. Treatments consisted of T1-Lidocaine [loading dose 2 mg/kg body weight (BW), IV, and CRI of 100 μg/kg BW per min] at 1.4% end-tidal of sevoflurane (FE SEV ); T2-Dexmedetomidine (loading dose 2 μg/kg BW, IV, and CRI of 2 μg/kg BW per hour) and FE SEV 1.1%; and T3-Lidocaine-Dexmedetomidine using the same doses of T1 and T2 and FE SEV 0.8%. Constant rate infusion of lidocaine did not induce any cardiovascular changes; lidocaine and dexmedetomidine resulted in cardiovascular effects similar to dexmedetomidine alone. These effects were characterized by a significant ( P < 0.001) decrease in heart rate, cardiac output, cardiac index, oxygen delivery, and pulmonary vascular resistance index, and a significant ( P < 0.001) increase in mean and diastolic arterial pressure, systemic vascular resistance index, pulmonary arterial occlusion pressure and oxygen extraction ratio, compared with baseline values. In conclusion, a CRI of lidocaine combined with dexmedetomidine produces significant cardiovascular changes similar to those observed with dexmedetomidine alone.

Low-dose radiation attenuates chemical mutagenesis in vivo.

PubMed

Kakinuma, Shizuko; Yamauchi, Kazumi; Amasaki, Yoshiko; Nishimura, Mayumi; Shimada, Yoshiya

2009-09-01

The biological effects of low-dose radiation are not only of social concern but also of scientific interest. The radioadaptive response, which is defined as an increased radioresistance by prior exposure to low-dose radiation, has been extensively studied both in vitro and in vivo. Here we briefly review the radioadaptive response with respect to mutagenesis, survival rate, and carcinogenesis in vivo, and introduce our recent findings of cross adaptation in mouse thymic cells, that is, the suppressive effect of repeated low-dose radiation on mutation induction by the alkylating agent N-ethyl-N-nitrosourea.

The methodology study of time accelerated irradiation of elastomers

NASA Astrophysics Data System (ADS)

Ito, Masayuki

2005-07-01

The article studied the methods how to shorten the irradiation time by increasing dose rate without changing the relationship between dose versus properties of degraded samples. The samples used were nine kinds of EPDM which have different compounding formula. The different dose of Co-γ ray was exposed to the samples. The maximum dose was 2 MGy. The reference condition to be compared with two short time test conditions is irradiation of 0.33 kGy/h at room temperature. Two methods shown below were studied as the time-accelerate irradiation conditions.

Initial experience of ArcCHECK and 3DVH software for RapidArc treatment plan verification

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

Infusino, Erminia; Mameli, Alessandra, E-mail: e.infusino@unicampus.it; Conti, Roberto

2014-10-01

The purpose of this study was to perform delivery quality assurance with ArcCHECK and 3DVH system (Sun Nuclear, FL) and to evaluate the suitability of this system for volumetric-modulated arc therapy (VMAT) (RapidArc [RA]) verification. This software calculates the delivered dose distributions in patients by perturbing the calculated dose using errors detected in fluence or planar dose measurements. The device is tested to correlate the gamma passing rate (%GP) and the composite dose predicted by 3DVH software. A total of 28 patients with prostate cancer who were treated with RA were analyzed. RA treatments were delivered to a diode arraymore » phantom (ArcCHECK), which was used to create a planned dose perturbation (PDP) file. The 3DVH analysis used the dose differences derived from comparing the measured dose with the treatment planning system (TPS)-calculated doses to perturb the initial TPS-calculated dose. The 3DVH then overlays the resultant dose on the patient's structures using the resultant “PDP” beams. Measured dose distributions were compared with the calculated ones using the gamma index (GI) method by applying the global (Van Dyk) normalization and acceptance criteria, i.e., 3%/3 mm. Paired differences tests were used to estimate statistical significance of the differences between the composite dose calculated using 3DVH and %GP. Also, statistical correlation by means of logistic regression analysis has been analyzed. Dose-volume histogram (DVH) analysis for patient plans revealed small differences between treatment plan calculations and 3DVH results for organ at risk (OAR), whereas planning target volume (PTV) of the measured plan was systematically higher than that predicted by the TPS. The t-test results between the planned and the estimated DVH values showed that mean values were incomparable (p < 0.05). The quality assurance (QA) gamma analysis 3%/3 mm showed that in all cases there were only weak-to-moderate correlations (Pearson r: 0.12 to 0.74). Moreover, clinically relevant differences increased with increasing QA passing rate, indicating that some of the largest dose differences occurred in the cases of high QA passing rates, which may be called “false negatives.” The clinical importance of any disagreement between the measured and the calculated dose is often difficult to interpret; however, beam errors (either in delivery or in TPS calculation) can affect the effectiveness of the patient dose. Further research is needed to determinate the role of a PDP-type algorithm to accurately estimate patient dose effect.« less

SU-E-T-413: Examining Acquisition Rate for Using MatriXX Ion Chamber Array to Measure HDR Brachytherapy Treatments

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

Wagar, M; Bhagwat, M; O’Farrell, D

2015-06-15

Purpose: There are unique obstacles to implementing the MatriXX ionchamber array as a QA tool in Brachytherapy given that the device is designed for use in the MV energy range. One of the challenges we investigate is the affect of acquisition rates on dose measurement accuracy for HDR treatment plans. Methods: A treatment plan was optimized in Oncentra Brachy TPS to deliver a planar dose to a 5×5cm region at 10mm depth. The applicator was affixed to the surface of the MatriXX array. The plan was delivered multiple times using a Nucleatron HDR afterloader with a 2.9Ci Ir192 source. Formore » each measurement the sampling rate of the MatriXX movie mode was varied (30ms and 500ms). This experiment was repeated with identical parameters, following a source exchange, with an 11.2Ci Ir192 source. Finally, a single snap measurement was acquired. Analysis was preformed to evaluate the fidelity of the dose delivery for each iteration of the experiment. Evaluation was based on the comparison between the measured and TPS predicted dose. Results: Higher sample rates induce a greater discrepancy between the predicted and measured dose. Delivering the plan using a lower activity source also produced greater discrepancy in the measurement due to the increased delivery time. Analyzing the single snap measurement showed little difference from the 500ms integral dose measurement. Conclusion: The advantage of using movie mode for HDR treatment delivery QA is the ability for real time source tracking in addition to dose measurement. Our analysis indicates that 500ms is an optimal frame rate.« less

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

PubMed Central

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-01-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. Trial Registration ClinicalTrials.gov identifier: NCT00465595 PMID:27909165

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-12-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. ClinicalTrials.gov identifier: NCT00465595. © The Author(s) 2016.

Measures against increased environmental radiation dose by the TEPCO Fukushima Dai-ichi NPP accident in some local governments in the Tokyo metropolitan area: focusing on examples of both Kashiwa and Nagareyama cities in Chiba prefecture.

PubMed

Iimoto, T; Fujii, H; Oda, S; Nakamura, T; Hayashi, R; Kuroda, R; Furusawa, M; Umekage, T; Ohkubo, Y

2012-11-01

The accident of the Fukushima Dai-ichi nuclear power plant of Tokyo Electric Power Cooperation (TEPCO) after the great east Japan earthquake (11 March 2011) elevated the background level of environmental radiation in Eastern Japan. Around the Tokyo metropolitan area, especially around Kashiwa and Nagareyama cities, the ambient dose equivalent rate has been significantly increased after the accident. Responding to strong requests from citizens, the local governments started to monitor the ambient dose equivalent rate precisely and officially, about 3 months after the accident had occurred. The two cities in cooperation with each other also organised a local forum supported by three radiation specialists. In this article, the activities of the local governments are introduced, with main focus on radiation monitoring and measurements. Topics are standardisation of environmental radiation measurements for ambient dose rate, dose mapping activity, investigation of foodstuff and drinking water, lending survey meters to citizens, etc. Based on the data and facts mainly gained by radiation monitoring, risk management and relating activity have been organised. 'Small consultation meetings in kindergartens', 'health consultation service for citizens', 'education meeting on radiation protection for teachers, medical staffs, local government staffs, and leaders of active volunteer parties' and 'decontamination activity', etc. are present key activities of the risk management and restoration around the Tokyo metropolitan area.

Increased γ-H2A.X intensity in response to chronic medium-dose-rate γ-ray irradiation.

PubMed

Sugihara, Takashi; Murano, Hayato; Tanaka, Kimio

2012-01-01

The molecular mechanisms of DNA repair following chronic medium-dose-rate (MDR) γ-ray-induced damage remain largely unknown. We used a cell function imager to quantitatively measure the fluorescence intensity of γ-H2A.X foci in MDR (0.015 Gy/h and 0.06 Gy/h) or high-dose-rate (HDR) (54 Gy/h) γ-ray irradiated embryonic fibroblasts derived from DNA-dependent protein kinase mutated mice (scid/scid mouse embryonic fibroblasts (scid/scid MEFs)). The obtained results are as follows: (1) Automatic measurement of the intensity of radiation-induced γ-H2A.X foci by the cell function imager provides more accurate results compared to manual counting of γ-H2A.X foci. (2) In high-dose-rate (HDR) irradiation, γ-H2A.X foci with high fluorescence intensity were observed at 1 h after irradiation in both scid/scid and wild-type MEFs. These foci were gradually reduced through de-phosphorylation at 24 h or 72 h after irradiation. Furthermore, the fluorescence intensity at 24 h increased to a significantly greater extent in scid/scid MEFs than in wild-type MEFs in the G(1) phase, although no significant difference was observed in G(2)/M-phase MEFs, suggesting that DNA-PKcs might be associated with non-homologous-end-joining-dependent DNA repair in the G(1) phase following HDR γ-ray irradiation. (3) The intensity of γ-H2A.X foci for continuous MDR (0.06 Gy/h and 0.015 Gy/h) irradiation increased significantly and in a dose-dependent fashion. Furthermore, unlike HDR-irradiated scid/scid MEFs, the intensity of γ-H2A.X foci in MDR-irradiated scid/scid MEFs showed no significant increase in the G(1) phase at 24 h, indicating that DNA repair systems using proteins other than DNA-PKcs might induce cell functioning that are subjected to MDR γ-ray irradiation. Our results indicate that the mechanism of phosphorylation or de-phosphorylation of γ-H2A.X foci induced by chronic MDR γ-ray irradiation might be different from those induced by HDR γ-ray irradiation.

Shaken baby syndrome and a triple-dose strategy for its prevention.

PubMed

Stewart, Tanya Charyk; Polgar, Denise; Gilliland, Jason; Tanner, David A; Girotti, Murray J; Parry, Neil; Fraser, Douglas D

2011-12-01

Inflicted traumatic brain injury associated with Shaken Baby Syndrome (SBS) is a leading cause of injury mortality and morbidity in infants. A triple-dose SBS prevention program was implemented with the aim to reduce the incidence of SBS. The objectives of this study were to describe the epidemiology of SBS, the triple-dose prevention program, and its evaluation. Descriptive and spatial epidemiologic profiles of SBS cases treated at Children's Hospital, London Health Sciences Centre, from 1991 to 2010 were created. Dose 1 (in-hospital education): pre-post impact evaluation of registered nurse training, with a questionnaire developed to assess parents' satisfaction with the program. Dose 2 (public health home visits): process evaluation of additional education given to new parents. Dose 3 (media campaign): a questionnaire developed to rate the importance of factors on a 7-point Likert scale. These factors were used to create weights for statistical modeling and mapping within a geographic information system to target prevention ads. Forty-three percent of severe infant injuries were intentional. A total of 54 SBS cases were identified. The mean age was 6.7 months (standard deviation, 10.9 months), with 61% of infant males. The mean Injury Severity Score was 26.3 (standard deviation, 5.5) with a 19% mortality rate. Registered nurses learned new information on crying patterns and SBS, with a 47% increase in knowledge posttraining (p < 0.001). Over 10,000 parents were educated in-hospital, a 93% education compliance rate. Nearly all parents (93%) rated the program as useful, citing "what to do when the crying becomes frustrating" as the most important message. Only 6% of families needed to be educated during home visits. Locations of families with a new baby, high population density, and percentage of lone parents were found to be the most important factors for selecting media sites. The spatial analysis revealed six areas needed to be targeted for ad locations. SBS is a devastating intentional injury that often results in poor outcomes for the child. Implementing a triple-dose prevention program that provides education on crying patterns, coping strategies, and the dangers of shaking is key to SBS prevention. The program increased knowledge. Parents rated the program as useful. The media campaign allowed us to extend the primary prevention beyond new parents to help create a cultural change in the way crying, the primary trigger for SBS, is viewed. Targeting our intervention increased the likelihood that our message was reaching the population in greatest need.

Dose-dependent effects of isoflurane and dobutamine on cardiovascular function in dogs with experimental mitral regurgitation.

PubMed

Goya, Seijirow; Wada, Tomoki; Shimada, Kazumi; Hirao, Daiki; Tanaka, Ryou

2018-04-18

To investigate the dose-dependent effects of isoflurane and dobutamine on haemodynamics in dogs with experimentally induced mitral valve insufficiency (MI). Experimental, dose-response study. Six healthy Beagle dogs. Dogs with surgically induced MI were anaesthetized once. First, anaesthesia was maintained at an end-tidal isoflurane concentration (Fe'Iso) 1.0% (ISO1.0) for 20 minutes. Then, dobutamine was infused successively at 2, 4, 8 and 12 μg kg -1 minute -1 (DOB2-12) for 10 minutes at each dose rate. Measurements were recorded at each stage. Dobutamine was discontinued and Fe'Iso was increased to 1.5% (ISO1.5) for 20 minutes. Dobutamine was administered similarly to ISO1.0, and cardiovascular variables were recorded. The same sequence was repeated for Fe'Iso 2.0% (ISO2.0). Aortic pressure (AoP) and left atrial pressure (LAP) were recorded by radiotelemetry. The combination method of the pressure-volume loop analysis and transoesophageal echocardiography was used to measure cardiovascular variables: end-systolic elastance (Ees), effective arterial elastance (Ea), Ea/Ees, forward stroke volume (FSV), heart rate (HR), and cardiac output (CO). High isoflurane concentration resulted in reduced Ees and increased Ea/Ees, which indicated low arterial pressure. High-dose dobutamine administration resulted in increased Ees and FSV at all isoflurane concentrations. In ISO1.5 and ISO2.0, HR was lower at DOB4 than baseline (BL) but increased at DOB12 compared with DOB4. CO increased at ≥ DOB8 compared with BL. In ISO1.5 and ISO2.0, systolic and mean AoP increased at ≥ DOB4 and ≥ DOB8, respectively. LAP did not change under all conditions. The dose-dependent hypotensive effect of isoflurane in MI dogs was mainly derived from the decrease in contractility. Dobutamine increased AoP without increasing LAP by increasing the contractility attenuated by isoflurane. Our findings may improve the cardiovascular management of dogs with MI undergoing general anaesthesia with isoflurane. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

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.

Pain and mean absorbed dose to the pubic bone after radiotherapy among gynecological cancer survivors.

PubMed

Waldenström, Ann-Charlotte; Olsson, Caroline; Wilderäng, Ulrica; Dunberger, Gail; Lind, Helena; al-Abany, Massoud; Palm, Åsa; Avall-Lundqvist, Elisabeth; Johansson, Karl-Axel; Steineck, Gunnar

2011-07-15

To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses ≥ 52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Pain and Mean Absorbed Dose to the Pubic Bone After Radiotherapy Among Gynecological Cancer Survivors

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

Waldenstroem, Ann-Charlotte, E-mail: ann-charlotte.waldenstrom@oncology.gu.se; Department of Oncology, Sahlgrenska University Hospital, Gothenburg; Olsson, Caroline

Purpose: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. Methods and Materials: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. Results: We analyzed data from 650 survivors (participation rate 79%) with median follow-upmore » of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses {>=}52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Conclusions: Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.« less

Increased prandial insulin secretion after administration of a single preprandial oral dose of repaglinide in patients with type 2 diabetes.

PubMed

Owens, D R; Luzio, S D; Ismail, I; Bayer, T

2000-04-01

To examine the dose-related pharmacodynamics and pharmacokinetics of a single preprandial oral dose of repaglinide in patients with type 2 diabetes. A total of 16 Caucasian men with type 2 diabetes participated in two placebo-controlled double-blind randomized cross-over studies. Patients were randomized to receive a single oral dose of repaglinide (0.5, 1.0, and 2.0 mg in study 1 and 4.0 mg in study 2) or placebo (both studies) administered 15 min before the first of two sequential identical standard meals (breakfast and lunch) that were 4 h apart. During each of the study days, which were 1 week apart, blood samples were taken at frequent intervals over a period of approximately 8 h for measurement of plasma glucose, insulin, C-peptide, and repaglinide concentrations. During the first meal period (0-240 min), administration of repaglinide reduced significantly the area under the curve (AUC) for glucose concentration and significantly increased the AUC for insulin levels, C-peptide levels, and the insulin secretion rate. These results, compared with those of administering placebo, were dose dependent and log linear. The effect of repaglinide administration on insulin secretion was most pronounced in the early prandial period. Within 30 min, it caused a relative increase in insulin secretion of up to 150%. During the second meal period (240-480 min), there was no difference between repaglinide and placebo administration in the AUC for glucose concentration, C-peptide concentration, and the estimated insulin secretion rate. A single dose of repaglinide (0.5-4.0 mg) before breakfast improves insulin secretion and reduces prandial hyperglycemia dose-dependently Administration of repaglinide had no effect on insulin secretion with the second meal, which was consumed 4 h after breakfast.

Assessment of monitor unit limiting strategy using volumetric modulated arc therapy for cancer of hypopharynx.

PubMed

Ahamed, Shabbir; Singh, Navin; Gudipudi, Deleep; Mulinti, Suneetha; Talluri, Anil; Soubhagya, Bhudevi; Sresty, Madhusudhana

2017-03-01

To quantify relative merit of MU deprived plans against freely optimized plans in terms of plan quality and report changes induced by progressive resolution optimizer algorithm (PRO3) to the dynamic parameters of RapidArc. Ten cases of carcinoma hypopharynx were retrospectively planned in three phases without using MU tool. Replicas of these baseline plans were reoptimized using "Intermediate dose" feature and "MU tool" to reduce MUs by 20%, 35%, and 50%. Overall quality indices for target and OAR, integral dose, dose-volume spread were assessed. All plans were appraised for changes induced in RapidArc dynamic parameters and pre-treatment quality assurance (QA). With increasing MU reduction strength (MURS), MU/Gy values reduced, for all phases with an overall range of 8.6-34.7%; mean dose rate decreased among plans of each phase, phase3 plans recorded greater reductions. MURS20% showed good trade-off between MUs and plan quality. Dose-volume spread below 5Gy was higher for baseline plans while lower between 20 and 35Gy. Integral dose was lower for MURS0%, not exceeding 1.0%, compared against restrained plans. Mean leaf aperture and control point areas increased systematically, correlated negatively with increasing MURS. Absolute delta dose rate variations were least for MURS0%. MU deprived plans exhibited GAI (>93%), better than MURS0% plans. Baseline plans are superior to MU restrained plans. However, MURS20% offers equivalent and acceptable plan quality with mileage of MUs, improved GAI for complex cases. MU tool may be adopted to tailor treatment plans using PRO3. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter.

PubMed

Spaak, Jonas; Merlocco, Anthony C; Soleas, George J; Tomlinson, George; Morris, Beverley L; Picton, Peter; Notarius, Catherine F; Chan, Christopher T; Floras, John S

2008-02-01

The cardiovascular benefits of light to moderate red wine consumption often have been attributed to its polyphenol constituents. However, the acute dose-related hemodynamic, vasodilator, and sympathetic neural effects of ethanol and red wine have not been characterized and compared in the same individual. We sought to test the hypotheses that responses to one and two alcoholic drinks differ and that red wine with high polyphenol content elicits a greater effect than ethanol alone. Thirteen volunteers (24-47 yr; 7 men, 6 women) drank wine, ethanol, and water in a randomized, single-blind trial on three occasions 2 wk apart. One drink of wine and ethanol increased blood alcohol to 38 +/- 2 and 39 +/- 2 mg/dl, respectively, and two drinks to 72 +/- 4 and 83 +/- 3 mg/dl, respectively. Wine quadrupled plasma resveratrol (P < 0.001) and increased catechin (P < 0.03). No intervention affected blood pressure. One drink had no heart rate effect, but two drinks of wine increased heart rate by 5.7 +/- 1.6 beats/min; P < 0.001). Cardiac output fell 0.8 +/- 0.3 l/min after one drink of ethanol and wine (both P < 0.02) but increased after two drinks of ethanol (+0.8 +/- 0.3 l/min) and wine (+1.2 +/- 0.3 l/min) (P < 0.01). One alcoholic drink did not alter muscle sympathetic nerve activity (MSNA), while two drinks increased MSNA by 9-10 bursts/min (P < 0.001). Brachial artery diameter increased after both one and two alcoholic drinks (P < 0.001). No beverage augmented, and the second wine dose attenuated (P = 0.02), flow-mediated vasodilation. One drink of ethanol dilates the brachial artery without activating sympathetic outflow, whereas two drinks increase MSNA, heart rate, and cardiac output. These acute effects, which exhibit a narrow dose response, are not modified by red wine polyphenols.

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.

[Effect of the nonspecific biogenic stimulators pentoxyl and mumie on metabolic processes].

PubMed

Shvetskiĭ, A G; Vorob'eva, L M

1978-01-01

Unspecific biogenic stimulants (pentoxyl and mummie) accelerated metabolism of nucleic acids and protein in rat liver tissue. After the treatment with the stimulants the rate of lipolysis exceeded that of lipogenesis. Increase in content of lactate was similar if glycogen and glucose-6-phosphate were used as substrates of glycolysis, but it was stimulated 2-3-fold, when glucose was used; the phenomenon appears to be due to activation of hexokinase. As shown by polarographic measurements mitochondrial respiration was increased in all the metabolic states, but increased doses caused an inhibition of phosphorylation apparently due to functional overstrain of mitochondria. Increased doses of the stimulants accelerated also some other metabolic processes studied, but the effects were not dose-dependent. Pentoxyl and mummie apparently increased processes of protein and nuclei acid metabolism and stimulated the energy-providing reactions.

From dust to dose: Effects of forest disturbance on increased inhalation exposure.

PubMed

Whicker, Jeffrey J; Pinder, John E; Breshears, David D; Eberhart, Craig F

2006-09-15

Ecosystem disturbances that remove vegetation and disturb surface soils are major causes of excessive soil erosion and can result in accelerated transport of soils contaminated with hazardous materials. Accelerated wind erosion in disturbed lands that are contaminated is of particular concern because of potential increased inhalation exposure, yet measurements regarding these relationships are lacking. The importance of this was highlighted when, in May of 2000, the Cerro Grande fire burned over roughly 30% of Los Alamos National Laboratory (LANL), mostly in ponderosa pine (Pinus ponderosa) forest, and through areas with soils containing contaminants, particularly excess depleted and natural uranium. Additionally, post-fire thinning was performed in burned and unburned forests on about 25% of LANL land. The first goal of this study was to assess the potential for increased inhalation dose from uranium contaminated soils via wind-driven resuspension of soil following the Cerro Grande Fire and subsequent forest thinning. This was done through analysis of post-disturbance measurements of uranium air concentrations and their relationships with wind velocity and seasonal vegetation cover. We found a 14% average increase in uranium air concentrations at LANL perimeter locations after the fire, and the greatest air concentrations occurred during the months of April-June when wind velocities are highest, no snow cover, and low vegetation cover. The second goal was to develop a methodology to assess the relative contribution of each disturbance type towards increasing public and worker exposure to these resuspended soils. Measurements of wind-driven dust flux in severely burned, moderately burned, thinned, and unburned/unthinned forest areas were used to assess horizontal dust flux (HDF) in these areas. Using empirically derived relationships between measurements of HDF and respirible dust, coupled with onsite uranium soil concentrations, we estimate relative increases in inhalation doses for workers ranging from 15% to 38%. Despite the potential for increased doses resulting from these forest disturbances, the estimated annual dose rate for the public was <1 microSv yr(-1), which is far below the dose limits for public exposures, and the upper-bound dose rate for a LANL worker was estimated to be 140 microSv yr(-1), far below the 5 x 10(4) microSv yr(-1) occupational dose limit. These results show the importance of ecosystem disturbance in increasing mobility of soil-bound contaminants, which can ultimately increase exposure. However, it is important to investigate the magnitude of the increases when deciding appropriate strategies for management and long-term stewardship of contaminated lands.

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

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

Hansen, Deborah K., E-mail: deborah.hansen@fda.hhs.gov; George, Nysia I.; White, Gene E.

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

Image Registration of Cone-Beam Computer Tomography and Preprocedural Computer Tomography Aids in Localization of Adrenal Veins and Decreasing Radiation Dose in Adrenal Vein Sampling

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

Busser, Wendy M. H., E-mail: wendy.busser@radboudumc.nl; Arntz, Mark J.; Jenniskens, Sjoerd F. M.

2015-08-15

PurposeWe assessed whether image registration of cone-beam computed tomography (CT) (CBCT) and contrast-enhanced CT (CE-CT) images indicating the locations of the adrenal veins can aid in increasing the success rate of first-attempts adrenal vein sampling (AVS) and therefore decreasing patient radiation dose.Materials and Methods CBCT scans were acquired in the interventional suite (Philips Allura Xper FD20) and rigidly registered to the vertebra in previously acquired CE-CT. Adrenal vein locations were marked on the CT image and superimposed with live fluoroscopy and digital-subtraction angiography (DSA) to guide the AVS. Seventeen first attempts at AVS were performed with image registration and retrospectivelymore » compared with 15 first attempts without image registration performed earlier by the same 2 interventional radiologists. First-attempt AVS was considered successful when both adrenal vein samples showed representative cortisol levels. Sampling time, dose-area product (DAP), number of DSA runs, fluoroscopy time, and skin dose were recorded.ResultsWithout image registration, the first attempt at sampling was successful in 8 of 15 procedures indicating a success rate of 53.3 %. This increased to 76.5 % (13 of 17) by adding CBCT and CE-CT image registration to AVS procedures (p = 0.266). DAP values (p = 0.001) and DSA runs (p = 0.026) decreased significantly by adding image registration guidance. Sampling and fluoroscopy times and skin dose showed no significant changes.ConclusionGuidance based on registration of CBCT and previously acquired diagnostic CE-CT can aid in enhancing localization of the adrenal veins thereby increasing the success rate of first-attempt AVS with a significant decrease in the number of used DSA runs and, consequently, radiation dose required.« less

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.

Dose determinants in continuous renal replacement therapy.

PubMed

Clark, William R; Turk, Joseph E; Kraus, Michael A; Gao, Dayong

2003-09-01

Increasing attention is being paid to quantifying the dose of dialysis prescribed and delivered to critically ill patients with acute renal failure (ARF). Recent trials in both the intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) realms have suggested that a direct relationship between dose and survival exists for both of these therapies. The purpose of this review, first, is to analyze critically the above-mentioned dose/outcome studies in acute dialysis. Subsequently, the factors influencing dose prescription and delivery are discussed, with the focus on continuous venovenous hemofiltration (CVVH). Specifically, differences between postdilution and predilution CVVH will be highlighted, and the importance of blood flow rate in dose delivery for these therapies will be discussed.

Staying on track: a cluster randomized controlled trial of automated reminders aimed at increasing human papillomavirus vaccine completion.

PubMed

Patel, Ashlesha; Stern, Lisa; Unger, Zoe; Debevec, Elie; Roston, Alicia; Hanover, Rita; Morfesis, Johanna

2014-05-01

To evaluate whether automated reminders increase on-time completion of the three-dose human papillomavirus (HPV) vaccine series. Ten reproductive health centers enrolled 365 women aged 19-26 to receive dose one of the HPV vaccine. Health centers were matched and randomized so that participants received either routine follow-up (control) or automated reminder messages for vaccine doses two and three (intervention). Intervention participants selected their preferred method of reminders - text, e-mail, phone, private Facebook message, or standard mail. We compared vaccine completion rates between groups over a period of 32 weeks. The reminder system did not increase completion rates, which overall were low at 17.2% in the intervention group and 18.9% in the control group (p=0.881). Exploratory analyses revealed that participants who completed the series on-time were more likely to be older (OR=1.15, 95% CI 1.01-1.31), report having completed a four-year college degree or more (age-adjusted OR=2.51, 95% CI 1.29-4.90), and report three or more lifetime sexual partners (age-adjusted OR=3.45, 95% CI 1.20-9.92). The study intervention did not increase HPV vaccine series completion. Despite great public health interest in HPV vaccine completion and reminder technologies, completion rates remain low. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of the eye's surface topography on the total irradiance of ultraviolet radiation on the inner canthus.

PubMed

Birt, Benjamin; Cowling, Ian; Coyne, Steve; Michael, Greg

2007-04-02

Basal cell carcinoma is the most commonly occurring skin cancer in sub tropical climates. The link between ultraviolet radiation (UVR) and basal cell carcinomas (BCC) is strong. Numerous studies have investigated the spatial distribution of BCCs over the head and neck region and the relative UVR dose, with little or no correlation found between the UVR dose and occurrence rates. This is particularly noted in the inner canthus region. The inner canthus' field of view is restricted by the eye brow ridge, eye orbit and the cheek bone. Yet, the occurrence rate here of BCC's when compared to other regions that are more directly exposed to the environment is significantly higher. A possible causal effect for the increase in occurrence rate in this region is the focussed reflection of UVR from the tear film surface associated with the eye not previously considered in earlier studies. This paper investigates the potential for the surface topography of the eye to reflect focussed radiation towards the inner canthus using a ray tracing programme where the analysis is conducted at a cellular level. Defined hot spots, or striations, of increased irradiation were evidenced across the surface of the inner canthus. This increase in irradiation was not observed with macroscopic detectors which also possibly explain why this increased dose has not previously been detected during environmental measurements with large detectors on manikins or humans.

Evaluation of ability of ferulic acid to control growth and fumonisin production of Fusarium verticillioides and Fusarium proliferatum on maize based media.

PubMed

Ferrochio, Laura; Cendoya, Eugenia; Farnochi, María Cecilia; Massad, Walter; Ramirez, María Laura

2013-10-15

The aim of this study was to evaluate the efficacy of ferulic acid (1, 10, 20 and 25 mM) at different water activity (aw) values (0.99, 0.98, 0.96 and 0.93) at 25 °C on growth and fumonisin production by Fusarium verticillioides and Fusarium proliferatum on maize based media. For both Fusarium species, the lag phase significantly decreased (p ≤ 0.001), and the growth rates increased (p ≤ 0.001) at the lowest ferulic acid concentration used (1mM), regardless of the aw. However, high doses of ferulic acid (10 to 25 mM) significantly reduced (p ≤ 0.001) the growth rate of both Fusarium species, regardless of the a(w). In general, growth rate inhibition increased as ferulic acid doses increased and as media aw decreased. Fumonisin production profiles of both Fusarium species showed that low ferulic acid concentrations (1-10mM) significantly increased (p ≤ 0.001) toxin production, regardless of the aw. High doses of ferulic acid (20-25 mM) reduced fumonisin production, in comparison with the controls, by both Fusarium species but they were not statistically significant in most cases. The results show that the use of ferulic acid as a post-harvest strategy to reduce mycotoxin accumulation on maize needs to be discussed. © 2013.

Measuring the effects of supratherapeutic doses of levofloxacin on healthy volunteers using four methods of QT correction and periodic and continuous ECG recordings.

PubMed

Noel, Gary J; Goodman, Daniel B; Chien, Shuchean; Solanki, Bhavna; Padmanabhan, Mukund; Natarajan, Jaya

2004-05-01

A clinical trial was conducted in healthy volunteers using both periodic and continuous ECG recordings to assess the effect of increasing doses of levofloxacin on the QT and QTc interval. Periodic and continuous ECGs were recorded before and after subjects were dosed with placebo and increasing doses of levofloxacin (500 mg, 1000 mg, 1500 mg) that included doses twice the maximum recommended dose of 750 mg in a double-blind, randomized, four-period, four-sequence crossover trial. Mean heart rate (HR) and the QT and QTc interval after dosing with levofloxacin and placebo were compared, and HR-QT interval relationships defined by linear regression analysis were calculated. After single doses of 1000 and 1500 mg of levofloxacin, HR increased significantly, as measured by periodic and continuous ECG recordings. This transient increase occurred at times of peak plasma concentration and was without symptoms. Mean QT intervals after placebo and mean intervals after levofloxacin were indistinguishable. Using periodic ECG recordings, single doses of 1500 mg were associated with small increases in QTc that were statistically significant. In contrast, an effect on QTc was shown only using the Bazett formula with data obtained from continuous ECG recordings. Together with the finding that levofloxacin does not influence HR-QT relationships, these findings suggest that levofloxacin has little effect on prolonging ventricular repolarization and that small increases in HR associated with high doses of levofloxacin contribute to the drug's apparent effect on QTc. Single doses of 1000 or 1500 mg of levofloxacin transiently increase HR without affecting the uncorrected QT interval. Differences in mean QTc after levofloxacin compared to placebo vary depending on the correction formula used and whether the data analyzed are from periodic or continuous ECG recordings. This work suggests that using continuous ECG recordings in assessing QT/QTc effects of drugs may be of value, particularly with drugs that might influence HR.

Fallout, radiation doses near Dounreay, and childhood leukaemia.

PubMed Central

Darby, S C; Doll, R

1987-01-01

Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by an underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by an underestimate of the relative biological efficiency of high as compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to the dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other possible explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease, and exposure to some other, unidentified environmental agent. These findings weigh heavily against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated. PMID:3103820

Evaluation of characteristics of high-energy electron beams using N-isopropyl-acrylamide gel dosimeter

NASA Astrophysics Data System (ADS)

Shih, Tian-Yu; Yen, Tsung-Hsien; Liu, Yan-Lin; Luzhbin, Dmytro; Wu, Jay

2017-11-01

The advantage of electron beam radiotherapy is that the absorbed dose rapidly decreases with the increasing depth, which can prevent damage to deeper organs and tissues. Accurately evaluating the absorbed dose in the superficial tumor is imperative. This study assessed the characteristics of electron beams by using the N-isopropyl-acrylamide (n-NIPAM) gel dosimeter. The n-NIPAM gel was composed of 6% gelatin, 5% monomer, and 2.5% cross-linker with 5 mM tetrakis (hydroxymethyl) phosphonium chloride for deoxygenation. The gel was irradiated with 6-, 9-, and 12-MeV electron beams with dose rates of 100-600 MU/min, respectively. The energy dependence and dose rate dependence were assessed. The beam profiles and percentage depth doses were measured and compared with the results of the Gafchromic film and ionization chamber. The linearity of the n-NIPAM gel under 6-, 9-, and 12-MeV electrons was larger than 0.990 with 2% variation in sensitivity. The sensitivity of the gel under 100-600 MU/min showed 5% variations. The energy and dose rate dependence can be negligible. The beam profiles and percentage depth doses measured by the n-NIPAM gel matched well with the results of the ionization chamber and film. This study reveals the possibility of using the n-NIPAM gel dosimeter for electron beam measurements in clinical radiotherapy.

The Effect of Taraxacum officinale Hydroalcoholic Extract on Blood Cells in Mice

PubMed Central

Modaresi, Mehrdad; Resalatpour, Narges

2012-01-01

Objectives. Dandelion (Taraxacum officinale) is a herbaceous perennial plant of the family Asteraceae and has medicinal and culinary uses. Dandelion has been used as a remedy for anemia, purifing the blood, and providing immune modulation. Therefore, the aim of this study was to investigate the effect of hydro alcoholic extract on blood cells in mice. Methods. Five groups each including ten adult female (Balb/C) mice weighing 30 ± 5 g were chosen. Normal saline was administered as placebo for group, and dandelion hydro alcoholic extract in doses of 50,100, and 200 mg/kg was injected intraperitoneally for 20 days to test groups and the last group was control group.WBC, RBC, HB, HCT, platelet, and other cells were measured with automated cell counter. Main Results. The number of RBC and the rate of HB in three doses of 100 and 200 mg/kg significantly increased (P < 0.05). As compared with control group, the number of WBC in three doses of 50, 100, and 200 mg/kg increased, but it was significantly in 200 mg/kg dandelion treated group as compared with control group(P < 0.05). The rate of platelet in three doses of 50, 100 and 200 mg/kg significantly decreased as compared with control group (P < 0.01). 3 doses of dandelion increased lymphocyte numbers significantly compared with controls. Conclusion. The study indicates efficacy of dandelion extract on RBC and HB in doses of 50, 100, and 200 mg/kg and in 200 mg/kg on WBC to achieve normal body balance. PMID:22844289

Comparison Between Prospectively Electrocardiogram-Gated High-Pitch Mode and Retrospectively Electrocardiogram-Gated Mode for Dual-Source CT Coronary Angiography.

PubMed

Koplay, Mustafa; Celik, Mahmut; Avcı, Ahmet; Erdogan, Hasan; Demir, Kenan; Sivri, Mesut; Nayman, Alaaddin

2015-01-01

We aimed to report the image quality, relationship between heart rate and image quality, amount of contrast agent given to the patients and radiation doses in coronary CT angiography (CTA) obtained by using high-pitch prospectively ECG-gated "Flash Spiral" technique (method A) or retrospectively ECG-gated technique (method B) using 128×2-slice dual-source CT. A total of 110 patients who were evaluated with method A and method B technique with a 128×2-detector dual-source CT device were included in the study. Patients were divided into three groups based on their heart rates during the procedure, and a relationship between heart rate and image quality were evaluated. The relationship between heart rate, gender and radiation dose received by the patients was compared. A total of 1760 segments were evaluated in terms of image quality. Comparison of the relationship between heart rate and image quality revealed a significant difference between heart rate <60 beats/min group and >75 beats/min group whereas <60 beats/min and 60-75 beats/min groups did not differ significantly. The average effective dose for coronary CTA was calculated as 1.11 mSv (0.47-2.01 mSv) for method A and 8.22 mSv (2.19-12.88 mSv) for method B. Method A provided high quality images with doses as low as <1 mSv in selected patients who have low heart rates with a high negative predictive value to rule out coronary artery disease. Although method B increases the amount of effective dose, it provides high diagnostic quality images for patients who have a high heart rate and arrhythmia which makes it is difficult to obtain images.

High dose psilocybin is associated with positive subjective effects in healthy volunteers.

PubMed

Nicholas, Christopher R; Henriquez, Kelsey M; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Hetzel, Scott; Brown, Randall T; Cozzi, Nicholas V; Thomas, Chantelle; Hutson, Paul R

2018-06-01

The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8-36.6 mg; 27.1-54.0 mg; 36.3-59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire. There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience. High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

A comparative study of nuclear magnetic resonance and UV-visible spectroscopy of dose-response for polymer gel dosimeters was performed. Dosimeters were prepared using N-(Isobutoxymethyl) acrylamide (NIBMA) as a new monomer via radiation induced polymerization for use in radiotherapy planning. The prepared dosimeters were irradiated with doses up to 30 Gy at a constant dose rate of 600 MU/min. Using a medical linear accelerator at irradiation energies of 6, 10 and 18 MV photon beam. The nuclear magnetic resonance (NMR), via spin-spin relaxation rate (R2) for water proton surrounding the polymer formulation and UV-Visible spectroscopy, via the optical absorbance measurements of irradiated dosimeters at selected wavelengths of 500 nm, was used to investigate the dose response of NIBMAGAT gel dosimeters. Scavenge of oxygen was done using tetrakis (hydroxymethyl) phosphonium chloride (THPC). The THPC optimum concentration in the dosimeters formulations were 5 and 10 mM for the NMR and optical absorbance measurements respectively. The quantitative investigation of the dosimeters components reveals the selective formulations based on 4% w/w gelatin, 1% w/w NIBMA, 3% w/w BisAAm, 5 or 10 mM THPC and 17% w/w glycerol which significantly increase the dosimeters dose response. The prepared dosimeters were found to be dose rate and photon beam irradiation energy independent. The stability study shows no change in the relaxation rate or in the optical absorbance of the gel dosimeters up to 8 days post-irradiation. The prepared polymer gel dosimeters at the energies of 6, 10 and 18 MV photon beam irradiation in the range of 1-30 Gy have the linearity of the dose response function in the case of R2 is better than in the case of absorbance measurements; correlation coefficient (r2) equals 0.995 and 0.991, respectively. Dose sensitivity, R2 of NIBMAGAT dosimeters (0.0775 s-1 Gy-1). The absorption band intensity increases linearly with a dose sensitivity of 0.016 cm-1 Gy-1. The detection limit of the present dosimeter analyzed by R2 and absorbance measurements is 1 Gy and 2 Gy respectively. The overall uncertainty measurements of dose approve that by using the absorbance measurements the gel is not useful as a dosimeter like as R2 measurements. It could be a new composition of dosimeters successfully utilized for MRI (Magnetic Resonance Imaging) for radiotherapy treatment planning.

Inducing rat brain CYP2D with nicotine increases the rate of codeine tolerance; predicting the rate of tolerance from acute analgesic response.

PubMed

McMillan, Douglas M; Tyndale, Rachel F

2017-12-01

Repeated opioid administration produces analgesic tolerance, which may lead to dose escalation. Brain CYP2D metabolizes codeine to morphine, a bioactivation step required for codeine analgesia. Higher brain, but not liver, CYP2D is found in smokers and nicotine induces rat brain, but not liver, CYP2D expression and activity. Nicotine induction of rat brain CYP2D increases acute codeine conversion to morphine, and analgesia, however the role of brain CYP2D on the effects of repeated codeine exposure and tolerance is unknown. Rats were pretreated with nicotine (brain CYP2D inducer; 1mg/kg subcutaneously) or vehicle (saline; 1ml/kg subcutaneously). Codeine (40-60mg/kg oral-gavage) or morphine (20-30mg/kg oral-gavage) was administered daily and analgesia was assessed daily using the tail-flick reflex assay. Nicotine (versus saline) pretreatment increased acute codeine analgesia (1.32-fold change in AUC 0-60 min ; p<0.05) and the rate of loss of peak analgesia (11.42%/day versus 4.20%; p<0.006) across the first four days of codeine administration (time to negligible analgesia). Inducing brain CYP2D with nicotine did not alter acute morphine analgesia (1.03-fold; p>0.8), or the rate of morphine tolerance (8.1%/day versus 7.6%; p>0.9). The rate of both codeine and morphine tolerance (loss in peak analgesia from day 1 to day 4) correlated with initial analgesic response on day 1 (R=0.97, p<001). Increasing brain CYP2D altered initial analgesia and subsequent rate of tolerance. Variation in an individual's initial response to analgesic (e.g. high initial dose, smoking) may affect the rate of tolerance, and thereby the risk for dose escalation and/or opioid dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

Fruit Flies Provide New Insights in Low-Radiation Background Biology at the INFN Underground Gran Sasso National Laboratory (LNGS).

PubMed

Morciano, Patrizia; Cipressa, Francesca; Porrazzo, Antonella; Esposito, Giuseppe; Tabocchini, Maria Antonella; Cenci, Giovanni

2018-06-04

Deep underground laboratories (DULs) were originally created to host particle, astroparticle or nuclear physics experiments requiring a low-background environment with vastly reduced levels of cosmic-ray particle interference. More recently, the range of science projects requiring an underground experiment site has greatly expanded, thus leading to the recognition of DULs as truly multidisciplinary science sites that host important studies in several fields, including geology, geophysics, climate and environmental sciences, technology/instrumentation development and biology. So far, underground biology experiments are ongoing or planned in a few of the currently operating DULs. Among these DULs is the Gran Sasso National Laboratory (LNGS), where the majority of radiobiological data have been collected. Here we provide a summary of the current scenario of DULs around the world, as well as the specific features of the LNGS and a summary of the results we obtained so far, together with other findings collected in different underground laboratories. In particular, we focus on the recent results from our studies of Drosophila melanogaster, which provide the first evidence of the influence of the radiation environment on life span, fertility and response to genotoxic stress at the organism level. Given the increasing interest in this field and the establishment of new projects, it is possible that in the near future more DULs will serve as sites of radiobiology experiments, thus providing further relevant biological information at extremely low-dose-rate radiation. Underground experiments can be nicely complemented with above-ground studies at increasing dose rate. A systematic study performed in different exposure scenarios provides a potential opportunity to address important radiation protection questions, such as the dose/dose-rate relationship for cancer and non-cancer risk, the possible existence of dose/dose-rate threshold(s) for different biological systems and/or end points and the possible role of radiation quality in triggering the biological response.

Dosimetry for Small Fields in Stereotactic Radiosurgery Using Gafchromic MD-V2-55 Film, TLD-100 and Alanine Dosimeters

PubMed Central

Massillon-JL, Guerda; Cueva-Prócel, Diego; Díaz-Aguirre, Porfirio; Rodríguez-Ponce, Miguel; Herrera-Martínez, Flor

2013-01-01

This work investigated the suitability of passive dosimeters for reference dosimetry in small fields with acceptable accuracy. Absorbed dose to water rate was determined in nine small radiation fields with diameters between 4 and 35 mm in a Leksell Gamma Knife (LGK) and a modified linear accelerator (linac) for stereotactic radiosurgery treatments. Measurements were made using Gafchromic film (MD-V2-55), alanine and thermoluminescent (TLD-100) dosimeters and compared with conventional dosimetry systems. Detectors were calibrated in terms of absorbed dose to water in 60Co gamma-ray and 6 MV x-ray reference (10×10 cm2) fields using an ionization chamber calibrated at a standards laboratory. Absorbed dose to water rate computed with MD-V2-55 was higher than that obtained with the others dosimeters, possibly due to a smaller volume averaging effect. Ratio between the dose-rates determined with each dosimeter and those obtained with the film was evaluated for both treatment modalities. For the LGK, the ratio decreased as the dosimeter size increased and remained constant for collimator diameters larger than 8 mm. The same behaviour was observed for the linac and the ratio increased with field size, independent of the dosimeter used. These behaviours could be explained as an averaging volume effect due to dose gradient and lack of electronic equilibrium. Evaluation of the output factors for the LGK collimators indicated that, even when agreement was observed between Monte Carlo simulation and measurements with different dosimeters, this does not warrant that the absorbed dose to water rate in the field was properly known and thus, investigation of the reference dosimetry should be an important issue. These results indicated that alanine dosimeter provides a high degree of accuracy but cannot be used in fields smaller than 20 mm diameter. Gafchromic film can be considered as a suitable methodology for reference dosimetry. TLD dosimeters are not appropriate in fields smaller than 10 mm diameters. PMID:23671677

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

Volotskova, O; Xu, A; Jozsef, G

Purpose: To investigate the response and dose rate dependence of a scintillation detector over a wide energy range. Methods: The energy dependence of W1 scintillation detector was tested with: 1) 50–225 keV beams generated by an animal irradiator, 2) a Leksell Gamma Knife Perfexion Co-60 source, 3) 6MV, 6FFF, 10FFF and 15MV photon beams, and 4) 6–20MeV electron beams from a linac. Calibrated linac beams were used to deliver 100 cGy to the detector at dmax in water under reference conditions. The gamma-knife measurement was performed in solid water (100 cGy with 16mm collimator). The low energy beams were calibratedmore » with an ion chamber in air (TG-61), and the scintillation detector was placed at the same location as the ionization chamber during calibration. For the linac photon and electron beams, dose rate dependence was tested for 100–2400 and 100–800 MU/min. Results: The scintillation detector demonstrated strong energy dependence in the range of 50–225keV. The measured values were lower than the delivered dose and increased as the energy increased. Therapeutic photon beams showed energy independence with variations less than 1%. Therapeutic electron beams displayed the same sensitivity of ∼2–3% at their corresponding dmax depths. The change in dose-rate of photon and electron beams within the therapeutic energy range did not affect detector output (<0.5%). Measurements acquired with the gamma knife showed that the output data agreed with the delivered dose up to 3%. Conclusion: W1 scintillation detector output has a strong energy dependence in the diagnostic and orthovoltage energy range. Therapeutic photon beams exhibited energy independence with no observable dose-rate dependence. This study may aid in the implementation of a scintillation detector in QA programs by providing energy calibration factors.« less

General Pharmacology of Artesunate, a Commonly used Antimalarial Drug:Effects on Central Nervous, Cardiovascular, and Respiratory System

PubMed Central

Lee, Hyang-Ae; Kim, Ki-Suk

2010-01-01

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR) , and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial) . Thus, it can be concluded that artesunate is safe at clinical therapeutic doses. PMID:24278528

Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys.

PubMed

Koffarnus, Mikhail N; Winger, Gail

2015-07-01

The relatively weak reinforcing effects of nicotine in experimental studies have been attributed to possible aversive effects or the need to space nicotine administrations over time to expose reinforcing effects. This study was designed to determine if the response-maintaining effects of nicotine are increased when availability is spaced through time, and whether nicotine is an effective punisher of remifentanil-maintained responding. Compared to a cocaine reference dose, nicotine dose and timeout (TO) value were varied in eight rhesus monkeys responding for intravenous (i.v.) nicotine on varying fixed-ratio (FR) schedules of reinforcement.The aversive effects of nicotine were evaluated in four animals choosing between a standard dose of remifentanil alone or in combination with one of several doses of nicotine. In three of eight self-administration monkeys, 0.01 mg/kg/inj nicotine did not maintain responding at any FR value. In the other five animals, nicotine-maintained response rates increased with either FR or TO values to a certain point, and then slowed. Maximum nicotine-maintained response rates were much slower than those maintained by cocaine, and demand for nicotine was less than demand for cocaine. Nicotine was an effective punisher of remifentanil-maintained responding at doses ranging from 0.01 to 0.3 mg/kg/inj. Lower punishing dose seemed to be related to the absence of reinforcing effects within subject. There are an order of magnitude individual differences in sensitivity to both the reinforcing and punishing effects of nicotine, and this drug may be unique in being a weak positive reinforcer in small doses and aversive in large doses.

Next-Step Strategies for Panic Disorder Refractory to Initial Pharmacotherapy

PubMed Central

Simon, NM; Otto, MW; Worthington, JJ; Hoge, EA; Thompson, EH; LeBeau, RT; Moshier, SJ; Zalta, AK; Pollack, MH

2010-01-01

Background More data is needed to guide next step interventions for panic disorder refractory to initial intervention. Method This 24-week randomized clinical trial (RCT) consisted of three phases. Phase 1 is a 6-week lead-in with open-label sertraline flexibly dosed to 100mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 is a six-week double blind RCT of (1) increased dose serotonin selective reuptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 is a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to “medication-optimization” (MO) with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent to treat sample in each phase. Results In Phase 1, 20.5% (8/39) achieved remission, and only baseline severity predicted endpoint PDSS (β (SE)= 1.04(0.15), t=6.76, p<0.000). In Phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n=2] vs. increased dose 9%[n=1]: FET p=n.s.). In Phase 3, remission was minimal (MO = 11%; CBT =10%), with a lack of group difference in PDSS reduction (t(df)=0.51(17), p>0.60) consistent with a small effect size (d=0.24). Conclusion Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in non-remitted panic after 12 weeks of an SSRI did not differ, suggesting both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest better predictors of response to specific treatments over time and additional interventions are needed. PMID:19814948

Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.

PubMed

Osterman, Mark T; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D

2014-11-01

Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 μg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 μg/g. Secondary outcomes were continued remission with FC <100 μg/g or <200 μg/g (among patients with pre-randomization values above these levels). The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P = .0496). More patients in the dose escalation group reduced FC to below 100 μg/g (P = .04) and 200 μg/g (P = .005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 μg/g compared with those with FC <200 μg/g (P = .01). Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov number: NCT00652145. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

Extracellular polymers of ozonized waste activated sludge.

PubMed

Liu, J C; Lee, C H; Lai, J Y; Wang, K C; Hsu, Y C; Chang, B V

2001-01-01

Effect of ozonation on characteristics of waste activated sludge was investigated in the current study. Concentrations of cell-bound extracellular polymers (washed ECPs) did not change much upon ozonation, whereas the sum of cell-bound and soluble extracellular polymers (unwashed ECPs) increased with increasing ozone dose. Washed ECPs in original sludge as divided by molecular weight distribution was 39% < 1,000 Da (low MW), 30% from 1,000 to 10,000 Da (medium MW), and 31% > 10,000 Da (high MW). It was observed that the low-MW fraction decreased, and the high-MW fraction increased in ozonized sludge. The unwashed ECPs were characterized as 44% in low MW, 30% in medium MW, and 26% in high MW. Both low-MW and medium-MW fractions of unwashed ECPs decreased while high-MW fraction increased in ozonized sludge. The dewaterability of ozonized sludge, assessed by capillary suction time (CST) and specific resistance to filtration (SRF), deteriorated with ozone dose. The optimal dose of cationic polyelectrolyte increased with increasing ozone dose. The production rate and the accumulated amount of methane gas of ozonized sludge were also higher.

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.

Amphetamine self-administration in light and moderate drinkers.

PubMed

Stanley, Matthew D; Poole, Mégan M; Stoops, William W; Rush, Craig R

2011-03-01

Light and moderate drinkers respond differently to the effects of abused drugs, including stimulants such as amphetamine. The purpose of this study was to determine whether light and moderate drinkers differ in their sensitivity to the reinforcing and subjective effects of d-amphetamine. We hypothesized that moderate drinkers (i.e., participants that reported consuming at least seven alcohol-containing beverages per week) would be more sensitive to the reinforcing and positive subject-rated effects of d-amphetamine than light drinkers. Data from four studies that employed similar d-amphetamine self-administration procedures and subject-rated drug-effect measures were included in the analysis. Light (n = 17) and moderate (n = 16) drinkers sampled placebo, low (8 to 10 mg), and high (16 to 20 mg) doses of oral d-amphetamine administered in eight capsules. Following sampling sessions, participants worked for a maximum of eight capsules, each containing 12.5% of the previously sampled dose, on a modified progressive-ratio schedule of reinforcement. Both active doses of d-amphetamine functioned as a reinforcer in the moderate drinkers, while only the high dose did so in the light drinkers. The moderate drinkers worked for significantly more capsules that contained the high dose of d-amphetamine than did the light drinkers. d-Amphetamine produced prototypical stimulant-like subjective effects (e.g., dose-dependent increases in ratings of Good Effects; Like Drug and Willing to Take Again). Moderate drinkers reported significantly greater subjective effects than the light drinkers. These results are consistent with those from previous laboratory experiments and suggest that moderate alcohol consumption may increase vulnerability to the abuse-related effects of stimulants. Copyright © 2010 by the Research Society on Alcoholism.

Delivery time comparison for intensity-modulated radiation therapy with/without flattening filter: a planning study

NASA Astrophysics Data System (ADS)

Fu, Weihua; Dai, Jianrong; Hu, Yimin; Han, Dongsheng; Song, Yixin

2004-04-01

The treatment delivery time of intensity-modulated radiation therapy (IMRT) with a multileaf collimator (MLC) is generally longer than that of conventional radiotherapy. In theory, removing the flattening filter from the treatment head may reduce the beam-on time by enhancing the output dose rate, and then reduce the treatment delivery time. And in practice, there is a possibility of delivering the required fluence distribution by modulating the unflattened non-uniform fluence distribution. However, the reduction of beam-on time may be discounted by the increase of leaf-travel time and (or) verification-and-recording (V&R) time. Here we investigate the overall effect of flattening filter on the treatment delivery time of IMRT with MLCs implemented in the step and shoot method, as well as with compensators on six hybrid machines. We compared the treatment delivery time with/without flattening filter for ten nasopharynx cases and ten prostate cases by observing the variations of the ratio of the beam-on time, segment number, leaf-travel time and the treatment delivery time with dose rate, leaf speed and V&R time. The results show that, without the flattening filter, the beam-on time reduces for both static MLC and compensator-based techniques; the number of segments and the leaf-travel time increase slightly for the static MLC technique; the relative IMRT treatment delivery time decreases more with lower dose rate, higher leaf speed and shorter V&R overhead time. The absolute treatment delivery time reduction depends on the fraction dose. It is not clinically significant at a fraction dose of 2 Gy for the technique of removing the flattening filter, but becomes significant when the fraction dose is as high as that for radiosurgery.

Advantages of Reduced Prophylaxis after Tubularized Incised Plate Repair of Hypospadias.

PubMed

Zeiai, Said; Nordenskjöld, Agneta; Fossum, Magdalena

2016-10-01

Concerns about antibiotic resistance, adverse drug reactions and questionable medical benefits have led to changes in prophylactic antibiotic management in hypospadias repair at our clinic. In March 2010 our guidelines were changed from continuous prophylaxis for 14 days to 1 dose preoperatively and another at removal of the stent. We analyze the effects of this new regimen. We performed a prospective journal cohort study of all our hypospadias operations from June 2008 to December 2011. We collected data from consecutive patients undergoing primary tubularized incised plate repair and postoperative stent. Patients operated on before March 2010 were compared to those operated on later. End points were postoperative infection requiring antibiotics and any complication that required redo surgery. The study included 113 primary tubularized incised plate repairs with postoperative stents. Patient distribution was the same in both groups. Of 58 patients in the group receiving continuous antibiotic prophylaxis 17 had a complication and/or infection, compared to 9 of 55 patients receiving 2-dose prophylaxis. The infection rate was 5% in the continuous prophylaxis group and 4% in the 2-dose group. In contrast to our expectations, a lower complication rate was observed in the group with lower antibiotic dose without an increased risk of infection. There is little documented evidence concerning benefits of antibiotic prophylaxis for postoperative complications, which gives rise to large variations in clinical practice. In our study lower antibiotic dose did not increase the number of infections, but rather decreased complication rates. We advocate antibiotic prophylaxis with only a 2-dose regimen. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

SU-E-T-159: Characteristics of Fiber-Optic Radiation Sensor for Proton Therapeutic Beam

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

Son, J; Kim, M; Hwang, U

Purpose: A fiber-optic radiation sensor using Cerenkov radiation has been widely studied for use as a dosimeter for proton therapeutic beam. Although the fiber-optic radiation sensor has already been investigated for proton therapeutic, it has been examined relatively little work for clinical therapeutic proton beams. In this study, we evaluated characteristics of a fiber-optic radiation sensor for clinical therapeutic proton beams. We experimentally evaluated dose-rate dependence, dose response and energy dependence for the proton beam. Methods: A fiber-optic radiation sensor was placed in a water phantom. Beams with energies of low, middle and high were used in the passively-scattered protonmore » therapeutic beam at the National Cancer Center in Korea. The sensor consists of two plastic optical fibers (POF). A reference POF and 2 cm longer POF were used to utilize the subtraction method for having sensitive volume. Each POF is optically coupled to the Multi-Anode Photo Multiplier Tube (MAPMT) and the MAPMT signals are processed using National Instruments Data Acquisition System (NI-DAQ). We were investigated dosimetric properties including dose-rate dependence, dose response and energy dependence. Results: We have successfully evaluated characteristics of a fiber optic radiation sensor using Cerenkov radiation. The fiber-optic radiation sensor showed the dose response linearity and low energy dependence. In addition, as the dose-rate was increased, Cerenkov radiation increased linearly. Conclusion: We evaluated the basic characteristics of the fiber optic radiation sensor, the dosimetry tool, to raise the quality of proton therapy. Based on the research, we developed a real time dosimetry system of the optic fiber to confirm the real time beam position and energy for therapeutic proton pencil beam.« less

Fiber-Coupled, Time-Gated { {Al}}_{2}{ {O}}_{3} : { {C}} Radioluminescence Dosimetry Technique and Algorithm for Radiation Therapy With LINACs

NASA Astrophysics Data System (ADS)

Magne, Sylvain; Deloule, Sybelle; Ostrowsky, Aimé; Ferdinand, Pierre

2013-08-01

An original algorithm for real-time In Vivo Dosimetry (IVD) based on Radioluminescence (RL) of dosimetric-grade Al2O3:C crystals is described and demonstrated in reference conditions with 12-MV photon beams from a Saturne 43 linear accelerator (LINAC), simulating External Beam Radiation Therapy (EBRT) treatments. During the course of irradiation, a portion of electrons is trapped within the Al2O3:C crystal while another portion recombines and generates RL, recorded on-line using an optical fiber. The RL sensitivity is dose-dependent and increases in accordance with the concentration of trapped electrons. Once irradiation is completed, the Al2O3:C crystal is reset by laser light (reusable) and the resultant OSL (Optically Stimulated Luminescence) is also collected back by the remote RL-OSL reader and finally integrated to yield the absorbed dose. During irradiation, scintillation and Cerenkov lights generated within the optical fiber (“stem effect”) are removed by a time-discrimination method involving a discriminating unit and a fiber-coupled BGO scintillator placed in the irradiation room, next to the LINAC. The RL signals were then calibrated with respect to reference dose and dose rate data using an ionization chamber (IC). The algorithm relies upon the integral of the RL and provides the accumulated dose (useful to the medical physicist) at any time during irradiation, the dose rate being derived afterwards. It is tested with both step and arbitrary dose rate profiles, manually operated from the LINAC control desk. The doses measured by RL and OSL are both compared to reference doses and deviations are about ±2% and ±1% respectively, thus demonstrating the reliability of the algorithm for arbitrary profiles and wide range of dose rates. Although the calculation was done off-line, it is amenable to real-time processing during irradiation.

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

Miles, Edward F.; Tatsukawa, Yoshimi; Funamoto, Sachiyo

Purpose . There is evidence in the literature of increased maternal radiosensitivity during pregnancy. Materials and Methods . We tested this hypothesis using information from the atomic-bomb survivor cohort, that is, the Adult Health Study database at the Radiation Effects Research Foundation, which contains data from a cohort of women who were pregnant at the time of the bombings of Hiroshima and Nagasaki. Previous evaluation has demonstrated long-term radiation dose-response effects. Results/Conclusions . Data on approximately 250 women were available to assess dose-response rates for serum cholesterol, white blood cell count, erythrocyte sedimentation rate, and serum hemoglobin, and on approximatelymore » 85 women for stable chromosome aberrations, glycophorin A locus mutations, and naïve CD4 T-cell counts. Although there is no statistically significant evidence of increased radiosensitivity in pregnant women, the increased slope of the linear trend line in the third trimester with respect to stable chromosome aberrations is suggestive of an increased radiosensitivity.« less

Randomized trial of betahistine mesilate tablets as augmentation for oxcarbazepine and carbamazepine in treating vestibular paroxysmia.

PubMed

Xue, Hui; Xiang, Wenping; Yu, Yichuan; Liu, Guorong; Chong, Yi; Zhou, Jiying

2018-01-01

Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ) plus betahistine mesilate tablets (BMT) (CBZ+BMT) and oxcarbazepine (OXC) plus BMT (OXC+BMT) in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT. VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed. In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group ( p =0.04). Subgroup analysis found that patients receiving BMT (18 mg) had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg). These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ hypersensitivity, and the synergistic effect could be increased along with the increased dose of BMT.

The Desire to Drink Alcohol is Enhanced with High Caffeine Energy Drink Mixers

PubMed Central

Marczinski, Cecile A.; Fillmore, Mark T.; Stamates, Amy L.; Maloney, Sarah F.

2017-01-01

Background Consumption of alcohol mixed with energy drinks (AmED) has been associated with a variety of risks beyond that observed with alcohol alone. Consumers of AmED beverages are more likely to engage in heavy episodic (binge) drinking. The purpose of this study was to investigate whether the consumption of high caffeine energy drink mixers with alcohol would increase the desire to drink alcohol compared to the same amount of alcohol alone using a double-blind, within-subjects, placebo-controlled study design. Methods Participants (n = 26) of equal gender who were social drinkers attended 6 double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. On each test day, participants received 1 of 6 possible doses: 1) 1.21 ml/kg vodka + 3.63 ml/kg decaffeinated soft drink, 2) 1.21 ml/kg vodka + 3.63 ml/kg energy drink, 3) 1.21 ml/kg vodka + 6.05 ml/kg energy drink, 4) 3.36 ml/kg decaffeinated soft drink, 5) 3.36 ml/kg energy drink, and 6) 6.05 ml/kg energy drink. Following dose administration, participants repeatedly completed self-reported ratings on the Desire for Drug questionnaire and provided breath alcohol readings. Results Alcohol alone increased the subjective ratings of “desire for more alcohol” compared to placebo doses. Energy drink mixers with the alcohol increased desire for more alcohol ratings beyond that observed with alcohol alone. Conclusions This study provides laboratory evidence that AmED beverages lead to greater desire to drink alcohol versus the same amount of alcohol consumed alone. The findings are consistent with results from animal studies indicating that caffeine increases the rewarding and reinforcing properties of alcohol. PMID:27419377

The acute physiological and mood effects of tea and coffee: the role of caffeine level.

PubMed

Quinlan, P T; Lane, J; Moore, K L; Aspen, J; Rycroft, J A; O'Brien, D C

2000-05-01

The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood. Randomised full crossover design in subjects after overnight caffeine abstention was studied. In study 1 (n = 17) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths (1 or 2 cups equivalent). Caffeine levels were 37.5 and 75 mg in tea, 75 and 150 mg in coffee, with water and no-drink controls. In study 2 (n = 15) caffeine level alone was manipulated (water, decaffeinated tea, plus 0, 25, 50, 100, and 200 mg caffeine). Beverage volume and temperature (55 degrees C) were constant. SBP, DBP, heart rate, skin temperature, skin conductance, and mood were monitored over each 3-h study session. In study 1, tea and coffee produced mild autonomic stimulation and an elevation in mood. There were no effects of tea vs. coffee or caffeine dose, despite a fourfold variation in the latter. Increasing beverage strength was associated with greater increases in DBP and energetic arousal. In study 2, caffeinated beverages increased SBP, DBP, and skin conductance and lowered heart rate and skin temperature compared to water. Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature. There were significant effects of caffeine on energetic arousal but no consistent dose-response effects. Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness. Although caffeine can exert dose-dependent effects on a number of acute autonomic responses, caffeine level is not an important factor. Factors besides caffeine may contribute to these acute effects.

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.

Comparison of the Effects of Typical and Atypical Anxiolytics on Learning in Monkeys and Rats,

DTIC Science & Technology

kg) and alprazolam (0.032-0.32 mg/kg) produced dose-dependent decreases in overall response rate in all subjects. However, with buspirone and 8-OH-DPAT...monkeys were variable across drugs and drug classes. Both 8-OH-DPAT and alprazolam produced large increases in percent errors in acquisition at doses

Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury.

PubMed

Wecht, Jill M; Rosado-Rivera, Dwindally; Weir, Joseph P; Ivan, Adrian; Yen, Christina; Bauman, William A

2013-10-01

To determine the effect of an escalating dose of droxidopa (100, 200, and 400 mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effect of droxidopa on (1) supine BP and heart rate, (2) the change in BP and heart rate when these individuals were transferred from the supine to the seated position, and (3) adverse event (AE) reporting. Open-label dose titration trial. A Veterans Administration Medical Center. Participants with SCI (C3-T12) (N=10) were studied during 4 laboratory visits. Subjects visited the laboratory for about 5 hours on each visit, which incorporated a 30-minute seated baseline, a 30- to 60-minute supine, and a 4-hour seated postdrug observation. Placebo on visit 1, droxidopa 100 mg on visit 2, droxidopa 200 mg on visit 3, and droxidopa 400 mg on visit 4. BP and heart rate changes from baseline to the postdrug period, orthostatic heart rate and BP responses, and subjective AE reporting. Seated BP was significantly elevated with 400 mg droxidopa compared with placebo and 100 mg droxidopa for 3 hours and was elevated for 2 hours compared with 200 mg droxidopa. Increase in supine BP was not worsened following droxidopa, and the expected fall in BP when transferred to the seated position was prevented with droxidopa 200 and 400 mg. There were no significant differences in the heart rate response or AE reporting among the study visits. Our preliminary findings suggest that droxidopa, at the doses tested, does not cause excessive increases in supine BP and the 400-mg dose appears to be effective at increasing seated BP for up to 3 hours in persons with SCI. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Radionuclide transfer to wildlife at a 'Reference site' in the Chernobyl Exclusion Zone and resultant radiation exposures.

PubMed

Beresford, N A; Barnett, C L; Gashchak, S; Maksimenko, A; Guliaichenko, E; Wood, M D; Izquierdo, M

2018-02-27

This study addresses a significant data deficiency in the developing environmental protection framework of the International Commission on Radiological Protection, namely a lack of radionuclide transfer data for some of the Reference Animals and Plants (RAPs). It is also the first study that has sampled such a wide range of species (invertebrates, plants, amphibians and small mammals) from a single terrestrial site in the Chernobyl Exclusion Zone (CEZ). Samples were collected in 2014 from the 0.4 km 2 sampling site, located 5 km west of the Chernobyl Nuclear Power complex. We report radionuclide ( 137 Cs, 90 Sr, 241 Am and Pu-isotopes) and stable element concentrations in wildlife and soil samples and use these to determine whole organism-soil concentration ratios and absorbed dose rates. Increasingly, stable element analyses are used to provide transfer parameters for radiological models. The study described here found that for both Cs and Sr the transfer of the stable element tended to be lower than that of the radionuclide; this is the first time that this has been demonstrated for Sr, though it is in agreement with limited evidence previously reported for Cs. Studies reporting radiation effects on wildlife in the CEZ generally relate observations to ambient dose rates determined using handheld dose meters. For the first time, we demonstrate that ambient dose rates may underestimate the actual dose rate for some organisms by more than an order of magnitude. When reporting effects studies from the CEZ, it has previously been suggested that the area has comparatively low natural background dose rates. However, on the basis of data reported here, dose rates to wildlife from natural background radionuclides within the CEZ are similar to those in many areas of Europe. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

An analysis of MCNP cross-sections and tally methods for low-energy photon emitters.

PubMed

Demarco, John J; Wallace, Robert E; Boedeker, Kirsten

2002-04-21

Monte Carlo calculations are frequently used to analyse a variety of radiological science applications using low-energy (10-1000 keV) photon sources. This study seeks to create a low-energy benchmark for the MCNP Monte Carlo code by simulating the absolute dose rate in water and the air-kerma rate for monoenergetic point sources with energies between 10 keV and 1 MeV. The analysis compares four cross-section datasets as well as the tally method for collision kerma versus absorbed dose. The total photon attenuation coefficient cross-section for low atomic number elements has changed significantly as cross-section data have changed between 1967 and 1989. Differences of up to 10% are observed in the photoelectric cross-section for water at 30 keV between the standard MCNP cross-section dataset (DLC-200) and the most recent XCOM/NIST tabulation. At 30 keV, the absolute dose rate in water at 1.0 cm from the source increases by 7.8% after replacing the DLC-200 photoelectric cross-sections for water with those from the XCOM/NIST tabulation. The differences in the absolute dose rate are analysed when calculated with either the MCNP absorbed dose tally or the collision kerma tally. Significant differences between the collision kerma tally and the absorbed dose tally can occur when using the DLC-200 attenuation coefficients in conjunction with a modern tabulation of mass energy-absorption coefficients.

Pharmacokinetics, Pharmacodynamics and Population Pharmacokinetic/Pharmacodynamic Modelling of Bilastine, a Second-Generation Antihistamine, in Healthy Japanese Subjects.

PubMed

Togawa, Michinori; Yamaya, Hidetoshi; Rodríguez, Mónica; Nagashima, Hirotaka

2016-12-01

Bilastine is a novel second-generation antihistamine for the symptomatic treatment of allergic rhinitis and urticaria. The objective of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of bilastine following single and multiple oral doses in healthy Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared with those reported in Caucasian subjects. In a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study, bilastine tablets were administered at single doses of 10, 20, and 50 mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II). After single oral doses, maximum plasma concentrations (C max ) were reached at 1.0-1.5 h postdose. Plasma exposure [C max and area under the plasma concentration-time curve (AUC)] increased dose-proportionally at single doses of 10-50 mg. In repeated-dose administration, no remarkable differences were observed between Day 1 and Day 14 for C max or AUC. For inhibitory effects on wheal and flare response, bilastine 20 and 50 mg showed significant inhibition from 1.5 h after administration as compared with placebo, and the significant effect persisted for 24 h after administration. The rates of adverse events (AEs) were comparable between bilastine and placebo in both Part I and Part II. In addition, no dose- or administration period-dependent tendency of increase in rate of AEs or worsening of severity was observed. Bilastine exhibits similar single- and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy Japanese subjects compared with those observed in Caucasian subjects in previous studies.

Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil.

PubMed

Vila-Nova, Camila; Wehby, George L; Queirós, Fernanda C; Chakraborty, Hrishkesh; Félix, Temis M; Goco, Norman; Moore, Janet; Gewehr, Eduardo V; Lins, Lorene; Affonso, Carla M C; Murray, Jeffrey C

2013-07-01

We report on the risk of miscarriage with high- and low-dosage periconceptional folic acid (FA) supplementation from a double-blind randomized clinical trial for prevention of orofacial cleft recurrence in Brazil. Women at risk of recurrence of orofacial clefts in their offspring were randomized into high (4 mg/day) and low (0.4 mg/day) doses of FA supplementation. The women received the study pills before pregnancy, and supplementation continued throughout the first trimester. Miscarriage rates were compared between the two FA groups and with the population rate. A total of 268 pregnancies completed the study protocol, with 141 in the 4.0-mg group and 127 in the 0.4-mg group. The miscarriage rate was 14.2% in the low-dose FA group (0.4 mg/day) and 11.3% for the high-dose group (4 mg/day) (P=0.4877). These miscarriage rates are not significantly different from the miscarriage rate in the Brazilian population, estimated to be around 14% (P=0.311). These results indicate that high-dose FA does not increase miscarriage risk in this population and add further information to the literature on the safety of high FA supplementation for prevention of birth defect recurrence.

A review of the cohorts with environmental and occupational mineral fiber exposure.

PubMed

Metintas, Selma; Ak, Guntulu; Metintas, Muzaffer

2018-04-20

The aim of the study was to examine factors associated with Malignant Mesothelioma (MM) incidence rate of the groups with occupational asbestos and environmental asbestos or erionite exposure in rural area. In this ecological study, a total of 21 cohort datasets (8 environmental and 13 occupational) were evaluated. Data were analyzed using a multiple linear regression analysis model. In environmental cohorts, the risk of MM incidence was higher in women and people exposed to erionite. In this cohort, the incidence rate of MM increased as the median exposure time increased, while the incidence decreased as the median cumulative exposure dose increased. In occupational cohorts, the incidence rate of MM was positively correlated with the median cumulative exposure dose. The risk of mesothelioma was lower in those exposed to tremolite than others. Environmental asbestos exposure is as important as occupational exposure to develop MM, and it has its own unique exposure features on the risk of MM.

A diamond detector in the dosimetry of high-energy electron and photon beams.

PubMed

Laub, W U; Kaulich, T W; Nüsslin, F

1999-09-01

A diamond detector type 60003 (PTW Freiburg) was examined for the purpose of dosimetry with 4-20 MeV electron beams and 4-25 MV photon beams. Results were compared with those obtained by using a Markus chamber for electron beams and an ionization chamber for photon beams. Dose distributions were measured in a water phantom with the detector connected to a Unidos electrometer (PTW Freiburg). After a pre-irradiation of about 5 Gy the diamond detector shows a stability in response which is better than that of an ionization chamber. The current of the diamond detector was measured under variation of photon beam dose rate between 0.1 and 7 Gy min(-1). Different FSDs were chosen. Furthermore the pulse repetition frequency and the depth of the detector were changed. The electron beam dose rate was varied between 0.23 and 4.6 Gy min(-1) by changing the pulse-repetition frequency. The response shows no energy dependence within the covered photon-beam energy range. Between 4 MeV and 18 MeV electron beam energy it shows only a small energy dependence of about 2%, as expected from theory. For smaller electron energies the response increases significantly and an influence of the contact material used for the diamond detector can be surmised. A slight sublinearity of the current and dose rate was found. Detector current and dose rate are related by the expression i alpha Ddelta, where i is the detector current, D is the dose rate and delta is a correction factor of approximately 0.963. Depth-dose curves of photon beams, measured with the diamond detector, show a slight overestimation compared with measurements with the ionization chamber. This overestimation is compensated for by the above correction term. The superior spatial resolution of the diamond detector leads to minor deviations between depth-dose curves of electron beams measured with a Markus chamber and a diamond detector.

Increased medication compliance of liver transplant patients switched from a twice-daily to a once-daily tacrolimus-based immunosuppressive regimen.

PubMed

Eberlin, M; Otto, G; Krämer, I

2013-01-01

Compliance with immunosuppressive therapy plays a major role in the long-term success of liver transplantation. Thus, the development of strategies to promote compliance of liver transplant patients and its evaluation over time are of particular interest. The main objective of this study was to compare medication compliance rates among liver transplant patients over time after transplantation where switched from a twice- to once-daily tacrolimus-based regimen. Sixty-five liver transplant patients being administered tacrolimus-based therapy were classified into three subgroups with regard to time posttransplantation. Medication compliance with tacrolimus-based therapy was measured using an electronic medication event monitoring system over a 12-month period: for 6 months tacrolimus was administered twice-daily and for 6 months, once-daily. Dosing, taking, and timing compliance as well as drug holidays were compared intra-individually between twice- and once-daily intake and among the three subgroups. In addition, patient compliance and quality of life were evaluated using questionnaires. A per protocol analysis of electronically obtained data showed 63 patients to be eligible. The resulting dosing, taking, and timing compliance rates of the patients were higher during the once-daily dosing period. No significant differences in compliance rates with tacrolimus therapy were observed among three subgroups independent of the dosing regimen. More patients failed the correct timing of the evening compared to the morning dose. Missing doses occurred particularly during weekends. Compliance variables measured by questionnaires (Morisky score, self-report, Medication Experience Scale for Immunosuppressants (MESI) score) and the Hospital Anxiety and Depression Scale score were similar in the two dosing periods. The short-form health survey (SF-36) score was higher with once-daily intake. The high measured compliance rates did not vary significantly dependent upon the time after transplantation. Nevertheless, compliance rates were greater using once-daily tacrolimus dosing. Copyright © 2013 Elsevier Inc. All rights reserved.

Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

PubMed

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered.

Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

PubMed Central

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Background Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. PMID:27073327

Advanced tertiary treatment of municipal wastewater using raw and modified diatomite.

PubMed

Wu, Jinlu; Yang, Y S; Lin, Jinhua

2005-12-09

Advanced technology for more efficient and effective wastewater treatment is always timely needed. The feasibility of using raw and modified diatomite for advanced treatment of secondary sewage effluents (SSE) was investigated in this study. Raw diatomite at a dosing rate of 300 mg/l showed a similar potential as activated carbon for removing most organic pollutants and toxic metals from SSE. Its performance was found poor in removal of arsenic and crop nutrient constituents (e.g. ammoniacal nitrogen and phosphate) and remained unsatisfactory even when the dosing rate increased up to 500 mg/l. Where modified diatomite was in lieu of raw diatomite, the removal efficiency for all target constituents was improved by 20-50%. At the dosing rate of 150 mg/l, modified diatomite enabled the post-treated effluents to satisfy the discharge consents, with the levels of all target constituents below the regulatory limits. Modified diatomite has advantages over raw diatomite in improving removal efficiency and reducing the dosing rate required for satisfactory treatment of SSE. It is concluded that modified diatomite is much more effective and efficient than raw diatomite, as an alternative to activated carbon, for economic treatment of SSE.

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.

Dopaminergic influence on rat tongue function and limb movement initiation.

PubMed

Ciucci, Michelle Renee; Connor, Nadine P

2009-04-01

Altering dopamine synaptic transmission can affect both cranial and limb sensorimotor function, but often to a different degree of severity. We hypothesized that haloperidol has dose-dependent but differential effects on lingual forces, lingual movement rates, and limb movement initiation. We measured average and maximal lingual force, tongue press rate and cataleptic descent time in nine Fischer 344/Brown Norway rats in varied doses of haloperidol. Decreases in lingual force and temporal parameters and increases in cataleptic descent time were related to haloperidol dose. However, they were related to a different degree as the relationships were strong between average force and tongue press rate, moderate between maximal force and tongue press rate, moderate between average force and cataleptic descent time, and weak between maximal force and cataleptic descent time. Elucidating the relationships between the cranial and limb sensorimotor systems in the context of altered dopamine synaptic transmission may assist in developing therapies for conditions such as Parkinson's disease.

Development of a flexible γ-ray detector using a liquid scintillation light guide (LSLG).

PubMed

Nomura, Kiyoshi; Yunoki, Akira; Hara, Masayuki; Morito, Yuko; Fujishima, Akira

2018-04-10

A flexible γ detector using a liquid scintillation light guide (LSLG) was developed. The analyzed pulse height (PHA) spectrum depended on the diameter, length and scintillator concentration of the LSLG, and the distance of a γ ray irradiation point from the head of photomultiplier tube (PMT). From the analysis of PHA spectrum, it was found that the count ratio of two divided channel regions linearly decreases as the distance from the PMT head increases. It was further found that the radiation dose rate can be estimated by setting the flexible LSLG tube to a circular shape since the count rate is proportional to the dose rate measured by a conventional NaI (Tl) scintillation detector. Therefore, a flexible and long LSLG detector using a single PMT is useful for determination of the dose rate and has a potential to detect local contaminations in a certain narrow space. Copyright © 2018. Published by Elsevier Ltd.

Developmental inhibition of gamma irradiation on the peach fruit moth Carposina sasakii (Lepidoptera: Carposinidae)

NASA Astrophysics Data System (ADS)

Ryu, Jihoon; Ahn, Jun-Young; Sik Lee, Seung; Lee, Ju-Woon; Lee, Kyeong-Yeoll

2015-01-01

Ionizing irradiation is a useful technique for disinfestation under plant quarantine as well as post-harvest management. Effects of gamma irradiation treatment were tested on different developmental events of Carposina sasakii, which is a serious pest of various orchard crops. Apple fruits infested by C. sasakii were irradiated by gamma rays ranging from 0 to 300 Gy. Inhibition rates were determined on behavioral events related to development, including larval exit from apples, cocoon formation, adult eclosion, and oviposition. Failure rates of all these developmental events increased with increasing doses of irradiation. Rates of larval exit from apples and cocoon formation decreased to 13.2% and 1.7%, respectively, at 300 Gy. However, the adult eclosion rate decreased to 5.4% at 100 Gy and was completely inhibited at doses greater than 150 Gy. LD99 values for the inhibition of cocoon formation and adult emergence was estimated into 313.4 and 191.0 Gy. Furthermore, adults developed from irradiated larvae completely failed to lay eggs. Thus, irradiation of infested apples at doses of 200 Gy and higher completely inhibited the next generation of C. sasakii. Our results suggest that gamma irradiation treatment would be a promising technique for the control of C. sasakii.

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

Sperm Oxidative Stress Is Detrimental to Embryo Development: A Dose-Dependent Study Model and a New and More Sensitive Oxidative Status Evaluation

PubMed Central

de Castro, Letícia S.; de Assis, Patrícia M.; Siqueira, Adriano F. P.; Hamilton, Thais R. S.; Mendes, Camilla M.; Losano, João D. A.; Nichi, Marcílio; Visintin, José A.; Assumpção, Mayra E. O. A.

2016-01-01

Our study aimed to assess the impact of sperm oxidative stress on embryo development by means of a dose-dependent model. In experiment 1, straws from five bulls were subjected to incubation with increasing H2O2 doses (0, 12.5, 25, and 50 μM). Motility parameters were evaluated by Computed Assisted System Analysis (CASA). Experiment 2 was designed to study a high (50 μM) and low dose (12.5 μM) of H2O2 compared to a control (0 μM). Samples were incubated and further used for in vitro fertilization. Analyses of motility (CASA), oxidative status (CellROX green and 2'-7' dichlorofluorescein diacetate), mitochondrial potential (JC-1), chromatin integrity (AO), and sperm capacitation status (chlortetracycline) were performed. Embryos were evaluated based on fast cleavage (30 h.p.i.), cleavage (D = 3), development (D = 5), and blastocyst rates (D = 8). We observed a dose-dependent deleterious effect of H2O2 on motility and increase on the percentages of positive cells for CellROX green, capacitated sperm, and AO. A decrease on cleavage and blastocyst rates was observed as H2O2 increased. Also, we detected a blockage on embryo development. We concluded that sperm when exposed to oxidative environment presents impaired motility traits, prooxidative status, and premature capacitation; such alterations resulting in embryo development fail. PMID:26770658

[Mathematic modeling for prediction of waning immunity and timing of booster doses].

PubMed

Matuo, Fujio; Okada, Kenji

2008-10-01

Under an environment that a vaccination rate is low and an infectious disease is prevalent, it is thought that most vaccinee got additional immunity by natural infection. On the other hand, in the area where the incidence of disease has been reduced by high rate vaccination, it is also decreased the chance of additional immunity by natural infection. Therefore susceptible individuals are increased because of the waning immunity. In the community where a vaccination rate is high, it may be necessary to consider the booster vaccination for adolescent and adult even if one completed the primary vaccinations. It may also be important to explore the timing of booster dose. In this paper, we attempt to give a comprehensive explanation of mathematical model for predicting the antibody duration, and we introduce the role of mathematical model on a consideration to the need and timing of booster doses after the primary series.

Reactogenicity of tetanus, diphtheria, 5-component acellular pertussis vaccine administered as a sixth consecutive acellular pertussis vaccine dose to adolescents.

PubMed

Liese, Johannes G; Rieber, Nikolaus; Malzer, Thomas; Ocak, Marion; Johnson, David R; Decker, Michael D

2010-12-01

Safety of a sixth consecutive dose of acellular pertussis vaccine in adolescents was assessed in a 2-armed, randomized study. Adolescents who had received 5 doses of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (6-dose group) received 1 dose of reduced 5-component acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid (Tdap). Adolescents who had received a primary series of 3 doses of whole-cell pertussis and 1 acellular or whole-cell pertussis booster received 1 dose of Tdap vaccine (5-dose group). Of 214 participants, 176 (82%) reported an injection-site reaction with pain (80%), erythema (22%), and swelling (19%) most frequently reported. A systemic reaction was reported by 169 of 214 (79%) with myalgia (66%), headache (42%), malaise (39%), and fever (9%) most frequently reported. The overall rate of solicited reactions was lower in the 6-dose group than in the 5-dose group (for injection-site reactions: 76.1% vs. 89.7%; for systemic reactions 72.6% vs. 86.6%). Significant differences were observed for injection-site pain, erythema, and for grade 1 or grade 2 increases in arm circumference. Fever, myalgia, and headache were reported at a significantly lower rate in the 6-dose group. Swelling >10 cm was observed in 5 patients (2%), 4 in the 5-dose group. Tdap vaccine was safe when given to adolescents who had received 5 prior doses of acellular pertussis vaccine.

Tuning the third-order nonlinear optical properties of In:ZnO thin films by 8 MeV electron beam irradiation

NASA Astrophysics Data System (ADS)

Shettigar, Nayana; Pramodini, S.; Kityk, I. V.; Abd-Lefdil, M.; Eljald, E. M.; Regragui, M.; Antony, Albin; Rao, Ashok; Sanjeev, Ganesh; Ajeyakashi, K. C.; Poornesh, P.

2017-11-01

We report the third-order nonlinear optical properties of electron beam treated Indium doped ZnO (Zn1-xInxO (x = 0.03) thin films at different dose rate. Zn1-xInxO (x = 0.03) thin films prepared by spray pyrolysis deposition technique were irradiated using 8 MeV electron beam at dose rates ranging from 1 kGy to 4 kGy. X-ray diffraction patterns were obtained to examine the structural changes, The transformation from sphalerite to wurtzite structure of ZnO was observed which indicates occurrence of structural changes due to irradiation. Morphology of irradiated thin films examined using atomic force microscopy (AFM) technique indicates the surface roughness varying with irradiation dose rate. The switching over from Saturable Absorption (SA) to Reverse Saturable Absorption (RSA) behaviour was noted when the irradiation dose rate was increased from 1 kGy to 4 kGy. The significant changes observed in the third-order nonlinear optical susceptibility χ(3) of the Zn1-xInxO (x = 0.03) thin films is attributed mainly due to electron beam irradiation. The study indicates that nonlinear optical parameters can be controlled by electron beam irradiation by choosing appropriate dose rate which is very much essential for device applications. Hence Zn1-xInxO (x = 0.03) materialize as a promising material for use in nonlinear optical device applications.

Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats.

PubMed

Eguale, Tadesse; Chaka, Hassen; Gizaw, Daniel

2009-10-01

A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.

Multiscale analysis of the radiooxidative degradation of EVA/EPDM composites. ATH filler and dose rate effect

NASA Astrophysics Data System (ADS)

Sidi, Ahmedou; Colombani, Juliette; Larché, Jean-François; Rivaton, Agnès

2018-01-01

This study is focused on the radiooxidative degradation of polymeric insulation of electric cables used in Nuclear Power Plants (NPPs). In order to investigate the degradation mechanisms of the insulation, model composites with ATH (Aluminium TriHydrate) filler and blends (without filler) based on a cross-linked mixture of EVA (Ethylene Vinyl Acetate) and EPDM (Ethylene Propylene Diene Monomer) were submitted to gamma-rays. In normal operating conditions of a NPP, the dose rate which electric cables are exposed to is around 0.1 Gy h-1. In this work, artificial accelerated ageing test process has been applied at a relatively low dose rate of 7 Gy h-1. Gamma-irradiations at higher dose rates typically used to accelerate the ageing, in the range 0.2-1 kGy h-1, were also carried out. The first part of the study is focused on irradiations performed at relatively low dose rate and is devoted to the highlighting of the radiooxidative degradation mechanisms of EVA/EPDM blend with and without ATH filler. Correlations between the evolutions of the chemical, morphological and mechanical/electrical properties of the materials occurring after the ageing process are presented. It is shown that the degradation process is governed by radical oxidation mechanism involving chain scissions leading to the formation of carboxylic acids as end-groups. One of the main effects of the ATH filler is the progressive loss of the mechanical properties of the composite upon radiooxidation whereas they are maintained in the case of the unfilled sample. Despite the oxidation of the polymer, no change in the electrical properties of the blend and of the composite could be observed. The second part of the study focuses on the dose rate effect. It is shown that one of the main consequences of an increase of the dose rate from 7 Gy h-1 to 0.2-1 kGy h-1 is a reduction of the chain scission process yield by a factor of about 20. Therefore, an important and consistent finding is that there are some limits that must not be exceeded in terms of dose rate to ensure a global satisfactorily representativeness of the accelerated ageing process.

Role of neuropeptide Y in renal sympathetic vasoconstriction: studies in normal and congestive heart failure rats.

PubMed

DiBona, G F; Sawin, L L

2001-08-01

Sympathetic nerve activity, including that in the kidney, is increased in heart failure with increased plasma concentrations of norepinephrine and the vasoconstrictor cotransmitter neuropeptide Y (NPY). We examined the contribution of NPY to sympathetically mediated alterations in kidney function in normal and heart failure rats. Heart failure rats were created by left coronary ligation and myocardial infarction. In anesthetized normal rats, the NPY Y(1) receptor antagonist, H 409/22, at two doses, had no effect on heart rate, arterial pressure, or renal hemodynamic and excretory function. In conscious severe heart failure rats, high-dose H 409/22 decreased mean arterial pressure by 8 +/- 2 mm Hg but had no effect in normal and mild heart failure rats. During graded frequency renal sympathetic nerve stimulation (0 to 10 Hz), high-dose H 409/22 attenuated the decreases in renal blood flow only at 10 Hz (-36% +/- 5%, P <.05) in normal rats but did so at both 4 (-29% +/- 4%, P <.05) and 10 Hz (-33% +/- 5%, P <.05) in heart failure rats. The glomerular filtration rate, urinary flow rate, and sodium excretion responses to renal sympathetic nerve stimulation were not affected by high-dose H 409/22 in either normal or heart failure rats. NPY does not participate in the regulation of kidney function and arterial pressure in normal conscious or anesthetized rats. When sympathetic nervous system activity is increased, as in heart failure and intense renal sympathetic nerve stimulation, respectively, a small contribution of NPY to maintenance of arterial pressure and to sympathetic renal vasoconstrictor responses may be identified.

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.

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.

Trigeminal Neuralgia Treated With Stereotactic Radiosurgery: The Effect of Dose Escalation on Pain Control and Treatment Outcomes

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

Kotecha, Rupesh; Kotecha, Ritesh; Modugula, Sujith

Purpose: To analyze the effect of dose escalation on treatment outcome in patients undergoing stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). Methods and Materials: A retrospective review was performed of 870 patients who underwent SRS for a diagnosis of TN from 2 institutions. Patients were typically treated using a single 4-mm isocenter placed at the trigeminal nerve dorsal root entry zone. Patients were divided into groups based on treatment doses: ≤82 Gy (352 patients), 83 to 86 Gy (85 patients), and ≥90 Gy (433 patients). Pain response was classified using a categorical scoring system, with fair or poor pain control representing treatment failure.more » Treatment-related facial numbness was classified using the Barrow Neurological Institute scale. Log-rank tests were performed to test differences in time to pain failure or development of facial numbness for patients treated with different doses. Results: Median age at first pain onset was 63 years, median age at time of SRS was 71 years, and median follow-up was 36.5 months from the time of SRS. A majority of patients (827, 95%) were clinically diagnosed with typical TN. The 4-year rate of excellent to good pain relief was 87% (95% confidence interval 84%-90%). The 4-year rate of pain response was 79%, 82%, and 92% in patients treated to ≤82 Gy, 83 to 86 Gy, and ≥90 Gy, respectively. Patients treated to doses ≤82 Gy had an increased risk of pain failure after SRS, compared with patients treated to ≥90 Gy (hazard ratio 2.0, P=.0007). Rates of treatment-related facial numbness were similar among patients treated to doses ≥83 Gy. Nine patients (1%) were diagnosed with anesthesia dolorosa. Conclusions: Dose escalation for TN to doses >82 Gy is associated with an improvement in response to treatment and duration of pain relief. Patients treated at these doses, however, should be counseled about the increased risk of treatment-related facial numbness.« less

[Effect of long-term intake of Y3+ in drinking water on learning-memeory functions and growth-development of rats].

PubMed

Wu, Min-Yi; Zhang, Ping; Yang, Wei-Dong; Liu, Jie-Sheng

2006-05-01

The aim of this paper was to learn the effect of long-term intake of Y3+ in drinking water on learning-memory function and growth-development of rats. The rats were fed with water dissolved different level Y3+ (0, 0.534, 53.4, 5340 mg/L) for 6 months, pregnant rate, survive rate, bear rate, variety in weight were calculated, the learning-memory function was observed by step-down test. The results showed that a significantly decrease in electric shock period and an increase in incubation period were observed for the low dose group, in contrast, a significantly increase in electric shock period and error times, and an decreases in weight and survive rate were observed for the high dose group. Y3+ in 0.534 mg/L might improve the function of learning and memory in rats, and that Y3+ in 5340mg/L could restrain both the function of learning-memory functions and growth-development in rats.

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

Persistent activation of nuclear factor-kappa B and expression of pro-inflammatory cytokines in bone marrow cells after exposure of mice to protons

NASA Astrophysics Data System (ADS)

Rithidech, Kanokporn; Reungpatthanaphong, Paiboon; Honikel, Louise; Whorton, Elbert

Protons are the most abundant component of solar particle events (SPEs) in space. Information is limited on early-and late-occurring in vivo biological effects of exposure to protons at doses and dose rates that are similar to what astronauts encounter in space. We conducted a study series to fill this knowledge gap. We focused on the biological effects of 100 MeV/n protons, which are one of the most abundant types of protons induced during SPEs. We gave BALB/cJ mice a whole-body exposure to 0.5 or 1.0 Gy of 100 MeV/n protons, delivered at 0.5 or 1.0 cGy/min. These doses and dose rates of protons were selected because they are comparable to those of SPEs taking place in space. For each dose and dose rate of 100 MeV/n protons, mice exposed to 0 Gy of protons served as sham controls. Mice included in this study were also part of a study series conducted to examine the extent and the mechanisms involved in in vivo induction of genomic instability (expressed as late-occurring chromosome instability) by 100 MeV/n protons. Bone marrow (BM) cells were collected from groups of mice for analyses at different times post-exposure, i.e. early time-points (1.5, 3, and 24 hr) and late time-points (1 and 6 months). At each harvest time, there were five mice per treatment group. Several endpoints were used to investigate the biological effects of 100 MeV/n protons in BM cells from irradiated and sham control mice. The scope of this study was to determine the dose-rate effects of 0.5 Gy of 100 MeV/n protons in BM cells on the kinetics of nuclear factor-kappa B (NF-kappa B) activation and the expression of selected NF-kappa B target proteins known to be involved in inflammatory response, i.e. pro-inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6). Significantly high levels (p values ranging from p¡0.01 and p¡0.05) of activated NF-kappa B were observed in BM cells collected from irradiated mice, relative to those obtained from the corresponding sham controls, at all time-points included in the study, regardless of the dose rate of proton-irradiation. However, these increases were more pronounced when the higher dose rate (1.0 cGy/min) was used. The results indicated that NF-kappa B activation in BM cells persisted up to 6 months after exposure of mice to a single dose of 0.5 Gy of 100 MeV/n protons, delivered at the dose rates occurring in space. Further, significantly up-regulated levels of TNF-alpha were detected in BM cells of exposed mice (p values ranging from p¡0.01 and p¡0.05), compared to those in the corresponding sham controls, at all harvest times, in spite of the difference in dose rate of proton-irradiation. However, steady increases in the levels of IL-1 beta and IL-6 in BM cells of exposed mice over the levels in their sham controls across all time-points included in the study were detected only when a dose rate of 1.0 cGy/min was used. In contrast, with a dose rate of 0.5 cGy/min, significantly high expression levels of these two pro-inflammatory cytokines were consistently found in BM cells collected from exposed mice at late time-points only. In summary, our data provide important information for space flight missions because the findings of persistent activation of NF-kappa B and expression of pro-inflammatory cytokines suggest the occurrence of chronic inflammation after exposure of mice to 100 MeV/n protons that, in turn, may have an important impact on health outcome during space flights. Knowledge gained on the NF-kappa B pathway from this study could, therefore, be useful for planning countermeasure strategies to protect astronauts or space travelers in the space environment. Research funded by NASA Grant NNX07AP88G.

TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

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

Orton, C; Borras, C; Carlson, D

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protectionmore » will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how they might be used to address clinically relevant problems. Underlying assumptions and limitations of existing models and their proper application will be discussed. This multidisciplinary educational session combines the fundamentals of radiobiology for radiation therapy and radiation protection with the practical application of biophysical models for treatment planning and evaluation. Learning Objectives: To understand fractionation in teletherapy and dose rate techniques in brachytherapy. To understand how the linear-quadratic models the effect of radiobiological parameters for radiotherapy. To understand the radiobiological basis of radiation protection standards applied to radiotherapy. To distinguish between stochastic effects and tissue reactions. To learn how to apply concepts of biological effective dose and RBE-weighted dose and to incorporate biological factors that alter radiation response. To discuss clinical strategies to increase therapeutic ratio, i.e., maximize local control while minimizing the risk of acute and late normal tissue effects.« less

Effects of β-blockers and anxiety on complication rates after acute myocardial infarction.

PubMed

Abu Ruz, Mohannad E; Lennie, Terry A; Moser, Debra K

2011-01-01

Anxiety is common after acute myocardial infarction and increases the number of complications and the length of stay in the hospital. Anxiety-induced activation of the sympathetic nervous system is hypothesized to be an underlying cause of increased complication rates. Little is known about whether use of β-blockers eliminates the effects of anxiety on complication rate and length of stay. To compare number of complications and length of stay among nonanxious and anxious patients receiving β-blockers during hospitalization. A total of 322 patients with acute myocardial infarction participated in this study within 48 hours of hospital admission. Patients completed the Brief Symptom Inventory to assess anxiety level. After discharge, medical records were reviewed to determine use of β-blockers, type and number of complications, and length of stay. Most patients (96%) were treated with less than 200 mg daily of metoprolol. Anxious patients had more complications (mean [SD], 1.43 [0.15] vs 0.73 [.09], P ≤ .01) and longer stays (7.0 [0.49] vs 5.7 [0.36] days, P < .05) than did nonanxious patients. To test whether the dose of β-blocker made a difference, the interaction between daily dose and anxiety score was tested. No interaction was found between metoprolol dose and anxiety score, and no main effect was found for metoprolol dose. Anxious patients had more complications and longer stays than did nonanxious patients. The administration of metoprolol did not eliminate this relationship, perhaps because patients did not receive a sufficient dose of metoprolol to counter the effect of anxiety.

Dosimetric study of GZP6 60 Co high dose rate brachytherapy source.

PubMed

Lei, Qin; Xu, Anjian; Gou, Chengjun; Wen, Yumei; He, Donglin; Wu, Junxiang; Hou, Qing; Wu, Zhangwen

2018-05-28

The purpose of this study was to obtain dosimetric parameters of GZP6 60 Co brachytherapy source number 3. The Geant4 MC code has been used to obtain the dose rate distribution following the American Association of Physicists in Medicine (AAPM) TG-43U1 dosimetric formalism. In the simulation, the source was centered in a 50 cm radius water phantom. The cylindrical ring voxels were 0.1 mm thick for r ≤ 1 cm, 0.5 mm for 1 cm < r ≤ 5 cm, and 1 mm for r > 5 cm. The kerma-dose approximation was performed for r > 0.75 cm to increase the simulation efficiency. Based on the numerical results, the dosimetric datasets were obtained. These results were compared with the available data of the similar 60 Co high dose rate sources and the detailed dosimetric characterization was discussed. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Effect of different laser irradiation on the dysentery bacilli

NASA Astrophysics Data System (ADS)

Ou, Lin; Chen, Rong; Chen, Yanjiao; Li, Depin; Wen, Caixia

1998-08-01

The S. flexnesi, which have high drug-resistance especially in Cm, Sm, Tc, SD, were irradiated by Ar+ laser at 488 nm and semiconductor laser at 808 nm. The experiment results have shown that both Ar+ laser and semiconductor laser with power density of 1.7 w/cm2 and irradiation dose of 2000 J/cm2 can conduce to the bacterial lethality and increase the mutation rates of the bacterial drug-sensitivity, and 'Colony Count' method have the superiority over the 'Inhibacteria Ring' method. At the mean time it further indicate that the high power semiconductor laser would play an important role in the sciences of laser biological medicine. But the effect of the near infrared semiconductor laser is far lower than that of Ar+ laser of shorter wavelength at the same irradiation dose. It is clear that the output and irradiation dose of near infrared semiconductor laser shall be increased in order to get the same rates of the bacterial lethality and the drug-sensitivity mutation as Ar+ laser's.

Rivaroxaban in patients with a recent acute coronary syndrome.

PubMed

Mega, Jessica L; Braunwald, Eugene; Wiviott, Stephen D; Bassand, Jean-Pierre; Bhatt, Deepak L; Bode, Christoph; Burton, Paul; Cohen, Marc; Cook-Bruns, Nancy; Fox, Keith A A; Goto, Shinya; Murphy, Sabina A; Plotnikov, Alexei N; Schneider, David; Sun, Xiang; Verheugt, Freek W A; Gibson, C Michael

2012-01-05

Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome. In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04). In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).

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

[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.

Low-Dose Radiation Therapy (2 Gy × 2) in the Treatment of Orbital Lymphoma

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

Fasola, Carolina E.; Jones, Jennifer C.; Huang, Derek D.

2013-08-01

Purpose: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). Results: Atmore » a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. Conclusions: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.« less

Effectiveness of using low rate fluoroscopy to reduce an examiner's radiation dose during lumbar nerve root block.

PubMed

Yamane, Kentaro; Kai, Nobuo; Mazaki, Tetsuro; Miyamoto, Tadashi; Matsushita, Tomohiro

2018-06-13

Long-term exposure to radiation can lead to gene mutations and increase the risk of cancer. Low rate fluoroscopy has the potential to reduce the radiation exposure for both the examiner and the patient during various fluoroscopic procedures. The purpose of this study was to evaluate the impact of low rate fluoroscopy on reducing an examiner's radiation dose during nerve root block. A total of 101 lumbar nerve root block examinations were performed at our institute during a 6-month period. During the first 3 months, low rate fluoroscopy was performed at 7.5 frames/s (FPS) in 54 examinations, while 47 were performed at 15 FPS during the last 3 months. The examiner wore a torso protector, a neck protector, radiation protection gloves, and radiation protection glasses. Optically stimulated luminescence (OSL) dosimeter badges were placed on both the inside and the outside of each protector. The dosimeters were exchanged every month. Radiation doses (mSv) were measured as the integrated radiation quantity every month from the OSL dosimeters. The effective and equivalent doses for the hands, skin, and eyes were investigated. The mean monthly equivalent doses were significantly lower both inside and outside the hand protector for the 7.5 FPS versus 15 FPS (inside; P = 0.021, outside; P = 0.024). There were no significant differences between the two groups for the mean monthly calculated effective dose for each protector's condition. Radiation exposure was significantly reduced for the skin on the examiner's hand when using low rate fluoroscopy at 7.5 FPS, with no noticeable decrease in image quality or prolonged fluoroscopy time. Copyright © 2018. Published by Elsevier B.V.

Peri-interventional antibiotic prophylaxis only vs continuous low-dose antibiotic treatment in patients with JJ stents: a prospective randomised trial analysing the effect on urinary tract infections and stent-related symptoms.

PubMed

Moltzahn, Felix; Haeni, Katharina; Birkhäuser, Frédéric D; Roth, Beat; Thalmann, George N; Zehnder, Pascal

2013-02-01

To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial. In all, 95 patients were randomised to either receive peri-interventional antibiotic prophylaxis during stent insertion only (group A, 44 patients) or to additionally receive a continuous low-dose antibiotic treatment until stent removal (group B, 51). Evaluations for urinary tract infections (UTI), stent-related symptoms (SRSs) and drug side-effects were performed before stent insertion and consecutively after 1, 2 and 4 weeks and/or at stent withdrawal. All patients received a peri-interventional antibiotic prophylaxis with 1.2 g amoxicillin/clavulanic acid. Amoxicillin/clavulanic acid (625 mg) once daily was administered for continuous low-dose treatment (group B). Primary endpoints were the overall rates of UTIs and SRSs. Secondary endpoints were the rates and severity of drug side-effects. Neither the overall UTI rates (group A: 9% vs group B: 10%), nor the rates of febrile UTIs (group A: 7% vs group B: 6%) were different between the groups. Similarly, SRS rates did not differ (group A: 98% vs group B: 96%). Antibiotic side-effect symptoms were to be increased in patients treated with low-dose antibiotics. A continuous antibiotic low-dose treatment during the entire JJ stent-indwelling time does not reduce the quantity or severity of UTIs and has no effect on SRSs either compared with a peri-interventional antibiotic prophylaxis only. © 2012 BJU International.

High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors.

PubMed

Timmermand, Oskar V; Nilsson, Jenny; Strand, Sven-Erik; Elgqvist, Jörgen

2016-12-01

The first main aim of this study was to illustrate the absorbed dose rate distribution from 177 Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90 Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using 177 Lu-h11B6, directed against the human kallikrein 2 antigen. Male immunodeficient BALB/c nude mice, aged 6-8 w, were inoculated by subcutaneous injection of ∼10 7 LNCaP cells in a 200 μl suspension of a 1:1 mixture of medium and Matrigel. The antibody h11B6 was conjugated with the chelator CHX-A″-DTPA after which conjugated h11B6 was mixed with 177 LuCl 3 . The incubation was performed at room temperature for 2 h, after which the labeling was terminated and the solution was purified on a NAP-5 column. About 20 MBq 177 Lu-h11B6 was injected intravenously in the tail vein. At approximately 10 h postinjection (hpi), the mice were sacrificed and one tumor was collected from each of the five animals and cryosectioned into 10 μm thick slices. The tumor slices were measured and imaged using the DAR MicroImager system and the M3Vision software. Then the absorbed dose rate was calculated using a dose point kernel generated with the Monte Carlo code gate v7.0. The DAR system produced high resolution images of the radioactivity distribution, close to the resolution of single PCa cells. The DAR images revealed a pronounced heterogeneous radioactivity distribution, i.e., count rate per area, in the tumors, indicated by the normalized intensity variations along cross sections as mean ± SD: 0.15 ± 0.15, 0.20 ± 0.18, 0.12 ± 0.17, 0.15 ± 0.16, and 0.23 ± 0.22, for each tumor section, respectively. The absorbed dose rate distribution for 177 Lu at the time of dissection 10 hpi showed a maximum value of 2.9 ± 0.4 Gy/h (mean ± SD), compared to 6.0 ± 0.9 and 159 ± 25 Gy/h for the hypothetical 90 Y and 7 MeV alpha-particle cases assuming the same count rate densities. Mean absorbed dose rate values were 0.13, 0.53, and 6.43 Gy/h for 177 Lu, 90 Y, and alpha-particles, respectively. The initial uptake of 177 Lu-h11B6 produces a high absorbed dose rate, which is important for a successful therapeutic outcome. The hypothetical 90 Y case indicates a less heterogeneous absorbed dose rate distribution and a higher mean absorbed dose rate compared to 177 Lu, although with a potentially increased irradiation of surrounding healthy tissue. The hypothetical alpha-particle case indicates the possibility of a higher maximum absorbed dose rate, although with a more heterogeneous absorbed dose rate distribution.

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.

Comparison of particulate matter dose and acute heart rate variability response in cyclists, pedestrians, bus and train passengers.

PubMed

Nyhan, Marguerite; McNabola, Aonghus; Misstear, Bruce

2014-01-15

Exposure to airborne particulate matter (PM) has been linked to cardiovascular morbidity and mortality. Heart rate variability (HRV) is a measure of the change in cardiac autonomic function, and consistent links between PM exposure and decreased HRV have been documented in studies. This study quantitatively assesses the acute relative variation of HRV with predicted PM dose in the lungs of commuters. Personal PM exposure, HR and HRV were monitored in 32 young healthy cyclists, pedestrians, bus and train passengers. Inhaled and lung deposited PM doses were determined using a numerical model of the human respiratory tract which accounted for varying ventilation rates between subjects and during commutes. Linear mixed models were used to examine air pollution dose and HRV response relationships in 122 commutes sampled. Elevated PM2.5 and PM10 inhaled and lung deposited doses were significantly (p<0.05) associated with decreased HRV indices. Percent declines in SDNN (standard deviation of normal RR intervals) relative to resting, due to an inter-quartile range increase in PM10 lung deposited dose were stronger in cyclists (-6.4%, 95% CI: -11.7, -1.3) and pedestrians (-5.8%, 95% CI: -11.3, -0.5), in comparison to bus (-3.2%, 95% CI: -6.4, -0.1) and train (-1.8%, -7.5, 3.8) passengers. A similar trend was observed in the case of PM2.5 lung deposited dose and results for rMSSD (the square root of the squared differences of successive normal RR intervals) followed similar trends to SDNN. Inhaled and lung deposited doses accounting for varying ventilation rates between modes, individuals and during commutes have been neglected in other studies relating PM to HRV. The findings here indicate that exercise whilst commuting has an influence on inhaled PM and PM lung deposited dose, and these were significantly associated with acute declines in HRV, especially in pedestrians and cyclists. © 2013.

Thalidomide treatment in cutaneous lesions of systemic lupus erythematosus: a multicenter study in China.

PubMed

Wang, Dandan; Chen, Haifeng; Wang, Shiying; Zou, Yaohong; Li, Jing; Pan, Jieping; Wang, Xiangdang; Ren, Tianli; Zhang, Yu; Chen, Zhiwei; Feng, Xuebing; Sun, Lingyun

2016-06-01

Thalidomide is effective for treating severe cutaneous lupus patients. The aim of this study was to observe the optimum effective and maintenance doses of thalidomide to maximize clinical benefit and minimize side effects for patients with cutaneous lupus in China. Sixty-nine patients with lupus rash from eight hospitals in China were enrolled and treated with different doses of thalidomide. We started the dose of thalidomide at 25 mg daily and gradually increased administration dose once a week until erythema was markedly improved. The effective and maintenance doses were documented. The size of skin lesions was noted once a week. Systemic lupus erythematosus disease activity index (SLEDAI) score, levels of erythrocyte sedimentation rate (ESR), and serum TNF-α were measured before and after treatment. The remission rates were evaluated weekly until 8 weeks. Sixty-eight percent of patients showed an effective dose of 50 mg daily; another 13, 10, and 9 % of patients had an effective dose of 100, 75, and 25 mg daily, respectively. The maintenance dose was 50 mg daily for 71 % of the patients, and 100, 75, and 25 mg daily for 9, 14, and 6 % of the patients. SLEDAI score and serum ESR levels significantly decreased 4 weeks after thalidomide treatment. At the end of the fourth week, the rates of complete remission, partial remission, and no response were 56 % (n = 39), 41 % (n = 28), and 3 % (n = 2). At the eighth week, the rate of total remission rose up to 100 %. The most common side effects were drowsiness and constipation. No peripheral neuropathy was observed in these patients. Thalidomide at a dose of 50 mg daily may offer a better benefit to risk ratio in the treatment of Chinese cutaneous lupus patients.

Treatment Sequencing for Childhood ADHD: A Multiple-Randomization Study of Adaptive Medication and Behavioral Interventions.

PubMed

Pelham, William E; Fabiano, Gregory A; Waxmonsky, James G; Greiner, Andrew R; Gnagy, Elizabeth M; Pelham, William E; Coxe, Stefany; Verley, Jessica; Bhatia, Ira; Hart, Katie; Karch, Kathryn; Konijnendijk, Evelien; Tresco, Katy; Nahum-Shani, Inbal; Murphy, Susan A

2016-01-01

Behavioral and pharmacological treatments for children with attention deficit/hyperactivity disorder (ADHD) were evaluated to address whether endpoint outcomes are better depending on which treatment is initiated first and, in case of insufficient response to initial treatment, whether increasing dose of initial treatment or adding the other treatment modality is superior. Children with ADHD (ages 5-12, N = 146, 76% male) were treated for 1 school year. Children were randomized to initiate treatment with low doses of either (a) behavioral parent training (8 group sessions) and brief teacher consultation to establish a Daily Report Card or (b) extended-release methylphenidate (equivalent to .15 mg/kg/dose bid). After 8 weeks or at later monthly intervals as necessary, insufficient responders were rerandomized to secondary interventions that either increased the dose/intensity of the initial treatment or added the other treatment modality, with adaptive adjustments monthly as needed to these secondary treatments. The group beginning with behavioral treatment displayed significantly lower rates of observed classroom rule violations (the primary outcome) at study endpoint and tended to have fewer out-of-class disciplinary events. Further, adding medication secondary to initial behavior modification resulted in better outcomes on the primary outcomes and parent/teacher ratings of oppositional behavior than adding behavior modification to initial medication. Normalization rates on teacher and parent ratings were generally high. Parents who began treatment with behavioral parent training had substantially better attendance than those assigned to receive training following medication. Beginning treatment with behavioral intervention produced better outcomes overall than beginning treatment with medication.

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.

Comparative toxicity and micronuclei formation in Tribolium castaneum, Callosobruchus maculatus and Sitophilus oryzae exposed to high doses of gamma radiation.

PubMed

Ahmadi, Mehrdad; Mozdarani, Hossein; Abd-Alla, Adly M M

2015-07-01

The effects of gamma radiation on mortality and micronucleus formation in Tribolium castaneum Herbst, Callosobruchus maculatus (F.) and Sitophilus oryzae (L.) genital cells were evaluated. Two groups of healthy and active adult insects 1-3 and 8-10 days old were irradiated with various doses (50-200 Gy) gamma ray. Seven days post-irradiation; mortality rates and micronucleus formation were assessed in genital cells of the irradiated insects. The results show that with increasing gamma doses, the mortality rate of each species increased and T. castaneum and S. oryzae showed the low and high sensitivity respectively. It was shown that the micronucleus appearance in the tested insects had correlation with amount and intensity of radiation doses. Moreover our results indicate different levels in the genotoxicity of gamma radiation among the insects' genital cells under study. The frequency of micronuclei in genital cells of 1-3 days old insects exposed to 50 and 200 Gy were 12.6 and 38.8 Mn/1000 cells in T. castaneum, 20.8 and 46.8 Mn/1000 cells in C. maculatus and 16.8 and 57.2 Mn/1000 cells in S. oryzae respectively. A high sensitivity of the genital cells to irradiation exposure was seen in S. oryzae correlated with its high mortality rate compared with the other two species. These results might be indicative of inflicting chromosomal damage expressed as micronucleus in high mortality rates observed in the pest population; an indication of genotoxic effects of radiation on the studied species. Copyright © 2015 Elsevier Ltd. All rights reserved.

30 CFR 62.101 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 85 dBA, or equivalently a dose of 50%, integrating all sound levels from 80 dBA to at least 130 dBA... Protection Level. A TWA8 of 105 dBA, or equivalently, a dose of 800% of that permitted by the standard, integrating all sound levels from 90 dBA to at least 140 dBA. Exchange rate. The amount of increase in sound...

30 CFR 62.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 85 dBA, or equivalently a dose of 50%, integrating all sound levels from 80 dBA to at least 130 dBA... Protection Level. A TWA8 of 105 dBA, or equivalently, a dose of 800% of that permitted by the standard, integrating all sound levels from 90 dBA to at least 140 dBA. Exchange rate. The amount of increase in sound...

Design of a boron neutron capture enhanced fast neutron therapy assembly

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

Wang, Zhonglu

The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator nearmore » the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm 2 treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm 2 collimation was 21.9% per 100-ppm 10B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm 2 fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm 2 collimator. Five 1.0-cm thick 20x20 cm 2 tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm 10B) to measure dose due to boron neutron capture. The measured dose enhancement at 5.0-cm depth in the head phantom for the 5.0-cm thick tungsten filter is (16.6 ± 1.8)%, which agrees well with the MCNP simulation of the simplified BNCEFNT assembly, (16.4 ± 0.5)%. The error in the calculated dose enhancement only considers the statistical uncertainties. The total dose rate measured at 5.0-cm depth using the non-borated ion chamber is (0.765 ± 0.076) Gy/MU, about 61% of the fast neutron standard dose rate (1.255Gy/MU) at 5.0-cm depth for the standard 10x10 cm 2 treatment beam. The increased doses to other organs due to the use of the BNCEFNT assembly were calculated using MCNP5 and a MIRD phantom. The activities of the activation products produced in the BNCEFNT assembly after neutron beam delivery were computed. The photon ambient dose rate due to the radioactive activation products was also estimated.« less

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

PubMed

Lensen, Sarah F; Wilkinson, Jack; Leijdekkers, Jori A; La Marca, Antonio; Mol, Ben Willem J; Marjoribanks, Jane; Torrance, Helen; Broekmans, Frank J

2018-02-01

During a cycle of in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. Generally, the dose of FSH is associated with the number of eggs retrieved. A normal response to stimulation is often considered desirable, for example the retrieval of 5 to 15 oocytes. Both poor and hyper-response are associated with increased chance of cycle cancellation. Hyper-response is also associated with increased risk of ovarian hyperstimulation syndrome (OHSS). Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response such as age. More recently, clinicians have begun using ovarian reserve tests (ORTs) to predict ovarian response based on the measurement of various biomarkers, including basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose based on these markers improves clinical outcomes. To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, LILACS, DARE, ISI Web of Knowledge, ClinicalTrials.gov, and the World Health Organisation International Trials Registry Platform search portal from inception to 27th July 2017. We checked the reference lists of relevant reviews and included studies. We included trials that compared different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal or high responders based on AMH, AFC, and/or bFSH) and trials that compared an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. Secondary outcomes included clinical pregnancy, moderate or severe OHSS, multiple pregnancy, oocyte yield, cycle cancellations, and total dose and duration of FSH administration. We included 20 trials (N = 6088); however, we treated those trials with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence quality ranged from very low to moderate. The main limitations were imprecision and risk of bias associated with lack of blinding.Direct dose comparisons in women according to predicted responseAll evidence was low or very low quality.Due to differences in dose comparisons, caution is warranted in interpreting the findings of five small trials assessing predicted low responders. The effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy.Similarly, in predicted normal responders (nine studies, three comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units: OR 0.88, 95% CI 0.57 to 1.36; N = 522; 2 studies; I 2 = 0%) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the outcome of OHSS to enable any inferences.In predicted high responders, lower doses may or may not have an impact on rates of live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; N = 521; 1 study), OHSS, and clinical pregnancy. However, lower doses probably reduce the likelihood of moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; N = 521; 1 study).ORT-algorithm studiesFour trials compared an ORT-based algorithm to a non-ORT control group. Rates of live birth/ongoing pregnancy and clinical pregnancy did not appear to differ by more than a few percentage points (respectively: OR 1.04, 95% CI 0.88 to 1.23; N = 2823, 4 studies; I 2 = 34%; OR 0.96, 95% CI 0.82 to 1.13, 4 studies, I 2 =0%, moderate-quality evidence). However, ORT algorithms probably reduce the likelihood of moderate or severe OHSS (Peto OR 0.58, 95% CI 0.34 to 1.00; N = 2823; 4 studies; I 2 = 0%, low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.54, 95% CI 0.14 to 1.99; N = 1494; 3 studies; I 2 = 0%, low quality evidence). Our findings suggest that if the chance of live birth with a standard dose is 26%, the chance with ORT-based dosing would be between 24% and 30%. If the chance of moderate or severe OHSS with a standard dose is 2.5%, the chance with ORT-based dosing would be between 0.8% and 2.5%. These results should be treated cautiously due to heterogeneity in the study designs. We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT), influenced rates of live birth/ongoing pregnancy but we could not rule out differences, due to sample size limitations. In predicted high responders, lower doses of FSH seemed to reduce the overall incidence of moderate and severe OHSS. Moderate-quality evidence suggests that ORT-based individualisation produces similar live birth/ongoing pregnancy rates to a policy of giving all women 150 IU. However, in all cases the confidence intervals are consistent with an increase or decrease in the rate of around five percentage points with ORT-based dosing (e.g. from 25% to 20% or 30%). Although small, a difference of this magnitude could be important to many women. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU, probably by facilitating dose reductions in women with a predicted high response. However, the size of the effect is unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates, and many of the included studies had a serious risk of bias.Current evidence does not provide a clear justification for adjusting the standard dose of 150 IU in the case of poor or normal responders, especially as increased dose is generally associated with greater total FSH dose and therefore greater cost. However, a decreased dose in predicted high responders may reduce OHSS.

Efficacy of Praziquantel against Schistosoma mekongi and Opisthorchis viverrini: A Randomized, Single-Blinded Dose-Comparison Trial

PubMed Central

Phongluxa, Khampheng; Ayé Soukhathammavong, Phonepasong; Vonghachack, Youthanavanh; Keiser, Jennifer; Vounatsou, Penelope; Tanner, Marcel; Hatz, Christoph; Utzinger, Jürg; Odermatt, Peter; Akkhavong, Kongsap

2012-01-01

Background Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ) is the drug of choice for morbidity control but few dose comparisons have been made. Methodology Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz) before and 28–30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45) or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45). Adverse events were assessed at 3 and 24 hours posttreatment. Principal Findings Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI): 56.6–88.5%) and 80.8% (95% CI: 60.6–93.4%) for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60). O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4–84.4%) and 96.6% (95% CI: not defined), respectively (P = 0.009). Egg reduction rates (ERRs) against O. viverrini were very high for both doses (>99%), but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1%) and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment). Adverse events were common (96%), mainly mild with no significant differences between the two treatment groups. Conclusions/Significance Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. Trial Registration Controlled-Trials.com ISRCTN57714676 PMID:22848766

Comparison of effects produced by nicotine and the α4β2-selective agonist 5-I-A-85380 on intracranial self-stimulation in rats.

PubMed

Freitas, Kelen; Carroll, F Ivy; Negus, S Stevens

2016-02-01

Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets, including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the nonselective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or "facilitation") of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-β-erythroidine (DHβE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain-stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHβE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PsycINFO Database Record (c) 2016 APA, all rights reserved.

Calculating evidence-based renal replacement therapy - Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy - A before and after study.

PubMed

Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

2016-02-01

Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given "dose" can be difficult. In research, the "dose" of renal replacement therapy is given as effluent flow rate in ml kg -1  h -1 . Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses of renal replacement therapy. Our aim was to design an excel calculator which would personalise patient's treatment, deliver an effective, evidence-based dose of renal replacement therapy without large variations in practice and prolong filter life. Our calculator prescribes a haemodialfiltration dose of 25 ml kg -1  h -1 whilst limiting the filtration fraction to 15%. We compared the episodes of renal replacement therapy received by a historical group of patients, by retrieving their data stored on the haemofiltration machines, to a group where the calculator was used. In the second group, the data were gathered prospectively. The median delivered dose reduced from 41.0 ml kg -1  h -1 to 26.8 ml kg -1  h -1 with reduced variability that was significantly closer to the aim of 25 ml kg -1 .h -1 ( p  < 0.0001). The median treatment time increased from 8.5 h to 22.2 h ( p  = 0.00001). Our calculator significantly reduces variation in prescriptions of continuous veno-venous haemodiafiltration and provides an evidence-based dose. It is easy to use and provides personal care for patients whilst optimizing continuous veno-venous haemodiafiltration delivery and treatment times.

Gamma-ray spectra and doses from the Little Boy replica

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

Moss, C.E.; Lucas, M.C.; Tisinger, E.W.

1984-01-01

Most radiation safety guidelines in the nuclear industry are based on the data concerning the survivors of the nuclear explosions at Hiroshima and Nagasaki. Crucial to determining these guidelines is the radiation from the explosions. We have measured gamma-ray pulse-height distributions from an accurate replica of the Little Boy device used at Hiroshima, operated at low power levels near critical. The device was placed outdoors on a stand 4 m from the ground to minimize environmental effects. The power levels were based on a monitor detector calibrated very carefully in independent experiments. High-resolution pulse-height distributions were acquired with a germaniummore » detector to identify the lines and to obtain line intensities. The 7631 to 7645 keV doublet from neutron capture in the heavy steel case was dominant. Low-resolution pulse-height distributions were acquired with bismuth-germanate detectors. We calculated flux spectra from these distributions using accurately measured detector response functions and efficiency curves. We then calculated dose-rate spectra from the flux spectra using a flux-to-dose-rate conversion procedure. The integral of each dose-rate spectrum gave an integral dose rate. The integral doses at 2 m ranged from 0.46 to 1.03 mrem per 10/sup 13/ fissions. The output of the Little Boy replica can be calculated with Monte Carlo codes. Comparison of our experimental spectra, line intensities, and integral doses can be used to verify these calculations at low power levels and give increased confidence to the calculated values from the explosion at Hiroshima. These calculations then can be used to establish better radiation safety guidelines. 7 references, 7 figures, 2 tables.« less

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

PubMed

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

Radiation of Bactrocera dorsalis (Diptera: Tephritidae) Eggs to Improve the Mass Rearing of Diachasmimorpha longicaudata (Hymenoptera: Braconidae).

PubMed

Cai, Pumo; Hong, Jingfang; Wang, Cong; Yang, Yanchuan; Zhang, Qiwen; Ji, Qinge; Chen, Jiahua

2018-05-28

This study explored the potential for Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) larvae hatched from irradiated eggs as hosts for Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae). B. dorsalis eggs of three different ages (12-, 24-, and 36-h old) were analyzed for hatchability, pupation rate, pupal weight, emergence rate, and sex ratio after exposure to different doses of radiation (5 and 10 Gy) at different dose rates (1 and 6 Gy/min). For the eggs of different ages exposed to radiation, only the hatchability and pupal weight of 36-h-old eggs exposed to the dose rate of 1 Gy/min were not affected; therefore, 6 Gy/min was not suitable for irradiating eggs. The viability of the parents and progenies of D. longicaudata when the parents were reared from 36-h-old eggs irradiated at nine different doses (0, 5, 10, 15, 20, 25, 30, 35, and 40 Gy) under laboratory conditions were investigated. The emergence percentage, sex ratio, and longevity of parasitoids developed from irradiated eggs were similar to those reared from nonirradiated hosts. A significant increase in larva mortality was observed for the eggs irradiated at doses above 25 Gy, and no redundant adult flies emerged at doses above 15 Gy. Hence, for B. dorsalis eggs to be applied in the mass rearing of D. longicaudata, the age of 36 h and a dose of 20-25 Gy are the optimal parameters. The results reveal that hosts and parasitoids need not be separated, enabling a reduction in cost, labor, and time and resulting in an improved mass rearing procedure for D. longicaudata.

TU-CD-304-04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

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

Yi, B; Xu, H; Mutaf, Y

2015-06-15

Purpose: Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI. Methods: Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speedmore » of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements. Results: Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity-oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min. Conclusion: This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC-based thickness compensation and partial lung blocking are also possible.« less

Comparison of two neonatal indomethacin protocols: efficacy and outcome for patent ductus arteriosus closure.

PubMed

Rosito, G; Sum, K; Chorne, N

2010-10-01

Indomethacin, a non-selective inhibitor of prostaglandin synthesis, is the gold standard treatment for patent ductus arteriosus (PDA). Indomethacin has been shown to permanently close the ductus and when given prophylactically, it reduces the incidence of PDA (1, 2). This study compares PDA closure and surgical ligation rates between patients using two different indomethacin administration protocols. This is a retrospective comparison analysis of 72 neonates, who received one of two indomethacin administration protocols. Our previous protocol suggested an initial dose of 0·2 mg/kg followed by two 0·1 mg/kg, with doses infused over 4 h and a 24-h dosing interval. A new potentially more useful protocol using the same mg/kg dose regimen but with doses infused over 30 min and a 12-h dosing interval, was evaluated. Each neonate was allowed three courses of treatment before surgical ligation was performed for persistent PDA. There were no statistically significant differences between the two protocol groups when comparing percentages of neonates with gestational age≤28 weeks, birth weight≤1000 g, male gender or receiving indomethacin for the indication of PDA prophylaxis vs. treatment. There was a trend towards a higher PDA closure rate and subsequently a lower PDA ligation rate in the new protocol when compared with the previous protocol. In this small population of premature neonates, there was a trend, but no significant difference, towards increasing PDA closure and lower surgical ligation rates in neonates given indomethacin with more frequent dosing and shorter infusion time. A well-powered randomized controlled trial is now needed. Copyright © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ) radiation.

PubMed

Kumarathasan, Prem; Vincent, Renaud; Blais, Erica; Saravanamuthu, Anu; Gupta, Pallavi; Wyatt, Heather; Mitchel, Ronald; Hannan, Mohammed; Trivedi, Akilesh; Whitman, Stewart

2013-01-01

There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation. B6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body) to Co60 (γ) (single dose 0, 0.5, and 2 Gy) at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy) at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3-6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05) in a dose-dependent manner 3-6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05) after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008) relative to controls. Percent lesion area increased (p = 0.005) with age of animal, but not with radiation treatment. Our observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE-/- mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.

Dissipation and adsorption of isoproturon, tebuconazole, chlorpyrifos and their main transformation products under laboratory and field conditions.

PubMed

Papadopoulou, Evangelia S; Karas, Panagiotis A; Nikolaki, Sofia; Storck, Veronika; Ferrari, Federico; Trevisan, Marco; Tsiamis, George; Martin-Laurent, Fabrice; Karpouzas, Dimitrios G

2016-11-01

Assessment of dissipation constitutes an integral part of pesticides risk assessment since it provides an estimate of the level and the duration of exposure of the terrestrial ecosystem to pesticides. Within the frame of an overall assessment of the soil microbial toxicity of pesticides, we investigated the dissipation of a range of dose rates of three model pesticides, isoproturon (IPU), tebuconazole (TCZ), and chlorpyrifos (CHL), and the formation and dissipation of their main transformation products following a tiered lab-to-field approach. The adsorption of pesticides and their transformation products was also determined. IPU was the least persistent pesticide showing a dose-dependent increase in its persistence in both laboratory and field studies. CHL dissipation showed a dose-dependent increase under laboratory conditions and an exact opposite trend in the field. TCZ was the most persistent pesticide under lab conditions showing a dose-dependent decrease in its dissipation, whereas in the field TCZ exhibited a biphasic dissipation pattern with extrapolated DT90s ranging from 198 to 603.4days in the ×1 and ×2 dose rates, respectively. IPU was demethylated to mono- (MD-IPU) and di-desmethyl-isoproturon (DD-IPU) which dissipated following a similar pattern with the parent compound. CHL was hydrolyzed to 3,5,6-trichloro-2-pyridinol (TCP) which dissipated showing a reverse dose-dependent pattern compared to CHL. Pesticides adsorption affinity increased in the order IPU

Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

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

Neelis, Karen J.; Schimmel, Erik C.; Vermeer, Maarten H.

Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of themore » 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.« less

Flavor improvement does not increase abuse liability of nicotine chewing gum.

PubMed

Houtsmuller, Elisabeth J; Fant, Reginald V; Eissenberg, Thomas E; Henningfield, Jack E; Stitzer, Maxine L

2002-06-01

Because the taste of nicotine gum has impeded compliance with dosing recommendations, nicotine gum with improved taste (mint, orange) was developed and marketed. Prior to marketing, the Food and Drug Administration (FDA) required a rigorous abuse liability assessment to examine whether enhanced palatability of nicotine gum would increase its abuse liability. Subjective, physiological, and psychomotor effects of mint flavor and original nicotine gum were tested in adult smokers (22-55 years old); a group of younger subjects (18-21 years old) was also included to allow for assessment of abuse liability in young adults specifically. Amphetamine and confectionery gum served as positive controls for abuse liability and palatability. Subjects rated palatability of mint gum higher than original nicotine gum, but substantially lower than confectionery gum. Palatability decreased with increasing dose of nicotine. Neither original nor mint gum increased ratings of traditional abuse liability predictors [Good Effect, Like Effect, Morphine-Benzedrine Group (MBG) scales of Addiction Research Center Inventory (ARCI)], while amphetamine increased ratings of all these measures. Both flavors of nicotine gum decreased craving during 2 h of abstinence. These effects were more pronounced in the adult group and mint gum was more effective than original gum. Younger subjects reported fewer withdrawal symptoms and lower ratings for drug effects and flavor. Improved flavor of nicotine gum does not increase abuse liability, but may be associated with enhanced craving reduction.

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).

The predictive factors of α1-D/A adrenoceptor antagonist, naftopidil, dose increase therapy for male lower urinary tract symptoms caused by benign prostatic hyperplasia: INFORM study.

PubMed

Tanuma, Yasushi; Tanaka, Yoshinori; Takeyama, Ko; Okamoto, Tomoshi

2017-01-01

We evaluated the predictive factors which affect the efficacy of naftopidil 50 mg/day therapy and dose increase therapy to administration of 75 mg/day after an initial dose of 50 mg/day. A total of 92 patients with male lower urinary tract symptoms/benign prostatic hyperplasia were administrated naftopidil 50 mg/day for 4 weeks (50 mg therapy). At week 4, the patients were divided into an effective and an ineffective group (Group E and Group I, respectively). For further 4 weeks, the dosage of naftopidil was increased to 75 mg/day in all patients. At week 8, the patients of Group E and Group I were divided into an effective and an ineffective group (Group EE, Group EI, Group IE, and Group II, respectively). Postvoid residual (PVR) urine volume at baseline was a predictive factor for efficacy of 50 mg therapy. In Group E, change in International Prostate Symptom Score storage symptoms subscore from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. In Group I, change in maximum flow rate from baseline to week 4 was a predictive factor for efficacy of this dose increase therapy. The short term of naftopidil 50 mg therapy was ineffective for the patients who had large PVR. The predictive factor of this dose increase therapy might be a dynamic variable in 50 mg/day of dose period, but not a baseline variable at the time of 75 mg/day dosage starts.

Single dosing comparison of the relative cardiac beta 1/beta 2 activity of inhaled fenoterol and salbutamol in normal subjects.

PubMed Central

Newnham, D M; Wheeldon, N M; Lipworth, B J; McDevitt, D G

1993-01-01

BACKGROUND--The aim of the present study was to compare the dose related effects of fenoterol and salbutamol on cardiac beta 1 and beta 2 receptors using the beta 1 selective antagonist atenolol, in order to dissect out relative beta 1/beta 2 mediated responses. METHODS--Fourteen normal volunteers were randomised to receive pretreatment with either atenolol 25 mg or placebo, followed by inhaled fenoterol or salbutamol in equal doses by weight (cumulative doses of 1 mg and 4 mg). Measurements were made 30 minutes after inhaling each dose of beta 2 agonist. Values (mean and 95% CI) were expressed as a change from baseline. RESULTS--At 4 mg fenoterol produced equivalent falls in serum potassium and increases in tremor to salbutamol. The mean (95% CI) increase in heart rate (beats/min) with fenoterol at 4 mg after placebo was 47 (41-53) and after atenolol was 34 (28-40), with values for salbutamol being 46 (40-52) after placebo and 30 (24-36) after atenolol. The inotropic response (stroke distance) after atenolol at the 4 mg dose was 5.0 (3.9-6.1) cm for fenoterol and 4.7 (3.5-5.9) cm for salbutamol. There were no significant differences in heart rate or stroke distance response between the two drugs after either placebo or atenolol. Furthermore, ECG effects (Q-Tc and T wave) of fenoterol and salbutamol were comparable at both doses. CONCLUSIONS--These results show that there is no difference in the respective chronotropic or inotropic activities of fenoterol and salbutamol on cardiac beta 1 or beta 2 receptors when given at higher than conventional doses. PMID:8102213

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.

Ultraviolet-B radiation increases serum 25-hydroxyvitamin D levels: the effect of UVB dose and skin color.

PubMed

Armas, Laura A G; Dowell, Susan; Akhter, Mohammed; Duthuluru, Sowjanya; Huerter, Christopher; Hollis, Bruce W; Lund, Richard; Heaney, Robert P

2007-10-01

Ultraviolet (UV)-B light increases vitamin D levels, but the dose response and the effect of skin pigmentation have not been well characterized. We sought to define the relationship between UVB exposure and 25-hydroxyvitamin D (25-OH-D) concentrations as a function of skin pigmentation. Seventy two participants with various skin tones had 90% of their skin exposed to UVB light (20-80 mJ/cm2) 3 times a week for 4 weeks. Serum 25-OH-D was measured weekly. Eighty percent of the variation in treatment response was explained by UVB dose and skin tone. Therapeutically important changes in 25-OH-D were achieved with minimal tanning. Four weeks was not long enough to reach a steady state at the higher dose rates. The response of 25-OH-D levels to UVB light is dependent on skin pigmentation and the amount of UVB given, and useful increases in vitamin D status can be achieved by defined UVB doses small enough to produce only minimal tanning.

Nicorandil, a new vasodilator drug, in patients with essential hypertension.

PubMed

Leonetti, G; Fruscio, M; Gradnik, R; Chianca, R; Bolla, G B; Prandi, P; Zanchetti, A

1989-12-01

In 12 mild to moderate hypertensive patients we investigated the acute antihypertensive efficacy of three different doses of nicorandil, a new vasodilating agent which probably acts by increasing the potassium efflux from smooth muscle cells and causing a cellular hyperpolarization. After a 3-day placebo period the patients were given, according to a double-blind Latin-square randomized design, 10, 20 and 30 mg nicorandil as a single acute dose every other day. Blood pressure and the heart rate were measured in both supine and upright positions at various times for 24 h after the dosing; fractional urine collections were obtained at the end of the placebo period and after each active dose. All doses of nicorandil similarly and significantly (P less than 0.01) reduced supine blood pressure, with a peak after 4-6 h (10 mg: -21/-8 mmHg; 20 mg: -20/-9 mmHg; 30 mg: -29/-17 mmHg), and the effect was still present, though reduced, after 24 h; no change in the heart rate was observed. The results from the upright position were similar. There were no significant changes in urine volume and electrolyte excretion during the nicorandil administration. The three different doses of nicorandil caused similar acute blood pressure reductions without change in the heart rate, nor in the urine volume and urinary sodium.

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.

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)

Effects of a Multi-Ingredient Energy Supplement on Cognitive Performance and Cerebral-Cortical Activation.

PubMed

Daou, Marcos; Sassi, Julia Montagner; Miller, Matthew W; Gonzalez, Adam M

2018-03-13

This study assessed whether a multi-ingredient energy supplement (MIES) could enhance cerebral-cortical activation and cognitive performance during an attention-switching task. Cerebral-cortical activation was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via electroencephalography (EEG) both at rest and during the attention-switching task before (pretest) and 30 min after (posttest) consumption of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or a placebo (PL) in a double-blinded, randomized crossover experimental design. EEG upper-alpha power was assessed at rest and during the task, wherein d' (Z[hit rate]-Z[false alarm rate]) and median reaction time (RT) for correct responses to targets on attention-hold and attention-switch trials were analyzed. For both d' and RT, the Session (MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached statistical significance (p = .07, η 2 p = 0.106). Exploring these interactions with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (ps ≤.034), suggesting the pretest-to-posttest improvement in sensitivity to task target stimuli (d') and RT increased as a function of supplement dose. With respect to upper-alpha power, the Session × Time interaction was significant (p < .001, η 2 p = 0.422). Exploring this interaction with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (p < .001), suggesting pretest-to-posttest increases in cerebral-cortical activation were a function of supplement dose. In conclusion, our findings suggest that MIES can increase cerebral-cortical activation and RT during task performance while increasing sensitivity to target stimuli in a dose-dependent manner.

A protective role of HSP90 chaperone in gamma-irradiated Arabidopsis thaliana seeds

NASA Astrophysics Data System (ADS)

Kozeko, Liudmyla; Talalaiev, Oleksandr; Neimash, Volodymyr; Povarchuk, Vasyl

2015-07-01

The heat shock protein 90 (HSP90) is required for the maturation and conformational regulation of many regulatory proteins affecting morphogenetic pathways and stress tolerance. The purpose of this work is to disclose a role of HSP90 in radioresistance of seeds. Arabidopsis thaliana (Ler) seeds were exposed to γ-ray irradiation with doses of 0.1-1 kGy using 60Co source to obtain a viable but polymorphic material. A comet assay of the seeds showed a dose-dependent increase in DNA damage. Phenotypic consequences of irradiation included growth stimulation at doses of 0.1-0.25 kGy and negative growth effects at doses from 0.5 kGy and beyond, along with increasing heterogeneity of seedling growth rate and phenotype. The frequencies of abnormal phenotypes were highly correlated with the degree of DNA damage in seeds. Treatment of seeds with geldanamycin (GDA), an inhibitor of HSP90, stimulated the seedling growth at all radiation doses and, at the same time, enhanced the growth rate and morphological diversity. It was also found that HSP70 induction by γ-rays was increased following GDA treatment (shown at 1 kGy). We suppose that the GDA-induced HSP70 can be involved in elimination of detrimental radiation effects that ultimately results in growth stimulation. On the other hand, the increase in phenotypic variation, when HSP90 function was impaired, confirms the supposition that the chaperone may control the concealment of cryptic genetic alterations and the developmental stability. In general, these results demonstrate that HSP90 may interface the stress response and phenotypic expression of genetic alterations induced by irradiation.

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.

Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak.

PubMed

Dauber, I M; Pluss, W T; VanGrondelle, A; Trow, R S; Weil, J V

1985-08-01

Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. We tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. We calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability we normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. We measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity we compared hydrostatic and high-dose thiourea edema. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 X 10-4 vs. 7.6 +/- 0.9 X 10-4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 X 10-4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity we compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. We conclude that a noninvasive double radioisotope measurement of pulmonary vascular protein leak, employing external counting techniques and a simplified method of calculation, is specific for lung injury and is also sensitive enough to detect lung injury insufficient to produce detectable pulmonary edema.

Atomic bomb health benefits.

PubMed

Luckey, T D

2008-01-01

Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment.

Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study

PubMed Central

Rosenblad, Carl; af Edholm Arvidsson, Karolina; Wictorin, Klas; Keywood, Charlotte; Shankar, Bavani; Lowe, David A.; Björklund, Anders; Widner, Håkan

2015-01-01

In advanced stages of Parkinson’s disease, serotonergic terminals take up l-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of l-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks l-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against l-DOPA-induced dyskinesias in patients with Parkinson’s disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of l-DOPA (Sinemet®) in 22 patients with Parkinson’s disease (16 male/six female; 66.6 ± 8.8 years old) with l-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson’s Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of l-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [–1.02(1.49); P = 0.004] and Rush Dyskinesia Rating Scale [–0.15(0.23); P = 0.003]; and maximum Clinical Dyskinesia Rating Scale score [–1.14(1.59); P = 0.005]. The post hoc analysis confirmed these results and also showed an antidyskinetic effect of 7.5 mg eltoprazine. Unified Parkinson’s Disease Rating Scale part III scores did not differ between the placebo and eltoprazine treatments. The most frequent adverse effects after eltoprazine were nausea and dizziness. It can be concluded that a single dose, oral treatment with eltoprazine has beneficial antidyskinetic effects without altering normal motor responses to l-DOPA. All doses of eltoprazine were well tolerated, with no major adverse effects. Eltoprazine has a favourable risk-benefit and pharmacokinetic profile in patients with Parkinson’s disease. The data support further clinical studies with chronic oral eltoprazine to treat l-DOPA-induced-dyskinesias. PMID:25669730

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.

Effect of feeding isolates of anaerobic fungus Neocallimastix sp. CF 17 on growth rate and fibre digestion in buffalo calves.

PubMed

Paul, Shyam S; Deb, Sitangshu M; Punia, Balbir S; Das, Kalyan S; Singh, Ghansham; Ashar, Manisha N; Kumar, Rajiv

2011-06-01

In this investigation, the effects of feeding encapsulated cells (rhizomycelia and zoospores) of a fibrolytic isolate from an anaerobic fungus (Neocallimastix sp. CF 17) on nutrient digestion, ruminal fermentation, microbial populations, enzyme profile and growth performance were evaluated in buffaloes. In three in vitro studies, the true digestibility of wheat straw was increased after addition of CF 17 to buffalo rumen fluid (p < 0.05). In Exp. 1, three groups of six buffaloes each (initial BW [body weight] 148 +/- 12.0 kg) were allotted to three dosing regimes: Group 1 received 200 ml of liquid culture of Neocallimastix sp. CF 17 (about 10(6) TFU [thallus-forming units]/ml); Group 2 received an encapsulated culture of the same fungi prepared from 200 ml liquid culture; Group 3: received 200 ml of autoclaved culture (Control). The supplementations were given weekly for four weeks (on days 1,7, 14 and 21). During the dosing period, the average daily gain of Group 2 was higher than in the Control group (444 g/d compared with 264 g/d; p < 0.05). Furthermore, the digestibility of organic matter increased in Group 1 and 2 compared with the Control (64.8, 64.0 and 60.4% respectively; p < 0.05), resulting in an increase in the total digestible nutrient (TDN) percent of ration (p < 0.05). But these effects disappeared post-dosing. There were also an increase in concentration of volatile fatty acids, trichloroacetic acid precipitable N and number of fibrolytic microbes in the rumen during the dosing period (p < 0.05), but these effects declined post-dosing. Results of Exp 2., where the encapsulated culture was applied at intervals of 4 d or 8 d for 120 d, showed that a shorter dosing frequency did not improve growth performance or feed intake. However, independent of the dosing frequency the growth rate of both groups fed the encapsulated culture were about 20% higher than in the Control group (p < 0.05). The present study showed that encapsulated fungi have a high potential to be used as feed additive at the farmers' level and that weekly dosing can increase growth performance of wheat straw based diets.

Experimental feeding of DDE and PCB to female big brown bats (Eptesicus fuscus). [1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene

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

Clark, D.R. Jr.; Prouty, R.M.

Twenty-two female big brown bats (Eptesicus fuscus) were collected in a house attic in Montgomery County, Maryland. Seventeen were fed mealworms (Tenebrio molitor larvae) that contained 166 ppM DDE; the other five were fed uncontaminated mealworms. After 54 days of feeding, six dosed bats were frozen and the remaining 16 were starved to death. In a second experiment, 21 female big brown bats were collected in a house attic in Prince Georges County, Maryland. Sixteen were fed mealworms that contained 9.4 ppM Aroclor 1254 (PCB). After 37 days, two bats had died, four dosed bats were frozen, and the remainingmore » 15 were starved to death. Starvation caused mobilization of stored residues. After the feeding periods, average weights of all four groups (DDE-dosed, DDE control, PCB-dosed, PCB control) had increased. However, weights of DDE-dosed bats had increased significantly more than those of their controls, whereas weights of PCB-dosed bats had increased significantly less than those of their controls. During starvation, PCB-dosed bats lost weight significantly more slowly than controls. Because PCB levels in dosed bats resembled levels found in some free-living big brown bats, PCBs may be slowing metabolic rates of some free-living bats. It is not known how various common organochlorine residues may affect metabolism in hibernating bats.« less

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

NASA Astrophysics Data System (ADS)

Li, X. Allen; Wang, Jian Z.; Stewart, Robert D.; Di Biase, Steven J.

2003-09-01

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

Aripiprazole maintenance increases smoked cocaine self-administration in humans

PubMed Central

Rubin, Eric; Foltin, Richard W.

2011-01-01

Rationale Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence. Objective This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D2 receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers. Methods In order to achieve steady-state concentrations, participants (n=8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose–response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance. Sessions comprised a “sample” trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00. Results Cocaine’s reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo. Conclusions These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence. PMID:21373790

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

Harrison, F.L.; Rice, D.W. Jr.; Moore, D.H.

Traditional bioassays are unsuitable for assessing sublethal effects of low levels of radioactivity because mortality and phenotypic responses are not anticipated. We compared the usefulness of chromosomal aberration (CA) and sister chromatid exchange (SCE) induction as measures of low-level radiation effects in a sediment-dwelling marine worm, Neanthes arenaceodentata. Newly hatched larvae were exposed to two radiation exposure regimes. Groups of 100 larvae were exposed to either x rays delivered at high dose rates (0.7 Gy min/sup -1/) or to /sup 60/Co gamma rays delivered at low dose rates (4.8 X 10/sup -5/ to 1.2 X 10/sup -1/ Gy h/sup -1/).more » After irradiation, the larvae were exposed to 3 X 10/sup -5/M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h (/sup 60/Co-irradiated larvae). Slides of larval cells were prepared for observation of CAs and SCEs. Frequencies of CAs were determined in first division cells; frequencies of SCEs were determined in second division cells. Results from x-ray irradiation indicated that dose-related increases occur in chromosome and chromatid deletions, but an x-ray dose greater than or equal to 2 Gy was required to observe a significant increase. Worm larvae receiving /sup 60/Co irradiation showed elevated SCE frequencies; a significant increase in SCE frequency was observed at 0.6 Gy. 49 references, 2 figures.« less

Wood Sawdust/Natural Rubber Ecocomposites Cross-Linked by Electron Beam Irradiation

PubMed Central

Manaila, Elena; Stelescu, Maria Daniela; Craciun, Gabriela; Ighigeanu, Daniel

2016-01-01

The obtaining and characterization of some polymeric eco-composites based on wood sawdust and natural rubber is presented. The natural rubber was cross-linked using the electron beam irradiation. The irradiation doses were of 75, 150, 300 and 600 kGy and the concentrations of wood sawdust were of 10 and 20 phr, respectively. As a result of wood sawdust adding, the physical and mechanical properties such as hardness, modulus at 100% elongation and tensile strength, showed significant improvements. The presence of wood sawdust fibers has a reinforcing effect on natural rubber, similar or better than of mineral fillers. An increase in the irradiation dose leads to the increasing of cross-link density, which is reflected in the improvement of hardness, modulus at 100% elongation and tensile strength of blends. The cross-linking rates, appreciated using the Flory-Rehner equation, have increased with the amount of wood sawdust in blends and with the irradiation dose. Even if the gel fraction values have varied irregularly with the amount of wood sawdust and irradiation dose it was over 90% for all blends, except for the samples without wood sawdust irradiated with 75 kGy. The water uptake increased with increasing of fiber content and decreased with the irradiation dose. PMID:28773626

Wood Sawdust/Natural Rubber Ecocomposites Cross-Linked by Electron Beam Irradiation.

PubMed

Manaila, Elena; Stelescu, Maria Daniela; Craciun, Gabriela; Ighigeanu, Daniel

2016-06-23

The obtaining and characterization of some polymeric eco-composites based on wood sawdust and natural rubber is presented. The natural rubber was cross-linked using the electron beam irradiation. The irradiation doses were of 75, 150, 300 and 600 kGy and the concentrations of wood sawdust were of 10 and 20 phr, respectively. As a result of wood sawdust adding, the physical and mechanical properties such as hardness, modulus at 100% elongation and tensile strength, showed significant improvements. The presence of wood sawdust fibers has a reinforcing effect on natural rubber, similar or better than of mineral fillers. An increase in the irradiation dose leads to the increasing of cross-link density, which is reflected in the improvement of hardness, modulus at 100% elongation and tensile strength of blends. The cross-linking rates, appreciated using the Flory-Rehner equation, have increased with the amount of wood sawdust in blends and with the irradiation dose. Even if the gel fraction values have varied irregularly with the amount of wood sawdust and irradiation dose it was over 90% for all blends, except for the samples without wood sawdust irradiated with 75 kGy. The water uptake increased with increasing of fiber content and decreased with the irradiation dose.

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.

Pharmacology of saccadic eye movements in man. 1. Effects of the benzodiazepine receptor ligands midazolam and flumazenil.

PubMed

Ball, D M; Glue, P; Wilson, S; Nutt, D J

1991-01-01

A paradigm for assessing benzodiazepine receptor sensitivity was developed using intravenous midazolam in normal volunteers. After administration of incremental doses of midazolam, alterations in saccadic eye movement parameters and psychological self ratings were assessed. Significant changes included dose-dependent slowing of peak velocity, peak acceleration, peak deceleration, reduced saccade acceleration/deceleration ratio and saccade accuracy, and increased sedation self-ratings. Changes in saccade variables and sedation ratings were significantly correlated, and also correlated with plasma midazolam concentrations. No significant changes were seen in saccade latency or anxiety self-ratings. Pharmacological specificity of these changes was demonstrated by their reversal with the benzodiazepine antagonist flumazenil. This challenge paradigm appears to be a sensitive means of assessing benzodiazepine receptor function in man.

Low- and high-dose laser irradiation effects on cell migration and destruction

NASA Astrophysics Data System (ADS)

Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

2018-02-01

Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

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